Conditions: Urothelial Carcinoma Bladder Cancer Transitional Cell Carcinoma
Keywords: nab-paclitaxel gemcitabine
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 3
Healthy volunteers: no

Brief summary:
The purpose of this trial is to determine the benefit of the combination of nab-paclitaxel plus gemcitabine given for 6 cycles, followed by maintenance nab-paclitaxel alone, in patients with cisplatin-ineligible or cisplatin-incurable advanced urothelial carcinoma (UC).

Detailed description:
This open-label, non-randomized phase II trial evaluates the efficacy and toxicity of first-line treatment with a combination of gemcitabine and nab-paclitaxel, followed by maintenance therapy with nab-paclitaxel alone in patients with metastatic or locally advanced unresectable urothelial cancer. Two groups of patients are eligible: (1) patients who are poor candidates for treatment with cisplatin, and (2) patients with visceral metastases who are incurable and unlikely to derive long-term benefit from treatment with cisplatin-based regimens. Eligible patients will receive a minimum of 3 cycles and up to 6 cycles of treatment with the gemcitabine/nab-paclitaxel combination. Patients having an objective response or stable disease will continue maintenance treatment with single-agent nab-paclitaxel until disease progression, intolerable toxicity, or patient decision to discontinue treatment. Up to 55 patients are planned for enrollment.

Arms:
arm 1: Induction Phase: nab-paclitaxel (125 mg/m²) and gemcitabine (1000 mg/m²) by IV infusion on Days 1 and 8 of each 21-day cycle. Responding or stable patients will be treated with a minimum of 3 cycles and up to 6 cycles before starting the single agent maintenance therapy.

Maintenance Phase: Patients completing 3-6 cycles of induction therapy with an objective response (complete or partial response) or stable disease will continue treatment with single agent nab-paclitaxel (260 mg/m²) by IV infusion every 21 days) until disease progression, intolerable toxicity or patient decision to discontinue treatment.

Interventions: intervention 1: nab-paclitaxel intervention 2: Gemcitabine
Intervention descriptions: intervention 1: Induction: 125 mg/m² by intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle for 3 to 6 cycles to be given with Gemcitabine.

Maintenance: single agent nab-paclitaxel (260 mg/m²) by IV infusion every 21 days) until disease progression, intolerable toxicity or patient decision to discontinue treatment. intervention 2: Induction: 1000 mg/m²) by IV infusion on Days 1 and 8 of each 21-day cycle for 3 to 6 cycles.

Protocol document:
Prot_SAP_000.pdf: 
 
C O N FI D E N TI A L  
T his  d o c u m e nt is  c o nfi d e nti al  a n d is t h e  pr o p ert y  of t h e  S C RI  D e v el o p m e nt I n n o v ati o ns,  L L C.   N o  p art  of t his 
d o c u m e nt  m a y  b e tr a ns mitt e d, r e pr o d u c e d,  p u blis h e d,  or  us e d  b y  ot h er  p ers o ns  wit h o ut  pri or  writt e n  a ut h oriz ati o n 
fr o m S C RI  D e v el o p m e nt I n n o v ati o ns,  L L C . 
G U  1 2 4  
A  P h as e II  St u d y  of  N a n o p a rti cl e  Al b u mi n -b o u n d  P a clit a x el  pl us  G e m cit a bi n e 
as  Fi rst -li n e  T h e r a p y f o r t h e  T r e at m e nt  of Cis pl ati n -i n eli gi bl e  o r  Cis pl ati n-
i n c u r a bl e  A d v a n c e d  U r ot h eli al  C a r ci n o m a  
S C RI  I N N O V A TI O N S S T U D Y  N U M B E R : 
 
G U  1 2 4  
 
S T U D Y  D R U G S:  
N a n o p arti cl e  al b u mi n -b o u n d  p a clit a x el  (n a b -p a clit a x el)  
G e m cit a bi n e   
S P O N S O R:  
S C RI  D e v el o p m e nt I n n o v ati o ns ,  L L C 
( S C RI I n n o v ati o ns) 
3 3 2 2  W est  E n d  A v e n u e ,  S uit e  9 0 0  
N as h vill e,  T N   3 7 2 0 3  
1- 8 7 7 -M Y - 1-S C RI  
as ks ar a h @s cr es e ar c h. n et  
 
S T U D Y  C O -C H AI R S: 
J o h n  H ai ns w ort h, M D  
S ar a h  C a n n o n  R e s e ar c h I nstit ut e    
3 3 2 2  W est  E n d  A v e n u e ,  S uit e  9 0 0  
N as h vill e,  T N   3 7 2 0 3  
6 1 5 -3 2 9 -7 2 7 4  
 
 
G ur u  S o n p a v d e,  M D  
U ni v ersit y  of  Al a b a m a  at  Bir mi n g h a m  
1 7 2 0  2 n d A v e  S o ut h,  N P  2 5 4 0  
Bir mi n g h a m,  A L  3 5 2 9 4 -3 5 0 0  
2 0 5 -9 7 5 -2 9 1 4  
D A T E  FI N A L:  
0 2  M a y  2 0 1 6  
 


 
 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2  of  6 9  
 
Cli ni c al  St u d y  St at e m e nt  of  C o m pli a n c e  
A  P h as e II  St u d y  f o r usi n g  N a n o p a rti cl e  Al b u mi n -b o u n d  P a clit a x el  pl us 
G e m cit a bi n e  as  Fi rst -li n e  T h e r a p y f o r  Cis pl ati n-i n eli gi bl e  o r  Cis pl ati n-
i n c u r a bl e  A d v a n c e d  U r ot h eli al  C a r ci n o m a  
 
 
 T his  cli ni c al  st u d y s h all  b e  c o n d u ct e d i n  c o m pli a n c e  wit h t h e  p r ot o c ol,  as  r ef e r e n c e d  h e r ei n, 
a n d  all  a p pli c a bl e l o c al,  n ati o n al,  a n d i nt e r n ati o n al  r e g ul at o r y  r e q ui r e m e nts t o i n cl u d e,  b ut  n ot 
b e li mit e d t o:  
•   I nt e r n ati o n al  C o nf e r e n c e  o n  H a r m o nis ati o n (I C H)  G ui d eli n es  o n  G o o d  Cli ni c al 
P r a cti c e ( G C P)  
•   Et hi c al  p ri n ci pl es t h at  h a v e t h ei r  o ri gi ns i n t h e  D e cl a r ati o n  of  H elsi n ki   
•   F o o d  a n d  D r u g  A d mi nist r ati o n ( F D A)  C o d e  of  F e d e r al  R e g ul ati o n ( C F R):  
o   
Titl e  2 1 C F R  P a rt  5 0  &  4 5  C F R  P a rt  4 6,  P r ot e cti o n  of  H u m a n  S u bj e cts 
o   
Titl e  2 1 C F R  P a rt  5 4,  Fi n a n ci al  Dis cl os u r e  b y  Cli ni c al I n v esti g at o rs  
o   
Titl e  2 1 C F R  P a rt  5 6, I nstit uti o n al  R e vi e w  B o a r ds  
o   
Titl e  2 1 C F R  P a rt  3 1 2, I n v esti g ati o n al  N e w  D r u g  A p pli c ati o n 
o   
Titl e  4 5  C F R  P a rts  1 6 0,  1 6 2,  a n d  1 6 4,  H e alt h I ns u r a n c e  P o rt a bilit y  a n d 
A c c o u nt a bilit y  A ct ( HI P A A)   
 
As t h e  St u d y  C h ai r  a n d/ o r  P ri n ci p al I n v esti g at o r , I  u n d e rst a n d t h at  m y si g n at u r e  o n t h e 
p r ot o c ol  c o nstit ut es  m y  a g r e e m e nt  a n d  u n d e rst a n di n g  of  m y  r es p o nsi biliti es t o  c o n d u ct t h e 
cli ni c al st u d y  i n  a c c o r d a n c e t o t h e  p r ot o c ol  a n d  a p pli c a bl e  r e g ul ati o ns.   F u rt h e r m o r e, it 
c o nstit ut es  m y  u n d e rst a n di n g  a n d  a g r e e m e nt t h at  a n y  c h a n g es i niti at e d  b y  m ys elf,  wit h o ut 
p ri o r  a g r e e m e nt i n  w riti n g f r o m t h e  S p o ns o r, s h all  b e  d efi n e d  as  a  d e vi ati o n f r o m t h e  p r ot o c ol, 
a n d s h all  b e f o r m all y  d o c u m e nt e d  as s u c h.  
 


 
 
 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3  of  6 9  
Cli ni c al  St u d y  Si g n at u r e  A p p r o v al  P a g e  
A  P h as e II  St u d y  f o r usi n g  N a n o p a rti cl e  Al b u mi n -b o u n d  P a clit a x el  pl us 
G e m cit a bi n e  as  Fi rst -li n e  T h e r a p y f o r  Cis pl ati n-i n eli gi bl e  o r  Cis pl ati n-
i n c u r a bl e  A d v a n c e d  U r ot h eli al  C a r ci n o m a  
 
S C RI I N N O V A T I O N S  S T U D Y  N U M B E R : 
 
G U  1 2 4  
S T U D Y  D R U G ( S): 
N a n o p arti cl e  Al b u mi n -b o u n d  P a clit a x el  (n a b -
p a clit a x el)  
G e m cit a bi n e    
D A T E  FI N A L:  
0 2  M a y  2 0 1 6  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _   
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _          _ _ _ _ _ _ _ _ _ _ _ _ _ _  
St u d y  C o -C h ai r  
  
St u d y  C o -C h ai r  Si g n at u r e  
 
D at e  
 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _  
St u d y  C o -C h ai r  
 
St u d y  C o -C h ai r  Si g n at u r e  
 
D at e  
 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _   
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _          _ _ _ _ _ _ _ _ _ _ _ _ _ _  
S p o ns o r  R e p r e s e nt ati v e  
S C RI   D e v el o p m e n t I n n o v ati o ns,  L L C 
S p o ns o r  R e p r e s e nt ati v e  Si g n at u r e  
 
D at e  
 
 
 
J o h n  H ai ns w ort h,  M D.  
S h e et al  K h e d k ar,  M D.  
G ur u  S o n p a v d e,  M D  


 
 
 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4  of  6 9  
 
Cli ni c al  St u d y  P ri n ci p al I n v esti g at o r  Si g n at u r e  F o r m  
A  P h as e II  St u d y f o r  usi n g  N a n o p a rti cl e  Al b u mi n -b o u n d  P a clit a x el  pl us 
G e m cit a bi n e  as  Fi rst -li n e  T h e r a p y f o r  Cis pl ati n-i n eli gi bl e  o r  Cis pl ati n-
i n c u r a bl e  A d v a n c e d  U r ot h eli al  C a r ci n o m a 
 
S C RI  I N N O V A TI O N S  S T U D Y  N U M B E R:  
 
 G U  1 2 4  
D A T E  FI N A L:  
0 2  M a y  2 0 1 6  
 
B y si g ni n g t his  pr ot o c ol  a c c e pt a n c e  p a g e, I  c o nfir m I  h a v e r e a d,  u n d erst a n d,  a n d  a gr e e t o  c o n d u ct t h e 
st u d y i n  a c c or d a n c e  wit h t h e  c urr e nt  pr ot o c ol. 
 
 
J o h n  H ai ns w ort h,  M D 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _             _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _      _ _ _ _ _ _ _  
P ri n ci p al I n v esti g at o r  N a m e  
( Pl e as e  Pri nt) 
 
P ri n ci p al I n v esti g at o r  Si g n at u r e  
 
D at e  
 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  _   
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _   
_ _ _ _ _ _ _  
P ri n ci p al I n v esti g at o r  N a m e  
( Pl e as e  Pri nt) 
 
P ri n ci p al I n v esti g at o r  Si g n at u r e   
D at e  
 
Pl e as e r et ai n  a  c o p y  of t his  p a g e f or  y o ur st u d y fil es  a n d r et ur n t h e  ori gi n al si g n e d  a n d  d at e d 
f or m t o: 
 
S C RI  D e v el o p m e nt I n n o v ati o ns ,  L L C 
3 3 2 2  W est  E n d  A v e n u e,  S uit e  9 0 0 
Att n:   G U  1 2 4  St u d y  T e a m   
N as h vill e,  T N  3 7 2 0 3 
G ur u  S o n p a v d e,  M D  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5  of  6 9  
G U  1 2 4   P R O T O C O L S Y N O P SI S  
Titl e  of  St u d y : 
A  P h as e II  St u d y f or  usi n g  N a n o p arti cl e  Al b u mi n -b o u n d  P a clit a x el  pl us  G e m cit a bi n e  as 
First -li n e  T h er a p y f or  Cis pl ati n-i n eli gi bl e  or  Cis pl ati n-i n c ur a bl e  Ad v a n c e d  Ur ot h eli al 
C ar ci n o m a  
S C RI  I n n o v ati o ns 
St u d y  N u m b e r : 
G U  1 2 4  
S p o ns o r:  
S C RI  D e v el o p m e nt I n n o v ati o ns ,  L L C –  N as h vill e  - T N  
St u d y  D u r ati o n:  
T h e t ot al  d ur ati o n  of t h e  st u d y is  pl a n n e d t o  b e 3 6  m o nt hs   
P h as e  of  St u d y :  II 
St u d y  C e nt e r s: 
T his  st u d y will  b e  c o n d u ct e d  i n t w el v e sit e s. 
N u m b e r  of 
P ati e nts:  
U p t o  5 5  p ati e nts  ar e  pl a n n e d t o  b e  e nr oll e d i n t his st u d y.  
O bj e cti v es:   
P ri m a r y  O bj e cti v e  
T h e  pri m ar y  o bj e cti v e  of t his  st u d y is t o  e v al u at e t h e  effi c a c y  of first -li n e tr e at m e nt  wit h 
n a b -p a clit a x el -g e m ci t a bi n e i n  p ati e nts  wit h  a d v a n c e d  ur ot h eli al  c ar ci n o m a  w h o  ar e  eit h er 
p o or  c a n di d at es f or  cis pl ati n -c o nt ai ni n g  c h e m ot h er a p y  or  h a v e  vis c er al  m et a st as e s  a n d  ar e 
cis pl ati n -i n c ur a bl e.   T h e  pri m ar y  e n d p oi nt is t h e pr o gr essi o n -fr e e s ur vi v al ( P F S) r at e  at  6 
m o nt h s  aft er t h e st art  of tr e at m e nt.  
 
S e c o n d a r y  O bj e cti v e s 
T h e s e c o n d ar y  o bj e cti v es  of t his st u d y  ar e t o  e v al u at e t h e  s af et y,  o bj e cti v e r es p o ns e r at e 
(O R R ), c o m pl et e r es p o ns e ( C R ) r at e,  a n d o v er all s ur vi v al ( O S ) wit h t h e  n a b -p a clit a x el -
g e m cit a bi n e  c o m bi n ati o n.  
 
E x pl o r at o r y  o bj e cti v es  
T h e  e x pl or at or y  o bj e cti v es  ar e t o  e v al u at e  ar c hi v al t u m or tiss u e  b y i m m u n o hist o c h e mistr y 
(I H C) f or  S P A R C  a n d  g e n e  e x pr essi o n  a n d s e q u e n ci n g  of  a  p a n el  of  g e n es t o  e x a mi n e t h eir 
ass o ci ati o n  wit h  P F S,  O R R  a n d  O S  
St u d y  D esi g n : 
T his is  a n  o p e n -l a b el  n o n-r a n d o mi z e d P h as e II st u d y t o  d et er mi n e t h e  b e n efit  of t h e 
c o m bi n ati o n  of  n a b -p a clit a x el  a n d  g e m cit a bi n e  gi v e n f or  6  c y cl es, f oll o w e d  b y  m ai nt e n a n c e 
n a b -p a clit a x el  al o n e,  i n  p ati e nts  wit h  cis pl ati n-i n eli gi bl e or  cis pl ati n -i n c ur a bl e a d v a n c e d 
ur ot h eli al  c ar ci n o m a ( U C ).   
St u d y  D r u gs, 
D os es,  a n d  M o d es 
of  A d mi nist r ati o n:  
I n d u cti o n  p h as e :  All  p ati e nts i n t his st u d y  will r e c ei v e  n a b-p a clit a x el ( 1 2 5  m g/ m 2)  a n d 
g e m cit a bi n e ( 1 0 0 0  m g/ m 2)  b y I V i nf usi o n  o n  D a y  1  a n d  D a y  8  of  e a c h  2 1-d a y  c y cl e.  
R es p o n di n g  or st a bl e  p ati e nts  will  b e tr e at e d  wit h  a  mi ni m u m  of  3  c y cl e s  a n d  u p t o  6  c y cl es 
b ef or e st arti n g t h e  si n gl e  a g e nt  m ai nt e n a n c e t h er a p y.  D os es  of  g e m cit a bi n e  a n d  n a b -
p a clit a x el s h o ul d  b e r e c al c ul at e d if t h er e is  a  ≥  1 0 %  c h a n g e i n t h e  p ati e nt’s  b o d y  w ei g ht 
si n c e t h e  pr e vi o us  c al c ul ati o n.  
M ai nt e n a n c e  p h as e :  P ati e nts  w h o  h a v e o bj e cti v e r es p o ns e ( C R  or  P R)  or  S D  aft er 
c o m pl eti n g  3 -6  c y cl es  of  i n d u cti o n t h er a p y  wit h  n a b-p a clit a x el -g e m cit a bi n e  will  c o nti n u e 
tr e at m e nt  wit h si n gl e  a g e nt  n a b-p a clit a x el ( 2 6 0  m g/ m 2 I V  e v er y  2 1  d a ys)  u ntil  dis e as e 
pr o gr essi o n, i nt ol er a bl e t o xi cit y  or  p ati e nt  d e cisi o n t o  dis c o nti n u e tr e at m e nt.   P ati e nts  w h o 
h a v e  S D  or  r es p o n d t o  n a b-p a clit a x el -g e m cit a bi n e  b ut  c a n n ot  c o m pl et e  6  c y cl e s  d u e t o  p o or 
t ol er a n c e  m a y s wit c h t o  m ai nt e n a n c e tr e at m e nt  wit h si n gl e-a g e nt  n a b -p a clit a x el  aft er 
c o m pl eti n g  a  mi ni m u m  of  3  c y cl es  of  c o m bi n ati o n t h er a p y.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6  of  6 9  
 
G U  1 2 4   PR O T O C O L  S Y N O P SI S  
I n cl usio n  C rit e ri a:  
1.   Hist ol o gi c all y  c o nfir m e d  di a g n osis  of  U C t h at is  eit h er  m et a st ati c ( a n y  N +  M 1)  or l o c all y 
a d v a n c e d  a n d  u nr es e ct a bl e ( T 4 b N 0).  A  c o m p o n e nt  of  ur ot h eli al (tr a nsiti o n al  c ell) 
c ar ci n o m a is r e q uir e d.  
2.   T w o  gr o u ps  of  p ati e nts  ar e  eli gi bl e:   
a.   P o or  c a n di d at es f or  cis pl ati n -b as e d  c h e m ot h er a p y,  b as e d  o n t h e  pr es e n c e  of 
≥  1 t h e f oll o wi n g:   
•   Gl o m er ul ar filtr ati o n r at e  of  3 0 -6 0  ml/ mi n ( C o c k cr oft -G a ult f or m ul a)  
•   E C O G  p erf or m a n c e st at us  s c or e  of  2 ( A p p e n di x  A ) 
•   H e ari n g l o ss (tr o u bl e  c o m m u ni c ati n g  wit h  h e ari n g  ai ds  or  h e ari n g l oss 
at  ≤  3  K H z)  
•   Gr a d e  ≥ 3  h e art f ail ur e ( N Y H A  A p p e n di x  B )  
•   A g e  ≥ 8 0  y e ars  
•   Ot h er  c o n c urr e nt ill n ess  w hi c h  m a y  m a k e t h e  p ati e nt  a  p o or  c a n di d at e 
f or r e c ei vi n g  cis pl ati n. 
N ot e:  E nr oll m e nt  of  p ati e nts  wit h  2  or  m or e  of t h es e  crit eri a s h o ul d  o c c ur 
o nl y  aft er  c ar ef ul  c o nsi d er ati o n  b y t h e tr e ati n g  p h ysi ci a n r e g ar di n g t h e 
p ati e nt’s  a bilit y t o t ol er at e  c o m bi n ati o n  c h e m ot h er a p y.  
O R  
b.   P o or  pr o g n osis  a n d  d efi n e d  as  cis pl ati n -i n c ur a bl e  d u e t o t h e  pr es e n c e  of 
m et ast asis t o  at l e ast  o n e  vis c er al sit e (t h es e  p ati e nts  ar e  n ot r e q uir e d t o 
h a v e  a n y  of t h e  cis pl ati n -i n eli gi bilit y  crit eri a).  
•   E C O G  p erf or m a n c e st at us  s c or e  of  0,  1,  or  2 ( A p p e n di x  A ). 
3.   M e as ur a bl e  dis e as e  b y  R es p o ns e  E v al u ati o n  Crit eri a i n  S oli d  T u m ors ( R E CI S T)  v ersi o n 
1. 1 ( A p p e n di x  E ). 
4.   P ati e nts  wit h  pr e vi o usl y tr e at e d  br ai n  m et ast a s es  ar e  eli gi bl e if   
c.   Tr e at m e nt  w a s  c o m pl et e d  ≥  4  w e e ks  pri or t o st u d y tr e at m e nt,   
d.   N e ur ol o gi c s y m pt o ms  ar e  mi ni m al  a n d st a bl e  d uri n g t h e  pr e c e di n g  4  w e e ks, 
a n d  
e.   M ai nt e n a n c e  d e x a m et h a s o n e is  n ot r e q uir e d.  
5.   A n y  pr e -e xisti n g  p eri p h er al  n e ur o p at h y  m ust  b e  <  Gr a d e  2.  
6.   A d e q u at e  h e m at ol o gi c f u n cti o n  at  b as eli n e,  d efi n e d  as:  
-   A bs ol ut e  n e utr o p hil  c o u nt ( A N C)  ≥ 1 5 0 0/ μ L  
-   H e m o gl o bi n ( H g b)  ≥  9  g/ d L ( us e  of  gr o wt h f a ct or  or r e d  bl o o d  c ell 
tr a nsf usi o n t o  a c hi e v e t his l e v el is  all o w e d) 
-   Pl at el ets  > 1 0 0, 0 0 0/ µ L  
7.   A d e q u at e li v er f u n cti o n  at  b as eli n e,  d efi n e d  as:  
-   Bilir u bi n  ≤ 1. 5  m g/ d L  
-   Al a ni n e  a mi n otr a nsf er as e ( A L T)  a n d  as p art at e  a mi n otr a nsf er as e ( A S T)  ≤ 
2. 5  x  u p p er li mit  of  n or m al [ U L N] ( u nl ess  b o n e  m arr o w  m et ast as es  ar e 
pr es e nt i n t h e  a bs e n c e  of li v er  m et ast asis),  ≤ 5  x  U L N if li v er  m et ast as es  ar e 
pr es e nt  
8.   C al c ul at e d  cr e ati ni n e  cl e ar a n c e  ≥ 3 0  m L/ mi n ut e ( C o c k cr oft -G a ult f or m ul a)  
 
 
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  7  of  6 9  
G U  1 2 4  P R O T O C O L  S Y N O P SI S  
I n cl usi o n 
C rit e ri a:  
9.   M al e  p ati e nts  wit h f e m al e  p art n ers  of  c hil d b e ari n g  p ot e nti al  a n d  w o m e n  p ati e nts  of 
c hil d b e ari n g  p ot e nti al  ar e r e q uir e d t o  us e t w o f or ms  of  a c c e pt a bl e  c o ntr a c e pti o n, 
i n cl u di n g  o n e  b arri er  m et h o d,  d uri n g t h eir p arti ci p ati o n i n t h e st u d y  a n d f or  3  m o nt hs 
f oll o wi n g l ast  d os e  of st u d y  dr u g( s).   M al e  p ati e nts  m ust  als o r efr ai n fr o m  d o n ati n g 
s p er m  d uri n g t h eir  p arti ci p ati o n i n t h e st u d y ( A p p e n di x  C).  
1 0.   W o m e n  of  c hil d b e ari n g  p ot e nti al ( W o C B P)  m ust  h a v e  a  n e g ati v e s er u m  or  uri n e  β -
h C G  pr e g n a n c y t e st  p erf or m e d  wit hi n  7 2  h o urs  pri or t o st art  of tr e at m e nt  a n d  m ust  us e 
t w o f or ms  of  a c c e pt a bl e  c o ntr a c e pti o n, i n cl u di n g  o n e  b arri er  m et h o d,  c o ntr a c e pti v e 
m et h o d  d uri n g tr e at m e nt  a n d f or  3  m o nt hs  aft er  c o m pl eti n g tr e at m e nt. If  a  w o m a n 
b e c o m e s  pr e g n a nt  or s us p e cts  s h e is  pr e g n a nt  w hil e  p arti ci p ati n g i n t his st u d y, s h e 
m ust  a gr e e t o i nf or m  h er tr e ati n g  p h ysi ci a n i m m e di at el y.  
1 1.   A g e  ≥ 1 8  y e ars.  
1 2.   Willi n g n e ss  a n d  a bilit y t o  c o m pl y  wit h  st u d y  a n d f oll o w -u p  pr o c e d ur es.  
1 3.   A bilit y t o  u n d erst a n d t h e  n at ur e  of t his  st u d y  a n d  gi v e  writt e n i nf or m e d  c o ns e nt.  
E x cl usi o n 
C rit e ri a:  
1.   Pr e vi o us s yst e mi c  c h e m ot h er a p y f or  U C,  wit h t h e  e x c e pti o n  of  p eri o p er ati v e 
( n e o a dj u v a nt  or  a dj u v a nt) tr e at m e nt  or tr e at m e nt  wit h  c o n c urr e nt  c h e m o-r a di ati o n f or 
l o c all y  a d v a n c e d  dis e as e.   All  of t h e s e tr e at m e nts  m ust  h a v e  b e e n  c o m pl et e d  >  1  y e ar 
pr e vi o usl y.    
2.   Pr es e n c e  of s m all -c ell  or s ar c o m at oi d  c o m p o n e nt i n t u m or  hist ol o g y  
3.   W o m e n  w h o  ar e  pr e g n a nt  or  br e ast -f e e di n g 
4.   M aj or s ur gi c al  pr o c e d ur es  ≤ 2 8  d a ys  of  b e gi n ni n g st u d y  dr u g,  or  mi n or s ur gi c al 
pr o c e d ur es  ≤ 7  d a ys.   N o  w aiti n g r e q uir e d f oll o wi n g  p ort - a-c at h  pl a c e m e nt.  
5.   A n y  of t h e f oll o wi n g  c ar di a c  dis e as es  c urr e ntl y  or  wit hi n t h e l ast  6  m o nt hs:  
•   Q T c i nt er v al  > 4 8 0  ms ( p er  i nstit uti o n al st a n d ar d)  o n s cr e e ni n g  el e ctr o c ar di o gr a m 
( E C G)  
•   U nst a bl e  a n gi n a  p e ct oris  
•   A c ut e  m y o c ar di al i nf ar cti o n  
•   C o n d u cti o n  a b n or m alit y  n ot  c o ntr oll e d  wit h  p a c e m a k er  or  m e di c ati o n  
•   Si g nifi c a nt  v e ntri c ul ar  or s u pr a v e ntri c ul ar  arr h yt h mi a s ( p ati e nts  wit h  c hr o ni c r at e -
c o ntr oll e d  atri al  fi brill ati o n i n t h e  a bs e n c e  of  ot h er  c ar di a c  a b n or m aliti e s  ar e 
eli gi bl e)  
•   V al v ul ar  dis e as e  wit h si g nifi c a nt  c o m pr o mis e i n  c ar di a c f u n cti o n  
6.   I n a d e q u at ely  c o ntr oll e d  h y p ert e nsi o n (i. e., s yst oli c  bl o o d  pr ess ur e [ S B P]  ≥ 1 8 0  m m H g 
or  di ast oli c  bl o o d  pr ess ur e  [D B P ] ≥ 1 0 0  m m H g) ( p ati e nts  wit h  v al u e s  a b o v e t h es e 
l e v els  m ust  h a v e t h eir  bl o o d  pr ess ur e ( B P)  c o ntr oll e d  wit h  m e di c ati o n  pri or t o st arti n g 
tr e at m e nt). 
7.   C urr e ntl y r e c ei vi n g tr e at m e nt  wit h t h er a p e uti c  d os es  of  w arf ari n s o di u m.   H o w e v er,  a 
m a xi m u m  d ail y  d os e  of  1  m g  will  b e  p er mitt e d f or  p ort li n e  p at e n c y.   L o w  m ol e c ul ar 
w ei g ht  h e p ari n is  all o w e d.   
8.   S eri o us  a cti v e i nf e cti o n  at t h e ti m e  of tr e at m e nt,  or  a n ot h er s e ri o us  u n d erl yi n g  m e di c al 
c o n diti o n t h at  w o ul d i m p air t h e  a bilit y  of t h e  p ati e nt t o r e c ei v e  pr ot o c ol tr e at m e nt.  
9.   K n o w n  di a g n osis  of  h u m a n i m m u n o d efi ci e n c y  vir us,  h e p atitis  B,  or  h e p atitis  C  
(s cr e e ni n g f or t h es e  dis e a s es is  n ot r e q uir e d). 
1 0.   Pr es e n c e  of  ot h er  a c ti v e  c a n c ers,  or  hist or y  of tr e at m e nt f or i n v a si v e  c a n c er  ≤ 5  y e ars 
pr e vi o usl y.   P ati e nts  wit h  St a g e I  c a n c er  w h o  h a v e r e c ei v e d  d efi niti v e l o c al tr e at m e nt 
a n d  ar e  c o nsi d er e d  u nli k el y t o r e c ur  ar e  eli gi bl e.   All  p ati e nts  wit h  pr e vi o usl y tr e at e d i n 
sit u  c ar ci n o m a (i. e.,  n o n -i n v asi v e)  ar e  eli gi bl e,  as  ar e  p ati e nts  wit h  hist or y  of  n o n-
m el a n o m a s ki n  c a n c er.  
1 1.   Ps y c h ol o gi c al, f a mili al,  s o ci ol o gi c al,  or  g e o gr a p hi c al  c o n diti o ns t h at  d o  n ot  p er mit 
c o m pli a n c e  wit h t h e  pr ot o c ol.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  8  of  6 9  
G U  1 2 4  P R O T O C O L  S Y N O P SI S  
C o r r el ati v e 
T est i n g: 
If  a v ail a bl e, tu m or tiss u e fr o m  ar c hi v al  bi o psi es  will  b e  c oll e ct e d t o  b e  c e ntr all y  st u di e d i n 
t h e f ut ur e  wit h s e p ar at e f u n di n g.   P ot e nti al I H C st u di es  p erf or m e d  c e ntr all y  will i n cl u d e  b ut 
ar e  n ot li mit e d t o  s e cr et e d  pr ot ei n  a ci di c  a n d ri c h i n  c yst ei n e ( S P A R C ) e x pr essi o n.   G e n e 
e x pr essi n g  pr ofili n g  of t u m or tiss u e  usi n g  N a n ostri n g  or  ot h er si mil ar t e c h n ol o g y  m a y  als o 
b e  p erf or m e d.  
St atisti c al 
M et h o d ol o g y:  
T h e  p ur p os e  of t his  o p e n -l a b el  n o n-r a n d o mi z e d P h as e  II tri al is t o st u d y t h e  effi c a c y  a n d 
t o xi city  of t h e  g e m cit a bi n e/ n a b -p a clit a x el  c o m bi n ati o n f oll o w e d  b y  m ai nt e n a n c e si n gl e -
a g e nt  n a b -p a clit a x el  a s t h e first -li n e tr e at m e nt  of  p ati e nts  wit h  a d v a n c e d  U C. 
T w o  gr o u ps  of  p ati e nts  will  b e  eli gi bl e f or t his st u d y:   
1)  p ati e nts  w h o  ar e  c o nsi d er e d  p o or  c a n di d at es f or tr e at m e nt  wit h  cis pl ati n,  a n d   
2)  p ati e nts  wit h  vis c er al  m et a st as es,  w h o  ar e i n c ur a bl e  a n d  u nli k el y t o  d eri v e l o n g -t er m 
b e n efit fr o m tr e at m e nt  wit h  cis pl ati n -b as e d r e gi m e ns.  
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  9  of  6 9  
G U  1 2 4  C O N T A C T I N F O R M A TI O N  
S C RI  I n n o v ati o ns 
C o nt a ct I nf o r m ati o n:  
S C R I I n n o v ati o ns 
3 3 2 2  W est  E n d  A v e n u e,  S uit e  9 0 0  
N as h vill e,  T N   3 7 2 0 3  
1- 8 7 7 -M Y - 1-S C RI  
as ks ar a h @s cr es e ar c h. n et  
 
St u d y  C o -C h ai r : 
J o h n  H ai ns w ort h,  M D  
S ar a h  C a n n o n  R e s e ar c h I nstit ut e  
3 3 2 2  W est  E n d  A v e n u e,  S uit e  9 0 0  
N as h vill e,  T N   3 7 2 0 3  
1- 8 7 7 -M Y - 1-S C RI  
as ks ar a h @s cr es e ar c h. n et  
 
St u d y  C o -C h ai r  
G ur u  S o n p a v d e,  M D  
U ni v ersit y  of  Al a b a m a  at  Bir mi n g h a m  
1 7 2 0  2 n d A v e  S o ut h,  N P  2 5 4 0  
Bir mi n g h a m,  A L  3 5 2 9 4 -3 5 0 0  
2 0 5 -9 7 5 -2 9 1 4  
gs o n p a v d e @ u a b m c. e d u   
S af et y  D e pt.  P h o n e  # /  F a x  #:  
S af et y  D e pt.  E m ail:  
1 -6 1 5 -3 2 9 -7 3 5 8/ 1 -8 6 6 -8 0 7 -4 3 2 5  
C A N N. S A E @ S C RI -I n n o v ati o ns. c o m 
R e g ul at o r y  P h o n e  #    
R e g ul at o r y  E m ail:  
1 -8 7 7 -M Y -1 -S C RI   
S C RI R e g ul at or y @ S C RI -I n n o v ati o ns. n et 
S C RI  In n o v ati o ns  E n r oll m e nt  P h o n e  #:  
S C RI  I n n o v ati o ns E n r oll m e nt  F a x  #:  
S C RI I n n o v ati o ns  E n r oll m e nt  E m ail:  
1 -8 7 7 -M Y -1 -S C RI  
1- 8 6 6 -6 9 9 -0 2 5 8  
C A N N. S C RII n n o v ati o ns E nr @s cri -i n n o v ati o ns. c o m 
S o u r c e  D o c u m e nt ati o n  F a x #:  
S o u r c e  D o c u m e nt ati o n  E m ail:  
1 -8 5 5 -6 6 7 -3 7 1 3  
C A N N. O R C D at a @ h c a h e alt h c ar e. c o mt  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 0  of  6 9  
LI S T  O F  A B B R E VI A TI O N S  
A E  
A d v ers e  e v e nt  
A L P  
Al k ali n e  p h os p h at as e  
A L T  
Al a ni n e  a mi n otr a nsf er as e  
A N C  
A bs ol ut e  n e utr o p hil  c o u nt  
A S T   
As p art at e  a mi n otr a nsf er as e  
C B C  
C o m pl et e  bl o o d  c o u nt  
C B R   
Cli ni c al  b e n efit r at e  
C F R  
C o d e  of  F e d er al  R e g ul ati o ns  
CI  
C o nfi d e n c e i nt er v al  
C M P  
C o m pr e h e nsi v e  m et a b oli c  pr ofil e  
C R  
C o m pl et e  r es p o ns e/r e missi o n 
C r  Cl  
Cr e ati ni n e  cl e ar a n c e  
C T  
C o m p ut eri z e d t o m o gr a p h y  
E C G  
El e ctr o c ar di o gr a m  
E C O G   
E ast er n  C o o p er ati v e  O n c ol o g y  Gr o u p   
e C R F  
el e ctr o ni c  C as e  R e p ort  F or m  
F D A  
F o o d  a n d  Dr u g  A d mi nistr ati o n  
G C  
G e m cit a bi n e  pl us  cis pl ati n  
G C P  
G o o d  Cli ni c al  Pr a cti c e  
HI P A A  
H e alt h I ns ur a n c e  P ort a bilit y  a n d  A c c o u nt a bilit y  A ct  
I B 
I n v e sti g at or  Br o c h ur e 
I C F  
I nf or m e d  c o ns e nt f or m 
I C H 
I nt er n ati o n al  C o nf er e n c e  o n  H ar m o ni z ati o n 
I N R  
I nt er n ati o n al  N or m ali z e d  R ati o 
I R B 
I nstit uti o n al  R e vi e w  B o ar d 
I V  
I ntr a v e n o us 
M RI  
M a g n eti c r es o n a n c e i m a gi n g  
M V A C  
M et h otr e x a t e,  vi n bl a sti n e,  d o x or u bi ci n,  a n d  cis pl ati n 
N CI  C T C A E  
N ati o n al  C a n c er I nstit ut e  C o m m o n  T er mi n ol o g y  Crit eri a f or  A d v ers e  E v e nts  
N Y H A  
N e w  Y or k  H e art  Ass o ci ati o n  
O R  
O bj e cti v e r es p o ns e  
O R R  
O v er all r es p o ns e r at e  
O S  
O v er all s ur vi v al  
P D  
Pr o gr essi v e  dis e as e  
P F S 6  
6- m o nt h  pr o gr essi o n -fr e e s ur vi v al 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 1  of  6 9  
LI S T  O F  A B B R E VI A TI O N S ( c o nti n u e d)  
P F S  
Pr o gr essi o n -fr e e s ur vi v al 
P HI  
Pr ot e ct e d  h e alt h i nf or m ati o n  
P R  
P arti al r es p o ns e /r e missi o n 
P T  
Pr ot hr o m bi n ti m e  
R R  
R es p o ns e r at e  
S A E  
S eri o us  a d v ers e  e v e nt  
S A R  
S us p e ct e d  a d v er s e r e a cti o n  
S C RI  
S ar a h  C a n n o n  R e s e ar c h I nstit ut e  
S D  
St a bl e  dis e as e  
S P A R C  
S e cr et e d  pr ot ei n  a ci di c  a n d ri c h i n  c yst ei n e  
S U S A R  
S us p e ct e d  U n e x p e ct e d  S eri o us  A d v ers e  R e a cti o ns  
U C  
Ur ot h eli al  c ar ci n o m a  
U L N  
U p p er li mit  of  n or m al  
U S PI  
U S  P a c k a g e I ns ert  
W o C B P  
W o m e n  of  c hil d b e ari n g  p ot e nti al   


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 2  of  6 9  
T A B L E  O F  C O N T E N T S  
1.  
I N T R O D U C TI O N .................................................................................................  1 6 
1. 1  
B a c k gr o u n d ...........................................................................................................  1 6  
1. 2  
Tr e at m e nt f or  a d v a n c e d  ur ot h eli al  c ar ci n o m a i n  cis pl ati n -i n eli gi bl e  p ati e nts ......  1 7 
1. 3  
N a b -p a clit a x el  .......................................................................................................  1 7 
1. 3. 1  
N a b -p a clit a x el i n t h e  Tr e at m e nt  of  Ur ot h eli al  C ar ci n o m a  ....................................  1 8 
1. 4  
G e m cit a bi n e ...........................................................................................................  1 8 
1. 5  
R ati o n al e f or t h e  St u d y ..........................................................................................  1 8  
2.  
S T U D Y  O BJ E C TI V E S  .........................................................................................  1 9 
2. 1  
Pri m ar y  O bj e cti v e ..................................................................................................  1 9 
2. 2  
S e c o n d ar y  O bj e cti v es  ............................................................................................  1 9 
2. 3  
E x pl or at or y  o bj e cti v es ...........................................................................................  1 9  
3.  
S T U D Y  P A TI E N T  P O P U L A TI O N  A N D  DI S C O N TI N U A TI O N  ......................  1 9 
3. 1  
I n cl usi o n  Crit eri a ...................................................................................................  1 9 
3. 2  
E x cl usi o n  Crit eri a  ..................................................................................................  2 1 
3. 3  
Dis c o nti n u ati o n fr o m  St u d y  Tr e at m e nt .................................................................  2 2  
4.  
P A TI E N T  R E GI S T R A TI O N  ................................................................................  2 3 
5.  
S T U D Y  D E SI G N  ..................................................................................................  2 3 
5. 1  
Tr e at m e nt  Pl a n  ......................................................................................................  2 6 
5. 1. 1  
G e m cit a bi n e  a n d  n a b -p a clit a x el  ............................................................................  2 6 
5. 2  
Tr e at m e nt  D ur ati o n  ...............................................................................................  2 6 
5. 3  
C o n c o m it a nt  M e di c ati o ns......................................................................................  2 6 
5. 3. 1  
P er mitt e d  C o n c o mit a nt  M e di c ati o ns  .....................................................................  2 6 
5. 3. 2  
Pr o hi bit e d  C o n c o mit a nt  M e di c ati o ns  a n d  Tr e at m e nts ..........................................  2 7  
5. 4  
C orr el ati v e  St u di es  ................................................................................................  2 7 
5. 4. 1  
T u m or  Tiss u e  S a m pl es ..........................................................................................  2 7  
6.  
D O S E  M O DI FI C A TI O N S  ....................................................................................  2 8 
6. 1  
D os e  M o difi c ati o ns  D u e t o  H e m at ol o gi c  T o xi cit y  ...............................................  2 9 
6. 1. 1  
I n d u cti o n  Tr e at m e nt ( N a b-p a clit a x el  a n d  G e m cit a bi n e) -D a y  1  ............................  2 9 
6. 1. 2  
I n d u cti o n  Tr e at m e nt ( N a b-p a clit a x el  a n d  G e m cit a bi n e) -D a y  8  ............................  3 1 
6. 1. 3  
M ai nt e n a n c e  Tr e at m e nt ( Si n gl e -a g e nt  N a b -p a clit a x el) -D a y  1  .............................  3 1 
6. 2  
D os e  M o difi c ati o ns  D u e t o  N o n- H e m at ol o gi c  T o xi cit y  .......................................  3 2 
7.  
S T U D Y  A S S E S S M E N T S  A N D  E V A L U A TI O N S  ..............................................  3 3 
7. 1  
O v er vi e w  ...............................................................................................................  3 3 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 3  of  6 9  
7. 2  
B as eli n e  St u d y  Ass ess m e nts  .................................................................................  3 3 
7. 3  
St u d y  Tr e at m e nt  Ass ess m e nt s ...............................................................................  3 4 
7. 3. 1  
I n d u cti o n  T h er a p y  wit h  N a b-p a clit a x el/ G e m cit a bi n e  ...........................................  3 4 
7. 3. 2  
M ai nt e n a n c e  T h er a p y  wit h  Si n gl e -A g e nt  N a b -p a clit a x el  .....................................  3 4 
7. 3. 3  
R es p o ns e  Ass ess m e nt  E v er y  3  C y cl es ( ±  7  d a ys)  .................................................  3 5 
7. 4  
E n d  of  St u d y  E v al u ati o n (t o  b e  c o m pl et e d  wit hi n  3 0  d a ys  of tr e at m e nt 
dis c o nti n u ati o n) .....................................................................................................  3 5  
7. 5  
F oll o w- u p ..............................................................................................................  3 6  
7. 5. 1  
F oll o w- u p  pri or t o  dis e as e  pr o gr essi o n  e v er y  6  w e e ks ( ±  7  d a ys): .......................  3 6  
7. 5. 2  
F oll o w- u p  aft er  dis e as e  pr o gr essi o n (s ur vi v al f oll o w  u p) .....................................  3 6  
8.  
D R U G  F O R M U L A TI O N,  A V AI L A BI LI T Y,  A D MI NI S T R A TI O N,  A N D 
T O XI CI T Y I N F O R M A TI O N  ...............................................................................  3 6 
8. 1  
N a b -p a clit a x el  .......................................................................................................  3 6 
8. 1. 1  
L a b eli n g,  P a c k a gi n g,  a n d  S u p pl y ..........................................................................  3 6  
8. 1. 2  
Pr e p ar ati o n  a n d  A d mi nistr ati o n.............................................................................  3 7  
8. 1. 3  
Pr e c a uti o ns  a n d  Ris ks ............................................................................................  3 7  
8. 2  
G e m cit a bi n e ...........................................................................................................  3 7 
8. 2. 1  
L a b eli n g,  P a c k a gi n g,  a n d  S u p pl y ..........................................................................  3 7  
8. 2. 2  
Pr e p ar ati o n  a n d  A d mi nistr ati o n.............................................................................  3 7  
8. 2. 3  
Pr e c a uti o ns  a n d  Ris ks ............................................................................................  3 7  
8. 3  
A c c o u nt a bilit y f or  N a b- p a clit a x el  pr o vi d e d f or t h e  St u d y ....................................  3 7  
9.  
R E S P O N S E  E V A L U A TI O N S  A N D  M E A S U R E M E N T S  ..................................  3 8 
1 0.  
S T A TI S TI C A L  C O N SI D E R A TI O N S  ..................................................................  3 8 
1 0. 1  
St atisti c al  D esi g n  ...................................................................................................  3 8 
1 0. 2  
S a m pl e  Si z e   C o nsi d er ati o ns ..................................................................................  3 8 
1 0. 3  
D at a  A n al ysis  ........................................................................................................  3 8 
1 0. 3. 1  
D e m o gr a p hi cs  a n d  B as eli n e  C h ar a ct eristi cs  .........................................................  3 8 
1 0. 3. 2  
Effi c a c y  A n al ysis  ..................................................................................................  3 9 
1 0. 3. 3  
S af et y  A n al ysis  ......................................................................................................  3 9 
1 0. 3. 4  
C orr el ati v e  St u di es  ................................................................................................  4 0 
1 0. 4  
A n al ysis  Ti m e  P oi nts .............................................................................................  4 0 
1 0. 4. 1  
Fi n al  A n al ysis  ........................................................................................................  4 0 
1 0. 4. 2  
Pl a n n e d I nt eri m  A n al ysis  ......................................................................................  4 0 
1 0. 4. 3  
S af et y  R e vi e w ........................................................................................................  4 0 
1 0. 4. 4  
Effi c a c y  R e vi e w  ....................................................................................................  4 0 
1 1.  
S A F E T Y  R E P O R TI N G  A N D  A N A L Y S E S  .........................................................  4 1 
1 1. 1  
D efi niti o ns  .............................................................................................................  4 1 
1 1. 1. 1  
A d v ers e  E v e nts  ......................................................................................................  4 1 
1 1. 1. 2  
S eri o us  A d v ers e  E v e nt ..........................................................................................  4 1  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 4  of  6 9  
1 1. 1. 3  
A d v ers e  R e a cti o n  ..................................................................................................  4 2 
1 1. 1. 4  
S us p e ct e d  A d v ers e  R e a cti o n  .................................................................................  4 2 
1 1. 1. 5  
R e c or di n g  a n d  R e p orti n g  of  A d v ers e  E v e nts ........................................................  4 2  
1 1. 1. 6  
Ass ess m e nt  of  A d v ers e  E v e nts..............................................................................  4 3  
1 1. 2  
S eri o us  A d v ers e  E v e nt  R e p orti n g  b y I n v esti g at ors ...............................................  4 3  
1 1. 3  
R e c or di n g  of  A d v ers e  E v e nts  a n d  S eri o us  A d v ers e  E v e nts ..................................  4 4  
1 1. 3. 1  
Di a g n osis  v ers us  Si g ns  a n d  S y m pt o ms .................................................................  4 4  
1 1. 3. 2  
P ersist e nt  or  R e c urr e nt  A d v ers e  E v e nts  ................................................................  4 4 
1 1. 3. 3  
A b n or m al  L a b or at or y  V al u es ................................................................................  4 4  
1 1. 3. 4  
D e at hs  ....................................................................................................................  4 5 
1 1. 3. 5  
H os pit ali z ati o n,  Pr ol o n g e d  H os pit ali z ati o n,  or  S ur g er y ........................................  4 5  
1 1. 3. 6  
Pr e -E xisti n g  M e di c al  C o n diti o ns  ..........................................................................  4 5 
1 1. 3. 7  
N e w  C a n c ers ..........................................................................................................  4 6 
1 1. 3. 8  
Pr e g n a n c y,  A b orti o n,  Birt h  D ef e cts / C o n g e nit al  A n o m ali es .................................  4 6 
1 1. 3. 9  
O v er d os e  of  N a b -p a clit a x el  of  G e m cit a bi n e  .........................................................  4 7 
1 1. 4  
S p o ns or  S eri o us  A d v ers e  E v e nt  R e p orti n g  R e q uir e m e nts  ....................................  4 7 
1 1. 4. 1  
S p o ns or  Ass ess m e nt  of  U n e x p e ct e d......................................................................  4 8  
1 1. 4. 2  
S p o ns or  R e p orti n g f or  Cli ni c al  St u di es  U n d er  a n I n v esti g ati o n al  N e w  Dr u g 
A p pli c ati o n  ............................................................................................................  4 8 
1 2.  
E T HI C A L,  FI N A N CI A L,  A N D  R E G U L A T O R Y  C O N SI D E R A TI O N S  ............  4 8 
1 2. 1  
I nstit uti o n al  R e vi e w  B o ar d  A p pr o v al....................................................................  4 9 
1 2. 2  
R e g ul at or y  A p pr o v al  .............................................................................................  4 9 
1 2. 3  
I nf or m e d  C o ns e nt ..................................................................................................  4 9 
1 2. 3. 1  
C o nfi d e nti a lit y .......................................................................................................  5 0 
1 2. 4  
Fi n a n ci al I nf or m ati o n  ............................................................................................  5 1 
1 3.  
R E S E A R C H  R E T E N TI O N  A N D  D O C U M E N T A TI O N  O F  T H E  S T U D Y  ........  5 1 
1 3. 1  
A m e n d m e nts t o t h e  Pr ot o c ol .................................................................................  5 1  
1 3. 2  
D o c u m e nt ati o n  R e q uir e d t o I niti at e t h e  St u d y  ......................................................  5 1 
1 3. 3  
St u d y  D o c u m e nt ati o n  a n d  St or a g e ........................................................................  5 2  
1 3. 4  
D at a  C oll e cti o n  ......................................................................................................  5 4 
1 3. 5  
St u d y  M o nit ori n g,  A u diti n g,  a n d I ns p e cti n g .........................................................  5 4  
1 3. 6  
Q u alit y  Ass ur a n c e  a n d  Q u alit y  C o ntr ol ................................................................  5 4  
1 3. 7  
Dis cl os ur e  a n d  P u bli c ati o n  P oli c y .........................................................................  5 5  
1 4.  
R E F E R E N C E S  ......................................................................................................  5 6 
1 5.  
A P P E N DI C E S  .......................................................................................................  6 0 
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 5  of  6 9  
LI S T  O F  T A B L E S  
T a bl e  1  
D os e  L e v el  M o difi c ati o ns ........................................................................  2 8  
T a bl e  2  
D os e  R e d u cti o n s  of  N a b -p a clit a x el  a n d  G e m cit a bi n e  B as e d  o n  D a y  1 
Bl o o d  C o u nts  D uri n g I n d u cti o n  T h er a p y  ................................................ 3 0  
T a bl e  3  
D os e  R e d u cti o ns  of  N a b- p a clit a x el  a n d  G e m cit a bi n e  B as e d  o n  D a y  8 
Bl o o d  C o u nts  D uri n g I n d u cti o n  T h er a p y ................................................  3 1  
T a bl e  4  
D os e  R e d u cti o ns  of  M ai nt e n a n c e  N a b -p a clit a x el  b as e d  o n  D a y  1 
Bl o o d  C o u nts  ........................................................................................... 3 2  
T a bl e  5  
D os e  R e d u cti o ns f or  Gr a d e  3  or  4  N o n- H e m at ol o gi c  T o xi citi es  ............. 3 3  
LI S T  O F  FI G U R E S  
Fi g ur e  1  
St u d y  S c h e m a ........................................................................................... 2 5  
 
LI S T  O F  A P P E N DI C E S  
A p p e n di x  A:  
E C O G  P erf or m a n c e  St at us  Crit eri a  .........................................................  6 0 
A p p e n di x  B:  
N e w  Y or k  H e art  Ass o ci ati o n ( N Y H A)  Cl assifi c ati o n  of  C ar di a c 
Dis e as e  .....................................................................................................  6 1 
A p p e n di x  C:  
G ui d eli n es f or  F e m al e  P ati e nts  of  C hil d b e ari n g  P ot e nti al  a n d  F ertil e 
M al e  P ati e nts  ............................................................................................  6 2 
A p p e n di x  D:  
S c h e d ul e  of  Ass ess m e nts  .........................................................................  6 4 
A p p e n di x  E:  
R es p o ns e  E v al u ati o n  Crit eri a i n  S oli d  T u m ors ( R E CI S T)  V ersi o n  1. 1...  6 6  
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 6  of  6 9  
1.   
I N T R O D U C TI O N 
1. 1   
B a c k g r o u n d 
A c c or di n g t o  t h e  A m eri c a n  C a n c er  S o ci et y r e p ort i n  y e ar  2 0 1 5,  ur ot h eli al  c ar ci n o m a ( U C) is t h e 
f o urt h  m ost  c o m m o n  c a n c er ( ~ 7 4, 0 0 0  n e w  c as es  a  y e ar),  a n d is t h e  ei g ht h  m ost  c o m m o n  c a us e  of 
d e at h i n  m e n i n t h e  U S A ( Si e g el  et  al.  2 0 1 5 ).  A p pr o xi m at el y  2 5 %  of  n e w  c as es  h a v e  m us cl e -
i n v asi v e  dis e as e  wit h  or  wit h o ut  m et ast as es.  A p pr o xi m at el y  5 0 %  of  p ati e nts  wit h l o c ali z e d 
m us cl e i n v asi v e  U C  will  d e v el o p  m et ast ati c  dis e as e  d es pit e  o pti m al s ur gi c al  a n d  p eri o p er ati v e 
c h e m ot h er a p y  (St ei n  et  al.  2 0 0 6 , Gr oss m a n  et  al.  2 0 0 3 , I nt er n ati o n al  C oll a b or ati o n  of  Tri alist 
2 0 1 1 , A d v a n c e d  Bl a d d er  C a n c er  C oll a b or at i o n  2 0 0 5, S h ari at  et  al.  2 0 0 6 a , S h ari at  et  al.  2 0 0 6 b , 
I nt er n ati o n al  Bl a d d er  C a n c er  N o m o gr a m  C o ns orti u m  et  al.  2 0 0 6).   L o c all y  a d v a n c e d  or 
m et ast ati c  U C is i niti all y  r es po nsi v e t o first -li n e t h er a p y (o v er all r es p o ns e r at e  [O R R ],  5 0- 7 0 %; 
c o m pl et e r es p o ns e [ C R] r at e,  1 0- 2 0 %).  I n  a d diti o n,  a  mi n orit y  of  p ati e nts ( a p pr o xi m at el y  5-
1 5 %)  h a v e l o n g- t er m  dis e as e-fr e e s ur vi v al f oll o wi n g tr e at m e nt  wit h  c o n v e nti o n al  cis pl ati n-b as e d 
r e gi m e ns (L o g ot h etis   et  al.  1 9 9 0, v o n  d er  M a as e  et  al.  2 0 0 0 , S a x m a n   et  al.  1 9 9 7, L o e hr er  et  al. 
1 9 9 2 , St er n b er g   et  al.  2 0 0 6).  
Alt h o u g h s o m e  p ati e nts  wit h  a d v a n c e d  U C  d eri v e s u bst a nti al  b e n efit fr o m tr e at m e nt, t h e  m e di a n 
pr o gr essi o n-fr e e s ur vi v al ( P F S)  a n d  o v er all s ur vi v al ( O S) f or t h e  e ntir e  gr o u p  ar e  o nl y  8  a n d  1 5 
m o nt hs, r es p e cti v el y ( L o g ot h etis   et  al.  1 9 9 0, v o n  d er  M a as e  et  al.  2 0 0 0 , S a x m a n   et  al.  1 9 9 7, 
L o e hr er   et  al.  1 9 9 2, St er n b er g   et  al.  2 0 0 6, G als k y   et  al.  2 0 1 2).  T w o  m aj or  pr o g n osti c f a ct ors, 
K ar n ofs k y  p erf or m a n c e st at us ( K P S)  < 8 0  a n d  vis c er al  m et ast asis,  c a n  b e  us e d t o  d efi n e  p ati e nt 
gr o u ps  wit h  m ar k e dl y  diff er e nt s ur vi v al ( B aj ori n   et  al.  1 9 9 9).   M e di a n  O S f or  p ati e nts  wit h  z er o, 
o n e,  or t w o ris k f a ct ors  ar e  3 3,  1 3. 4,  a n d  9. 3  m o nt hs, r es p e cti v el y.   P ati e nts  wit h  c o m pl et e 
r e missi o n  a n d l o n g-t er m s ur vi v al f oll o wi n g  cis pl ati n-b as e d t h er a p y  ar e  al m ost  al w a ys i n t h e  m ost 
f a v or a bl e  gr o u p (i. e.  g o o d  K P S,  n o  vis c er al  m et ast as es).   C o n v ers el y,  p ati e nts  wit h  vis cer al 
m et ast as es r ar el y  h a v e  c o m pl et e r es p o ns es  or l o n g -t er m s ur vi v al  aft er st a n d ar d cis pl ati n -b as e d 
c h e m ot h er a p y,  a n d  h a v e  b e e n  d efi n e d  as  cis pl ati n -i n c ur a bl e  a n d i n cl u d e d i n tri als  a c cr ui n g 
cis pl ati n -i n eli gi bl e  p ati e nts (B al ar  et  al.  2 0 1 3 ). 
At  pr es e nt, t h e  c o m bi n ati o n  of  g e m cit a bi n e  a n d  cis pl ati n ( G C) is t h e  pr ef err e d first- li n e r e gi m e n 
f or t h e tr e at m e nt  of p ati e nts  wit h  a d v a n c e d  ur ot h eli al  c a n c er.  I n  a  P h as e  III st u d y,  G C  h a d 
si mil ar  effi c a c y  o ut c o m es  b ut  b ett er t ol er a bilit y  c o m p ar e d t o  a  c o m bi n ati o n  of  m et h otr e x at e, 
vi n bl asti n e,  d o x or u bi ci n,  cis pl ati n  (M V A C ), t h e  pr e vi o us st a n d ar d of  c ar e ( v o n  d er  M a as e  et  al. 
2 0 0 0 , v o n  d er  M a as e  et  al.  2 0 0 5 ). 
O n e  of t h e  m aj or  pr o bl e ms i n  m a n a g i n g  p ati e nts  with  a d v a n c e d  U C is t h at  m a n y  of t h es e  p ati e nts 
ar e  u n a bl e t o t ol er at e  c o n v e nti o n al  cis pl ati n -b as e d  c h e m ot h er a p y.   P ati e nts  wit h  a d v a n c e d  U C 
h a v e  a  m e di a n  a g e  of  6 5 -7 0  y e ars,  a n d fr e q u e ntl y  h a v e  ass o ci at e d  c o m or bi diti es  a n d  p o or 
p erf or m a n c e st at us ( P S ).   A d diti o n,  a p pr o xi m at el y  5 0 %  of  p ati e nts  wit h  a d v a n c e d  U C  h a v e  a g e-
d e p e n d e nt  di mi nis h e d r e n al f u n cti o n ( G als k y   et  al.  2 0 1 1 a, D as h  et  al.  2 0 0 6 , S o n p a v d e  et  al. 
2 0 1 4 ).  Cli ni c al f e at ur es  u ni v ers all y  ass o ci at e d  wit h  p o or t ol er a n c e  of  cis pl ati n i n cl u d e r e n al 
d ysf u n cti o n ( esti m at e d  cr e ati ni n e  cl e ar a n c e [ Cr  Cl]  < 6 0  ml/ mi n)  a n d  p o or  p erf or m a n c e st at us 
( E ast er n  C o o p er ati v e  O n c ol o g y  Gr o u p [E C O G ]  P S ≥ 2).  I n  a d diti o n, fr ailt y  ass o ci at e d  wit h 
a d v a n c e d  a g e  a n d s e v er al  ot h er  c o m or bi diti es ( e. g.  Gr a d e   ≥  2  h e ari n g l oss, Gr a d e   ≥  2 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 7  of  6 9  
n e ur o p at h y,  N e w  Y or k  H e art  Ass o ci ati o n  Cl ass  [ N Y H A] III  h e art f ail ur e)  m a y  als o r e n d er 
p ati e nts  cis pl ati n -i n eli gi bl e (G als k y   et  al.  2 0 1 1 a, G als k y   et  al.  2 0 1 1 b). 
T h e  diffi c ulti es i n v ol v e d i n tr e ati n g  p ati e nts  wit h  a d v a n c e d  bl a d d er  c a n c er  ar e r efl e ct e d i n t h e 
pr a cti c e  p att er ns  d o c u m e nt e d i n r e c e nt st u di es.  I n  a r etr os p e cti v e  a n a l ysis,  o nl y  1 0 7  of  2 9 9 
p ati e nts ( 3 6 %)  wit h st a g e I V  U C  w h o  w er e  m a n a g e d i n  a  c o m m u nit y- b as e d  c a n c er  c e nt er s yst e m 
r e c ei v e d  cis pl ati n-b as e d  c h e m ot h er a p y; t h e r e m ai n d er r e c ei v e d  c ar b o pl ati n -b as e d tr e at m e nt 
( 2 7 %),  n o n pl ati n u m-b as e d  c h e m ot h er a p y ( 8 . 4 %),  or  n o c h e m ot h er a p y ( 2 4 %) ( D as h  et  al.  2 0 0 6 ).  
I n  a n ot h er r etr os p e cti v e st u d y  of  1 0 3 1  p ati e nts  wit h  a d v a n c e d  U C  a n d  a g e d  ≥ 6 6  y e ars,  4 8 % 
r e c ei v e d  n o  c h e m ot h er a p y;  o nl y  2 0 % r ec ei v e d  cis pl ati n -b as e d t h er a p y ( S o n p a v d e  et  al.  2 0 1 2 ).  
Alt h o u g h t h e r e as o ns f or  n o n- a d mi nistr ati o n  of  cis pl ati n  w er e  n ot  a v ail a bl e i n  eit h er  of t h es e 
st u di es,  v ari o us  c o m bi n ati o ns  of r e n al  d ysf u n cti o n,  p o or  p erf or m a n c e st at us,  el d erl y  a g e  a n d 
c o m or bi diti es  ar e li k el y .  
1. 2   
T r e at m e nt f o r  a d v a n c e d  u r ot h eli al  c a r ci n o m a i n  cis pl ati n -i n eli gi bl e  p ati e nts 
C ar b o pl ati n is  oft e n s u bstit ut e d f or  cis pl ati n i n  cis pl ati n -i n eli gi bl e  p ati e nts,  b ut is  ass o ci at e d  wit h 
i nf eri or r es p o ns e r ates,  es p e ci all y  C R  (G als k y   et  al.  2 0 1 2).  I n  a  m et a- a n al ysis  of r a n d o mi z e d 
P h as e  II tri als,  cis pl ati n-b as e d  c h e m ot h er a p y  w as  ass o ci at e d  wit h  a si g nifi c a ntl y  hi g h er 
li k eli h o o d  of  a c hi e vi n g  a  C R (r el ati v e ris k [ R R]  =  3. 5 4  a n d  9 5 %  c o nfi d e n c e i nt er v al [ CI]  1. 4 8-
8. 4 9;  P  =  0. 0 0 5)  a n d  O R R ( R R  =  1. 3 4;  9 5 %  CI  1. 0 4- 1. 7 1;  P  =  0. 0 2 ( G als k y   et  al.  2 0 1 2).   A 
P h as e  III tri al  c o m p ari n g g e m cit a bi n e - c ar b o pl ati n  wit h  M C A VI ( m et h otr e x at e,  c ar b o pl ati n, 
vi n bl asti n e) i n  p ati e nts  w h o  w er e  cis pl ati n -i n eli gi bl e  d u e t o  p o or p erf or m a n c e st at us ( E C O G  P S 
2)  a n d/ or r e n al  d ysf u n cti o n ( Cr  Cl  > 3 0 t o  < 6 0  ml/ mi n)  d e m o nstr at e d  b ett er t ol er a n c e  of 
g e m cit a bi n e - c ar b o pl ati n,  b ut  wit h  m e di a n s ur vi v als  of  o nl y  8- 9  m o nt hs  wit h  b ot h r e gi m e ns (D e 
S a ntis   et  al.  2 0 1 2).   T his  o ut c o m e is  c o nsi d era bl y  p o or er  t h an  e x p e ct e d f or  g e m cit a bi n e -cis pl ati n .  
It is  n ot  cl e ar  w h et h er t h es e  p o or  o ut c o m es  ar e r el at e d t o  h ost f a ct ors, t u m or  or t h er a p y-r el at e d 
f a ct ors,  or a  c o m bi n ati o n  of  b ot h.   H o w e v er, t h e  c o m p o n e nt(s)  attri b ut a bl e t o s u b o pti m al t h er a p y 
m a y  b e  m o difi e d  b y  i m pr o vi n g s yst e mi c  c h e m ot h er a p y. 
1. 3   
N a b - p a clit a x el 
N a b -p a clit a x el ( A br a x a n e ® [ A BI - 0 0 7]) is  an i nj e ct a bl e   pr o pri et ar y s ol v e nt-fr e e,  pr ot ei n-
st a bili z e d f or m ul ati o n  of  p a clit a x el  w hi c h  als o  c o nt ai ns  h u m a n  al b u mi n i n  a  n o n cr yst alli n e 
a m or p h o us st at e,  wit h  a  m e a n  p arti cl e si z e  of  a p pr o xi m at el y  1 3 0  n a n o m et ers.   P a clit a x el 
e n h a n c es t h e  p ol y m eri z ati o n  of t u b uli n t o st a bl e  mi cr ot u b ul es  a n d  als o i nt er a cts  dir e ctl y  wit h 
mi cr ot u b ul es, st a bili zi n g t h e m  a g ai nst  d e p ol y m eris ati o n.   T h e  hi g hl y st a bl e t u b uli n  c o m pl e x es 
l e a d t o t h e f or m ati o n  of  dis c or d a nt  a n d  d ysf u n cti o n al  mi cr ot u b ul e  arr a ys,  visi bl e  as  " b u n dl es " 
d uri n g  mit oti c  c ell  di visi o n,  a n d r es ults i n  a p o pt osis  a n d  c ell  d e at h.   N a b- p a clit a x el  h as  a si mil ar 
m o d e  of  a cti o n  a n d  w as  d e v el o p e d t o i m pr o v e t h e t h er a p e uti c i n d e x  a n d r e d u c e t o xi cit y. 
N a b -p a clit a x el  us es  a r e c e pt or - m e di at e d tr a ns p ort  pr o c ess  all o wi n g tr a ns c yt osis  a cr oss t h e 
e n d ot h eli al  c ell  w all, t h er e b y  br e a c hi n g t h e  bl o o d/t u m or i nt erf a c e.   T his  al b u mi n -s p e cifi c 
r e c e ptor  m e di at e d  pr o c ess i n v ol v es  bi n di n g t o  a s p e cif i c r e c e pt or  g p 6 0, a n  e n d ot h eli al  c ell 
m e m br a n e  6 0 -k D a  al b u mi n - bi n di n g  pr ot ei n.   Bi n di n g t o g p 6 0  a cti v at es  c a v e oli n - 1,  w hi c h 
i niti at es t h e  o p e ni n g of  c a v e ol a e  i n t h e  e n d ot h eli al  w all.   T h e  al b u mi n- b o u n d  c h e m ot h er a p e uti c 
c o m pl e x  is t h e n tr a ns p ort e d vi a t h es e   c a v e ol a e t o t h e  u n d erl yi n g t u m or i nt erstiti u m.   A  pr ot ei n 
s p e cifi c all y s e cr et e d  b y t h e t u m or (s e cr et e d  pr ot ei n  a ci di c  a n d ri c h i n  c yst ei n e  or  S P A R C)  bi n ds 
a n d  e ntr a ps t h e  al b u mi n,  all o wi n g r el e as e  of t h e  h y dr o p h o bi c  dr u g t o t h e t u m or  c ell  m e m br a n e.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 8  of  6 9  
N a b - pa clit a x el is t h e first  bi ol o gi c all y i nt er a cti v e  n a n o p arti cl e  w hi c h  e x pl oits t h e  g p - 6 0/ c a v e oli n-
1/ S P A R C  p at h w a y t o  e n h a n c e i ntr a- t u m or al  c o n c e ntr ati o n  of t h e  dr u g,  cr e ati n g t h e  p ot e nti al f or 
i n cr e as e d  effi c a c y  a n d  d e cr e as e d t o xi cit y. 
N a b -p a clit a x el is  c urr e ntl y  a p pr o v e d f or t h e tr e at m e nt  of s e v er al  a d v a n c e d  c a n c ers.  I n  m et ast ati c 
br e ast  c a n c er, first -li n e tr e at m e nt  wit h  w e e kl y  n a b- p a clit a x el r es ult e d i n  pr ol o n g e d  P F S  a n d 
d e cr e as e d t o xi cit y  w h e n  c o m p ar e d t o  st a n d ar d  d os e  d o c et a x el ( Gr a dis h ar  et  al.  2 0 0 9 ).  I n 
a d v a n c e d  p a n cr e ati c  c a n c er, t h e  a d diti o n  of  n a b- p a clit a x el t o  g e m cit a bi n e i m pr o v e d  O S  a n d  w as 
g e n e r all y  w ell t ol er at e d (V o n  H off  et  al.  2 0 1 1 , V o n  H off  et  al.  2 0 1 3 ).  I n t h e first-li n e t h er a p y  of 
a d v a n c e d  n o n- s m all  c ell l u n g  c ar ci n o m a ( N S C L C ),  w e e kl y  n a b-p a clit a x el i n  c o m bi n ati o n  wit h 
c ar b o pl ati n r es ult e d i n  m o d estl y i m pr o v e d  effi c a c y  a n d s u bst a nti all y r e d u c e d t o xi cit y  w h e n 
c o m p ar e d t o st a n d ar d  p a clit a x el - c ar b o pl ati n (S o ci ns ki  et  al.  2 0 1 2 ).  Effi c a c y  a n d t ol er a bilit y 
diff er e n c es  w er e  p arti c ul arl y  e vi d e nt i n t h e s u b gr o u p  of  p ati e nts  ≥ 7 0  y e ars  ol d.  T h er ef or e, t h e 
a u g m e nt ati o n  of  effi c a c y  c o u pl e d  wit h r e d u c e d t o xi cit y  as  pr e di ct e d  b y t h e f or m ul ati o n  a n d 
m e c h a nis m  of  a cti o n  of  n a b- p a clit a x el  h as  b e e n  d e m o nstr at e d  cli ni c all y i n t h e tr e at m e nt  of 
s e v er al  c a n c ers.   
1. 3. 1   
N a b - pa clit a x el i n t h e  T r e at m e nt  of  U r ot h eli al  C a r ci n o m a  
N a b -p a clit a x el  h as  b e e n  e v al u at e d  as  a si n gl e  a g e nt i n  p ati e nts  wit h  a d v a n c e d  U C  w h o 
pr o gr ess e d  wit hi n  1  y e ar  of  pl ati n u m- b as e d t h er a p y ( K o  et  al.  2 0 1 3 ).  I n  a P h as e  II tri al,  4 8 
p ati e nts r e c ei v e d i ntr a v e n o us  (I V) n a b -p a clit a x el ( 2 6 0  m g/ m 2)  e v er y  3  w e e ks.   F ort y s e v e n 
p ati e nts  w er e  e v al u a bl e:  o n e ( 2 %)  h a d  a  c o m pl et e r es p o ns e  a n d  1 2 ( 2 6 %)  h a d  p arti al r es p o ns es , 
r es ulti n g i n  a n  o v er all r es p o ns e  of  2 8 % ( 9 5 %  CI  1 7- 4 4).   T h e  m ost fr e q u e ntl y r e c or d e d  a d v ers e 
e v e nts  ( A Es) of  a n y  gr a d e  w er e f ati g u e ( 7 9 %),   p ai n ( 7 7 %),  al o p e ci a ( 7 1 %),  a n d  n e ur o p at h y 
( 7 7 %).   T h e  m ost fr e q u e ntl y r e c or d e d A Es  of  Gr a d e   3  or  hi g h er  w er e  p ai n ( 2 3 %), f ati g u e ( 2 3 %), 
h y p ert e nsi o n ( 6 %),  n e ur o p at h y ( 6 %),  a n d j oi nt stiff n ess  ( 4 %).   M e di a n  a ct u ari al O S  i n  all 
p ati e nts  w as  1 0 . 8  m o nt hs ( 9 5 %  CI  5. 8 – 1 6. 9)  a n d  m e di a n  P F S  w as  6. 0  m o nt hs ( 9 5 %  CI  3. 9 – 8.5), 
b ot h  c o m p ari n g f a v o r a bl y  wit h  hist ori c al r e gi m e ns (S o n p a v d e  et  al.  2 0 1 3 ).   A n  o n g oi n g 
r a n d o mi z e d P h as e  II tri al is  c o m p ari n g  n a b-p a clit a x el  vs.  p a clit a x el i n t h e s e c o n d -li n e s etti n g.   
1. 4   
G e m cit a bi n e  
G e m cit a bi n e is  a  c yt ot o xi c  a nti c a n c er  dr u g  a n d  c u rr e ntl y  a p pr o v e d f or tr e ati n g  p ati e nts  wit h 
p a n cr e ati c  c a n c er,  br e ast  c a n c er,  o v ari a n  c a n c er,  a n d l u n g  c a n c er.   C yt ot o xi c  a bilit y  of 
g e m cit a bi n e  d e p e n ds  o n  disr u pti o n  of  s p e cifi c  p h as es  of t h e  c ell  c y cl e.   G e m cit a bi n e is  a n 
a nti m et a b olit e t h at  i n hi bits  D N A-s y nt h esis ( S- p h as e)  a n d als o  bl o c ks  pr o gr essi o n fr o m  G 1 t o  S 
p h as e.   G e m cit a bi n e is t y pi c all y   a d mi nist er e d i ntr a v e n o usl y  at  a  d os e  of  1 0 0 0  m g/ m2  o v er  3 0 
mi n ut es  o n  D a ys  1  a n d  8  of  e a c h  2 1- d a y  c y cl e.  
Alt h o u g h  g e m cit a bi n e is  n ot s p e cifi c all y  a p pr o v e d f or  us e i n  m et ast ati c  bl a d d er  c a n c er, t h e 
c o m bi n ati o n  of  g e m cit a bi n e- cis pl ati n is  c urr e ntl y  c o nsi d er e d t h e st a n d ar d first -li n e t h er a p y (v o n 
d er  M a as e   et  al.  2 0 0 0, v o n  d er  M a as e   et  al.  2 0 0 5). I n  a d diti o n, t h e  c o m bi n ati o n  of  g e m cit a bi n e 
wit h  c ar b o pl ati n is  wi d el y  us e d,  a n d is  a n  a cti v e, l ess t o xi c r e gi m e n f or  p ati e nts  w h o  ar e 
pr e di ct e d t o  h a v e  diffi c ulti es t ol er ati n g  a  cis pl ati n - c o nt ai ni n g r e gi m e n.  
1. 5   
R ati o n al e f o r t h e  St u d y  
Gi v e n t h e si n gl e- a g e nt  a cti vit y  of  n a b- p a clit a x el  a n d t h e r ol e  of  g e m cit a bi n e  as  a st a n d ar d 
c o m p o n e nt  of first-li n e t h er a p y, t h e i n v esti g ati o n  of t h e  n a b- p a clit a x el - g e m cit a bi n e  c o m bi n ati o n 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  1 9  of  6 9  
is  a p pr o pri at e.   T h e  a d diti o n  of  p a clit a x el t o  a g e m cit a bi n e - c ar b o pl ati n  c o m bi n ati o n  h as  b e e n 
pr e vi o usl y  e x p l or e d  a n d r es ult e d i n  a  n u m eri c all y i m pr o v e d  O S ( m e di a n  1 5.  8  m o nt hs  vs.  1 2. 7 
m o nt hs  wit h  g e m cit a bi n e- c ar b o pl ati n;  p = 0. 0 7 5) ( B ell m u nt  et  al.  2 0 1 2 ). I n  a d diti o n t o  effi c a c y, 
t h e  c o m bi n ati o n  of  n a b-p a clit a x el -g e m cit a bi n e is li k el y t o  b e  w ell t ol er at e d  b y  p ati e nts  wit h 
a d v a n c e d  bl a d d er  c a n c er  w h o  ar e  p o or  c a n di d at es f or  cis pl ati n - c o nt ai ni n g  c h e m ot h er a p y.   T h e 
c o m bi n ati o n  of  n a b- p a clit a x el -g e m cit a bi n e  h as  b e e n  w ell t ol er at e d  b y  p ati e nts  wit h  a d v a n c e d 
p a n cr e ati c  c a n c er, i n cl u di n g t h os e  w h o  w er e  el d erl y  or  h a d  p o or  p erf or m a n c e st at us ( V o n  H off  et 
al.  2 0 1 3 ). 
A n  a d diti o n al  p ot e nti al  a d v a nt a g e  of  n a b- p a clit a x el is t h e  a bilit y t o  c o nti n u e  a d mi nistr ati o n  as 
m ai nt e n a n c e t h er a p y f oll o wi n g  c o m bi n ati o n t h er a p y.   T his st u d y  ai m s t o  d et er mi n e  w h et h er  a 
c o m bi n ati o n  of  n a b- p a clit a x el  a n d  g e m cit a bi n e  gi v e n f or  6  c y cl es, f oll o w e d  b y  m ai nt e n a n c e  wit h 
n a b -p a clit a x el  al o n e,  m a y  pr o vi d e  a n  e xt e nsi o n  of tr e at m e nt  b e n efit i n  p ati e nts  wit h  cis pl ati n -
i n eli gi bl e l o c all y  a d v a n c e d  or  m et ast ati c U C.  
I n t his P h as e  II st u d y, t h e  c o m bi n ati o n  of  n a b-p a clit a x el -g e m cit a bi n e  will  b e  a d mi nist er e d  as 
first-li n e tr e at m e nt f or  p ati e nts  wit h  a d v a n c e d  bl a d d er  c a n c er  w h o  ar e  p o or  c a n di d at es f or 
cis pl ati n - b as e d  c h e m ot h er a p y (s e e  d efi niti o n  b el o w).  I n  a d diti o n,  p ati e nts  w h o  ar e  c o nsi d er e d 
v er y  u nli k el y t o  h a v e  a  C R   or l o n g-t er m r e missi o n wit h  cis pl ati n  w h o  ar e t er m e d  cis pl ati n -
i n c ur a bl e (i. e.  p ati e nts  wit h  m et ast as es  at  vis c er al sit es, re g ar dl ess  of  p erf or m a n c e st at us ) will  b e 
c a n di d at es f or t his st u d y.  
2.   
S T U D Y  O B J E C TI V E S  
2. 1   
P ri m a r y  O bj e cti v e  
T h e  pri m ar y  o bj e cti v e  of t his  st u d y is t o e v al u at e t h e  effi c a c y  of first -li n e tr e at m e nt  wit h  n a b-
p a clit a x el -g e m cit a bi n e i n  p ati e nts  wit h  a d v a n c e d  ur ot h eli al  c ar ci n o m a  w h o  ar e  eit h er  p o or 
c a n di d at es f or  cis pl ati n - c o nt ai ni n g c h e m ot h er a p y  or  h a v e  vis c er al  m et ast as es  a n d  ar e  cis pl ati n -
i n c ur a bl e.  T h e  pri m ar y  e n d p oi nt is t h e  P F S r at e  at  6  m o nt hs  aft er t h e st art  of tr e at m e nt.  .  
2. 2   
S e c o n d a r y  O bj e cti v es  
T h e s e c o n d ar y  o bj e cti v e s  of t his st u d y ar e  t o  e v al u at e t h e s af et y, O R R , C R  r at e,  an d  O S  wit h  t h e 
n a b -p a clit a x el - g e m cit a bi n e  c o m bi n ati o n.  
2. 3   
E x pl o r at o r y  o bj e cti v es 
T h e  e x pl or at or y  o bj e cti v es  ar e t o  e v al u at e  ar c hi v al t u m or tiss u e  b y i m m u n o hist o c h e mistr y (I H C) 
f or  S P A R C  a n d  g e n e  e x pr essi o n  a n d s e q u e n ci n g  of  a  p a n el  of  g e n es t o  e x a mi n e t h eir  ass o ci ati o n 
wit h  P F S,  O R R  a n d  O S. 
3.   
S T U D Y  P A TI E N T  P O P U L A TI O N  A N D  DI S C O N TI N U A TI O N  
3. 1   
I n cl usi o n  C rit e ri a  
P ati e nts  m ust  m e et t h e f oll o wi n g  crit eri a i n  or d er t o  b e i n cl u d e d i n t h e r es e ar c h  st u d y: 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 0  of  6 9  
1.  
Hist ol o gi c all y  c o nfir m e d  di a g n osis  of  U C t h at is  eit h er  m et ast ati c ( a n y  N +  M 1)  or l o c all y 
a d v a n c e d  a n d  u nr es e ct a bl e ( T 4 b N 0).  A  c o m p o n e nt  of  ur ot h eli al (tr a nsiti o n al  c ell)  
c ar ci n o m a is r e q uir e d.  
2.  
T w o  gr o u ps  of  p ati e nts  ar e  eli gi bl e:   
a.   P o or  c a n di d at es  f or  cis pl ati n-b as e d  c h e m ot h er a p y,  b as e d  o n t h e  pr es e n c e  of  ≥  1 
t h e f oll o wi n g:  
•   Gl o m er ul ar filt r ati o n r at e  of  3 0- 6 0  ml/ mi n ( C o c k cr oft-G a ult  f or m ul a) 
•   E C O G  p erf or m a n c e  st at us s c or e  of 2 ( A p p e n di x  A ) 
•   H e ari n g l oss (tr o u bl e  c o m m u ni c ati n g  wit h  h e ari n g  ai ds  or  h e ari n g l oss  at  ≤  3 
K H z)  
•   Gr a d e  ≥ 3  h e art f ail ur e ( N Y H A  A p p e n di x  B )  
•   A g e  ≥ 8 0  y e ars 
•   Ot h er  c o n c urr e nt ill n ess  w hi c h  m a y  m a k e t h e  p ati e nt  a  p o or  c a n di d at e f or 
r e c ei vi n g  cis pl ati n. 
N ot e:  E nr oll m e nt  of  p ati e nts   wit h  2  or  m or e  of t h es e  crit eri a s h o ul d  o c c ur  o nl y 
aft er  c ar ef ul  c o nsi d er ati o n  b y t h e tr e ati n g  p h y si ci a n r e g ar di n g t h e  p ati e nt’s  a bilit y 
t o t ol er at e  c o m bi n ati o n  c h e m ot h er a p y. 
O R  
b.   P o or  pr o g n osis  a n d  d efi n e d  as  cis pl ati n -i n c ur a bl e d u e t o  t h e  pr es e n c e  of 
m et ast as is t o at  l e ast  o n e vis c er al sit e (t h es e  p ati e nts  ar e  n ot r e q uir e d t o  h a v e  a n y 
of t h e  cis pl ati n -i n eli gi bilit y  crit eri a).  
•   E C O G  p erf or m a n c e  st at us s c or e  of 0,  1,  or  2 ( A p p e n di x  A ). 
3.  
M e as ur a bl e  dis e as e  b y  R es p o ns e  E v al u ati o n  Crit eri a i n  S oli d  T u m or s ( R E CI S T)  v ersi o n 
1. 1 ( A p p e n di x  E ). 
4.  
P ati e nts  wi t h  pr e vi o usl y tr e at e d  br ai n  m et ast as es ar e  eli gi bl e if   
a.   Tr e at m e nt  w as  c o m pl et e d  ≥   4  w e e ks  pri or t o st u d y tr e at m e nt,  
b.   N e ur ol o gi c s y m pt o ms  ar e  mi ni m al   a n d st a bl e  d uri n g t h e  pr e c e di n g  4  w e e ks,  a n d 
c.   M ai nt e n a n c e  d e x a m et h as o n e is  n ot r e q uir e d.  
5.  
A n y  pr e -e xisti n g  p e ri p h er al  n e ur o p at h y  m ust  b e  <  Gr a d e  2. 
6.  
A d e q u at e  h e m at ol o gi c  f u n cti o n at  b as eli n e,  d efi n e d  as: 
-   A bs ol ut e  n e utr o p hil  c o u nt ( A N C)  ≥ 1 5 0 0/ μ L 
-   H e m o gl o bi n  ( H g b) ≥  9  g/ d L  (us e  of  gr o wt h f a ct or  or  r e d  bl o o d  c ell tr a nsf usi o n t o 
a c hi e v e t his l e v el is  all o w e d ) 
-   Pl at el ets   > 1 0 0, 0 0 0/ µ L 
7.  
A d e q u at e li v er f u n cti o n  at  b as eli n e,  d efi n e d  as:  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 1  of  6 9  
-   Bilir u bi n  ≤ 1. 5  m g/ d L 
-   Al a ni n e  a mi n otr a nsf er as e ( A L T)  a n d  as p art at e  a mi n otr a nsf er as e ( A S T)  ≤  2. 5  x 
u p p er li mit  of  n or m al [ U L N] ( u nl ess  b o n e  m arr o w  m et ast as es  ar e  pr es e nt i n t h e 
a bs e n c e  of li v er  m e t ast asis),  ≤ 5  x  U L N if li v er  m et ast as es  ar e  pr es e nt 
8.  
C al c ul at e d  cr e ati ni n e  cl e ar a n c e  ≥ 3 0  m L/ mi n ut e ( C o c k cr oft- G a ult f or m ul a)  
9.  
M al e  p ati e nts  wit h f e m al e  p art n ers  of  c hil d b e ari n g  p ot e nti al  a n d  w o m e n  p ati e nts  of 
c hil d b e ari n g  p ot e nti al  ar e r e q uir e d t o  us e t w o f o r ms  of  a c c e pt a bl e  c o ntr a c e pti o n, 
i n cl u di n g  o n e  b arri er  m et h o d,  d uri n g t h eir  p arti ci p ati o n i n t h e st u d y  a n d f or  3  m o nt hs 
f oll o wi n g l ast  d os e of st u d y  dr u g(s) .   M al e  p ati e nts  m ust  als o r efr ai n fr o m  d o n ati n g 
s p er m  d uri n g t h eir  p arti ci p ati o n i n t h e st u d y ( A p p e n di x  C ). 
1 0.  
W o m e n  of  c hil d b e ari n g  p ot e nti al  ( W o C B P)  m ust  h a v e  a  n e g ati v e s er u m  or  uri n e β -h C G 
pr e g n a n c y  t est  p erf or m e d wit hi n   7 2  h o urs pri or t o st art  of tr e at m e nt  a n d  m ust  us e  t w o 
f or ms  of  a c c e pt a bl e  c o ntr a c e pti o n, i n cl u di n g  o n e  b arri er  m et h o d,  c o ntr a c e pti v e  m et h o d 
d uri n g tr e at m e nt  a n d f or  3  m o nt hs  aft er  c o m pl eti n g tr e at m e nt.  If  a  w o m a n  b e c o mes 
pr e g n a nt  or s us p e cts s h e is  pr e g n a nt  w hil e  p arti ci p ati n g i n t his st u d y, s h e  m ust  a gr e e t o 
i nf or m  h er tr e ati n g  p h ysi ci a n i m m e di at el y. 
1 1.  
A g e  ≥ 1 8  y e ars  
1 2.  
Willi n g n ess  a n d  a bilit y t o  c o m pl y  wit h  st u d y a n d f oll o w - u p  pr o c e d ur es. 
1 3.  
A bilit y t o  u n d erst a n d t h e  n at ur e  of  t his st u d y  a n d  gi v e  writt e n i nf or m e d  c o ns e nt. 
3. 2   
E x cl usi o n  C rit e ri a  
P ati e nts  w h o  m e et  a n y  of t h e f oll o wi n g  crit eri a  will  b e  e x cl u d e d fr o m  st u d y  e ntr y:  
1.   
Pr e vi o us s yst e mi c  c h e m ot h er a p y f or  U C,  wit h t h e  e x c e pti o n  of  p eri o p er ati v e 
( n e o a dj u v a nt  or  a dj u v a nt) tr e at m e nt  or tr e at m e nt  wit h  c o n c urr e nt  c h e m o-r a di ati o n f or 
l o c all y  a d v a n c e d  dis e as e.   All  of t h es e tr e at m e nts  m ust  h a v e  b e e n  c o m pl et e d  >  1  y e ar 
pr e vi o usl y.  
2.   
Pr es e n c e  of s m all - c ell  or s ar c o m at oi d  c o m p o n e nt i n t u m or  hist ol o g y 
3.   
W o m e n  w h o  ar e  p r e g n a nt  or  br e ast-f e e din g  
4.   
M aj or s ur gi c al  pr o c e d ur es  ≤ 2 8  d a ys  of  b e gi n ni n g st u d y  dr u g,  or  mi n or s ur gi c al 
pr o c e d ur es  ≤ 7  d a ys.   N o  w aiti n g r e q uir e d f oll o wi n g  p ort- a- c at h  pl a c e m e nt.  
5.   
A n y  of t h e f oll o wi n g  c ar di a c  dis e as es  c urr e ntl y  or  wit hi n t h e l ast  6  m o nt hs:  
-   Q T c i nt er v al  > 4 8 0  ms ( p e r i nstit uti o n al st a n d ar d) o n s cr e e ni n g  el e ctr o c ar di o gr a m 
(E C G ) 
-   U nst a bl e  a n gi n a  p e ct oris  
-   A c ut e  m y o c ar di al i nf ar cti o n  
-   C o n d u cti o n  a b n or m alit y  n ot  c o ntr oll e d  wit h  p a c e m a k er  or  m e di c ati o n 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 2  of  6 9  
-   Si g nifi c a nt  v e ntri c ul ar  or s u pr a v e ntri c ul ar  arr h yt h mi as ( p ati e nts  wit h  c h r o ni c r at e-
c o ntr oll e d  a tri al fi brill ati o n i n t h e  a bs e n c e  of  ot h er  c ar di a c  a b n or m aliti es  ar e 
eli gi bl e)  
-   V al v ul ar  dis e as e  wit h si g nifi c a nt  c o m pr o mis e i n  c ar di a c f u n cti o n  
6.   
I n a d e q u at el y  c o ntr oll e d  h y p ert e nsi o n (i. e., s yst oli c  bl o o d  pr ess ur e [ S B P]  ≥ 1 8 0  m m H g  or 
di ast oli c  bl o o d  pr ess ur e ( D B P)  ≥ 1 0 0  m m H g) ( p ati e nts  wit h  v al u es  a b o v e t h es e l e v els 
m ust  h a v e t h eir  bl o o d  pr ess ur e ( B P)  c o ntr oll e d  wit h  m e di c ati o n  pri or t o st arti n g 
tr e at m e nt). 
7.   
C urr e ntl y r e c ei vi n g tr e at m e nt  wit h t h er a p e uti c  d os es  of  w arf ari n s o di u m.   H o w e v er,  a 
m a xi m u m  d ail y  d os e  of  1  m g  will  b e  p er mitt e d f or  p ort li n e  p at e n c y.   L o w  m ol e c ul ar 
w ei g ht  h e p ari n is  all o w e d.   
8.   
S eri o us  a cti v e i nf e cti o n  at t h e ti m e  of tr e at m e nt,  or  a n ot h er s eri o us  u n d erl yi n g  m e di c al 
c o n diti o n t h at  w o ul d i m p air t h e  a bilit y  of t h e  p ati e nt t o r e c ei v e  pr ot o c ol tr e at m e nt . 
9.   
K n o w n  di a g n osis  of  h u m a n i m m u n o d efi ci e n c y  vir us,  h e p atitis  B,  or  h e p atitis  C 
(s cr e e ni n g f or t h es e  dis e as es is  n ot r e q uir e d). 
1 0.   
Pr es e n c e  of  ot h er  a cti v e  c a n c ers,  or  hist or y  of tr e at m e nt f or i n v asi v e  c a n c er  ≤ 5  y e ars  
pr e vi o usl y .   P ati e nts  wit h  St a g e I  c a n c er  w h o  h a v e r e c ei v e d  d efi niti v e l o c al tr e at m e nt  a n d 
ar e  c o nsi d er e d  u nli k el y t o r e c ur  ar e  eli gi bl e.   All  p ati e nts  wit h  pr e vi o usl y tr e at e d i n sit u 
c ar ci n o m a (i. e. ,  n o n-i n v asi v e)  ar e  eli gi bl e,  as  ar e  p ati ents  wit h  hist or y  of  n o n- m el a n o m a 
s ki n  c a n c er. 
1 1.   
Ps y c h ol o gi c al, f a mili al, s o ci ol o gi c al,  or  g e o gr a p hi c al  c o n diti o ns t h at  d o  n ot  p er mit 
c o m pli a n c e  wit h t h e  pr ot o c ol. 
3. 3   
Dis c o nti n u ati o n f r o m  St u d y  T r e at m e nt  
P ati e nts  will  b e  dis c o nti n u e d fr o m  st u d y tr e at m e nt f or  a n y  of t h e f oll o wi n g r e as o ns: 
•  
Dis e as e  pr o gr essi o n  
•  
Irr e v ersi bl e  or i nt ol er a bl e t o xi cit y  or  a b n or m al l a b or at or y  v al u es t h o u g ht t o  b e r el at e d t o 
dr u g t o xi cit y 
•  
C o n diti o ns r e q uiri n g t h er a p e uti c i nt er v e nti o n  n ot  p er mitt e d  b y t h e  pr ot o c ol 
•  
I nt er c urr e nt ill n ess (t his  will  b e  at t h e i n v esti g at or’s  dis cr eti o n) 
•  
I n a bilit y  of t h e  p ati e nt t o  c o m pl y  wit h st u d y  r e q uir e m e nts 
•  
P ati e nt r e q u ests t o  dis c o nti n u e tr e at m e nt  
•  
P ati e nt  wit h dr a ws  c o ns e nt fr o m t h e  st u d y  
•  
N o n -c o m pli a n c e/l ost t o f oll o w - u p 
•  
Pr e g n a n c y  
Aft er  dis c o nti n u ati o n fr o m  pr ot o c ol tr e at m e nt,  p ati e nts  m ust  b e f oll o w e d f or  A E s f or  3 0 c al e n d ar 
d a ys  aft er t h eir l ast  d os e  of st u d y  dr u gs .   


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 3  of  6 9  
All  n e w  A Es  o c c urri n g  d uri n g t his  p eri o d  m ust  b e r e p ort e d  a n d f oll o w e d  u ntil r es ol uti o n  u nl ess, 
i n t h e  o pi ni o n  of t h e i n v esti g at or, t h es e  v al u es  ar e  n ot li k el y t o i m pr o v e  b e c a us e  of t h e 
u n d erl yi n g  dis e as e.   I n t his  c as e, t h e i n v esti g at or  m ust r e c or d  his  or  h er r e as o ni n g f or t his 
d e cisi o n i n t h e  p ati e nt ’s  m e di c al r e c or d a n d  as  a  c o m m e nt  i n t h e el e ctr o ni c  C as e  R e p ort  F or m 
( eC R F).  
All  p ati e nts  w h o  h a v e  Gr a d e  3  or  4 l a b or at or y  a b n or m aliti es ( p er  N ati o n al  C a n c er I nstit ut e 
C o m m o n  T er mi n ol o g y  Crit eri a f or  A d v ers e  E v e nts [ N CI  C T C A E]  v   4. 0 3) at t h e ti m e  of 
dis c o nti n u ati o n  m ust  b e f oll o w e d  u ntil t h e l a b or at or y  v al u es  h a v e r et ur n e d t o  Gr a d e  1  or  2, 
u nl ess it is, i n t h e  o pi ni o n  of t h e i n v esti g at or,  n ot li k el y t h at t h es e  v al u es  ar e t o i m pr o v e.  I n t his 
c as e, t h e i n v esti g at or  m ust r e c or d  his  or  h er r e as o ni n g f or  m a ki n g t his  d e cisi o n i n t h e  p ati e nt’s 
m e di c al r e c or d  a n d  as  a  c o m m e nt  i n t h e  eC R F.  
4.   
P A TI E N T  R E GI S T R A T I O N 
T h e  p ati e nt  m ust  willi n gl y  c o ns e nt  aft er  b ei n g i nf or m e d  of t h e  pr o c e d ur es t o  b e f oll o w e d, t h e 
e x p eri m e nt al  n at ur e  of t h e tr e at m e nt,  p ot e nti al  b e n efits, tr e at m e nt  alt er n ati v es, si d e -eff e cts, ris ks , 
a n d  dis c o mf orts.   H u m a n  pr ot e cti o n  c o m mitt e e ( I nstit utio n al  R e vi e w  B o ar d  [I R B/])  a p pr o v al of 
t his  pr ot o c ol  a n d  c o ns e nt f or m is r e q uir e d.   Eli gi bl e  p ati e nts  w h o  wis h t o  p arti ci p at e i n t h e st u d y 
will  b e  e nr oll e d i nt o t h e  st u d y. 
R e gistr ati o n  m ust  o c c ur  pri or t o t h e i niti ati o n  of  pr ot o c ol t h er a p y.   P ati e nts  eli gi bl e t o  p arti ci p at e 
i n t h e st u d y  m a y  b e  e nr oll e d t hr o u g h t h e  S C RI I n n o v ati o ns  C e ntr al  E nr oll m e nt  D es k.   T h e 
e nr oll m e nt  d es k  m a y  b e r e a c h e d  b y  c alli n g ( 8 7 7)  M Y - 1- S C RI.   R e gistr ati o n  m a y  b e  d o n e  vi a f a x 
( 8 6 6)  6 9 9  0 2 5 8  M o n d a y t hr o u g h  Fri d a y,  8: 3 0  a. m. t o  4: 3 0  p. m.,  C e ntr al  St a n d ar d  Ti m e.   P ati e nt 
r e gistr ati o n  will  b e  c o nfir m e d  vi a  e m ail  wit hi n  2 4  h o urs,  or  b y t h e  n e xt  b usi n ess  d a y. 
5.   
S T U D Y  D E SI G N  
T his  o p e n-l a b el  n o n-r a n d o mi z e d  P h as e  II tri al e v al u at e s t h e  effi c a c y  a n d t o xi cit y  of first-li n e 
tr e at m e nt  wit h a  c o m bi n ati o n  of  g e m cit a bi n e  a n d  n a b -p a clit a x el , f oll o w e d  b y m ai nt e n a n c e  n a b -
p a clit a x el  i n p ati e nts  wit h  m et ast ati c  or l o c all y  a d v a n c e d  u nr es e ct a bl e   U C.   T w o  gr o u ps  of 
p ati e nts  will  b e  eli gi bl e f or t his st u d y:    
1)  P ati e nts  w h o  ar e  p o or  c a n di d at es f or tr e at m e nt  wi t h  cis pl ati n-c o nt ai ni n g  c h e m ot h er a p y 
r e gi m e ns,  as  d efi n e d i n  S e cti o n 3. 1   a n d Fi g ur e  1 . 
2)  P at i e nts  wit h  vis c er al  m et ast as es  w h o  ar e i n c ur a bl e  a n d  u nli k el y t o  d eri v e l o n g-t er m  b e n efit 
fr o m tr e at m e nt  wit h  cis pl ati n-b as e d r e gi m e ns.    
All  eli gi bl e  p ati e nts  will r e c ei v e  g e m cit a bi n e ( 1 0 0 0  m g/ m 2) a n d  n a b -p a clit a x el  (1 2 5  m g/ m 2) vi a 
I V i nf usi o n  o n  d a ys  1  a n d  8  of  a  2 1-d a y  c y cl e.   P ati e nts  will  b e s e e n  b y t h e tr e ati n g i n v esti g at or 
e v er y  c y cl e ( 3  w e e ks)  a n d  ass ess e d f or tr e at m e nt r es p o ns e  aft er  e v er y  3  c y cl es ( 9  w e e ks)  of 
tr e at m e nt.  Aft er  u p t o  6  c y cl es  of tr e at m e nt  ar e  d eli v er e d ,  pati e nts  wit h  o bj e cti v e r es p o ns e  ( O R), 
i. e.,  C R  or  P R, or st a bl e  dis e as e  ( S D) will  c o nti n u e tr e at m e nt  wit h  m ai nt e n a n c e si n gl e  a g e nt  n a b -
p a clit a x el ( 2 6 0  m g/ m 2 e v er y  3  w e e ks )  u ntil  pr o gr essi o n  or t o xi citi es  or  p ati e nt  d e cisi o n. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 4  of  6 9  
R es p o ns e t o t h er a p y  will  b e  assi g n e d  usi n g  R E CI S T  v 1. 1.   
T h e  pl a n n e d  e nr oll m e nt f or t his st u d y is  u p t o  5 5  p ati e nts.   
T h e st u d y  s c h e m a is  pr es e nt e d i n Fi g ur e  1 . 
Ar c hi v al  F F P E  t u m or s a m pl es  will  b e  c oll e ct e d fr o m  all  p ati e nts (if  a v ail a bl e) f or  e x pl or at or y 
g e n o mi c  a n d i m m u n o hist o c h e mistr y (I H C)  bi o m ar k er  e v al u ati o ns.  If  ar c hi v al tiss u e is  n ot 
a v ail a bl e  or t h e  p ati e nt is  n ot  all o wi n g t h at t o   b e  us e d f or t his st u d y, r e p e at  bi o ps y is  n ot 
r e q uir e d,  a n d t h e  p ati e nt is  eli gi bl e t o  p arti ci p at e i n t his st u d y.


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 5  of  6 9  
 
Fi g u r e  1  
St u d y  S c h e m a  
A d v a n c e d  U C  p ati e nts ,  cis pl ati n -i n eli gi bl e  b as e d  o n  1  or  m or e 
of t h e f oll o wi n g  crit eri a: 
• 
Gl o m er ul ar  filtr ati o n r at e of  3 0 -6 0  ml/ mi n 
• 
E C O G  p erf or m a n c e s c or e  of  2
• 
H e ari n g  l oss
• 
Gr a d e  3  h e art f ail ur e ( N e w  Y or k  H e art  Ass o ci ati o n) 
• 
A g e  ≥ 8 0  y e ars
• 
Ot h er  c o n c urr e nt ill n ess  w hi c h  m a y  e x cl u d e  p arti ci p ati o n
Or
A d v a n c e d  U C  p ati e nts  wit h  p o or  pr o g n osis  d u e t o t h e 
pr e s e n c e  of  vis c er al  m et ast as e s
I V  N a b-p a clit a x el 
( 1 2 5  m g / m2)
I V  G e m cit a bi n e
( 1 0 0 0  m g / m2)
+
I N D U C TI O N 
P H A S E
D a y  1
D a y  8
D a y  2 1
U p t o
6 
C y cl es
C y cl e  1
P ati e nts  wit h  o bj e cti v e r es p o ns e 
or  st a bl e  dis e as e  a n d  n o 
i nt ol er a bl e t o xi citi es
I V  N a b-p a clit a x el 
( 2 6 0  m g / m2)
M AI N T E N A N C E
P H A S E
D a y  1
D a y  2 1
O n c e  e v er y  3  w e e ks
  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 6  of  6 9  
5. 1   
T r e at m e nt  Pl a n  
5. 1. 1   
G e m cit a bi n e  a n d  n a b - p a clit a x el 
I n d u cti o n  p h as e:  All  p ati e nts i n t his st u d y  will r e c ei v e  n a b -p a clit a x el ( 1 2 5  m g/ m 2) a n d 
g e m cit a bi n e ( 1 0 0 0  m g/ m 2) b y I V  i nf usi o n  o n  D a y  1  a n d  D a y  8  of  e a c h  2 1-d a y  c y cl e .  
R es p o n di n g  or st a bl e  p ati e nts  will  b e tr e at e d  wit h  a  mi ni m u m  of  3  c y cl es  a n d  u p t o  6  c y cl es  
b ef or e st arti n g t h e si n gl e  a g e nt  m ai nt e n a n c e t h er a p y .  D os es  of  g e m cit a bi n e  a n d  n a b -p a clit a x el 
s h o ul d  b e r e c al c ul at e d if t h er e is  a  ≥  1 0 %  c h a n g e i n t h e  p ati e nt’s  b o d y  w ei g ht si n c e t h e  pr e vi o us 
c al c ul ati o n.   
M ai nt e n a n c e  p h as e:   P ati e nts  w h o h a v e  o bj e cti v e r es p o ns e ( C R  or  P R)  or  st a bl e  dis e as e (S D ) 
aft er  c o m pl eti n g  3- 6  c y cl es  of i n d u cti o n t h er a p y  wit h  n a b- p a clit a x el -g e m cit a bi n e  will  c o nti n u e 
tr e at m e nt  wit h si n gl e  a g e nt n a b -p a clit a x el ( 2 6 0  m g/ m 2 I V  e v er y  2 1  d a ys) u ntil  dis e as e 
pr o gr essi o n,  i nt ol er a bl e t o xi cit y  or  p ati e nt  d e cisi o n t o  dis c o nti n u e tr e at m e nt.   P ati e nts  w h o h a v e 
S D  or  r es p o n d t o  n a b-p a clit a x el - g e m cit a bi n e  b ut  c a n n ot  c o m pl et e  6  cy cl es  d u e t o  p o or t ol er a n c e 
m a y s wit c h t o  m ai nt e n a n c e tr e at m e nt  wit h si n gl e -a g e nt  n a b -p a clit a x el  aft er  c o m pl eti n g  a 
mi ni m u m  of  3  c y cl es   of  c o m bi n ati o n t h er a p y. 
5. 2   
T r e at m e nt  D u r ati o n  
P ati e nts  w h o t ol er at e tr e at m e nt  w ell  a n d  d o  n ot  h a v e t u m or  pr o gr essi o n  will r e c ei v e  6  c y cl es  of 
n a b -p a clit a x el/ g e m cit a bi n e , f oll o w e d  b y  n a b- p a clit a x el  al o n e  e v er y  3  w e e ks  u ntil  pr o gr essi o n, 
i nt ol er a bl e t o xi citi es  or  p ati e nt  d e cisi o n.   R a di o gr a p hi c  e v al u ati o n  will  b e p erf or m e d  at  b as eli n e 
a n d r es p o ns e  t o tr e at m e nt  will  b e ass ess e d  e v er y  3  c y cl es ( R E CI S T  v 1. 1),  a n d  e arli er if  cli ni c all y 
w arr a nt e d.    
P ati e nts  w h o  dis c o nti n u e d tr e at m e nt  pri or t o  dis e as e  pr o gr essi o n  will  c o nti n u e t o  h a v e 
r e e v al u ati o ns  p erf or m e d  e v er y  6  w e e ks  u ntil  pr o gr essi o n is  d o c u m e nt e d.  Aft er  dis e as e 
pr o gr essi o n,  al l  p ati e nts  will  b e f oll o w e d f or s ur vi v al; f urt h er  m a n a g e m e nt  will  b e  at t h e 
dis cr eti o n  of t h e tr e ati n g  p h ysi ci a n.   
P ati e nts  will  b e  e v al u at e d f or t o xi cit y  at t h e st art  of  e a c h  c y cl e.    
5. 3   
C o n c o mit a nt  M e di c ati o ns  
P ati e nts  will  b e i nstr u ct e d  n ot t o t a k e  a n y  a d diti o n al  m e di c ati o ns  d uri n g t h e  c o urs e  of t h e st u d y 
wit h o ut  pri or  c o ns ult ati o n  wit h t h e r es e ar c h t e a m.   At  e a c h  visit, t h e  p ati e nt  will  b e  as k e d  a b o ut 
a n y  n e w  m e di c ati o ns  h e/s h e  is t a ki n g  or  h as t a k e n  aft er t h e st art  of t h e st u d y  dr u g. 
5. 3. 1   
P e r mitt e d  C o n c o mit a n t  M e di c ati o ns 
Pr e m e di c ati o n  wit h  a nti -e m eti cs is  all o w e d  a c c or di n g t o st a n d ar d  pr a cti c e  g ui d eli n es.  
M e di c ati o ns  m a y  b e  a d mi nist er e d f or  m ai nt e n a n c e  of  e xisti n g  c o n diti o ns  pri or t o st u d y 
e nr oll m e nt  or f or  n e w  c o n diti o ns t h at  d e v el o p  w hil e  o n st u d y, i n cl u di n g  b ut  n ot li mit e d t o t h e 
f oll o wi n g: 
•   Bis p h os p h o n at e  us e,  as r e c o m m e n d e d  a c c or di n g t o  pr a cti c e  g ui d eli n es 
•   R e c e pt or  a cti v at or  of  n u cl e ar f a ct or  k a p p a - B li g a n d ( R A N K L) i n hi bit or  us e,  as 
r e c o m m e n d e d  a c c or di n g t o  pr a cti c e  g ui d eli n es. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 7  of  6 9  
•   A nti c o a g ul ati o n  wit h  c o u m a di n- d eri v ati v es  will  n ot  b e  p er mitt e d.   H o w e v er,  a  m a xi m u m 
d ail y  d os e  of  1  m g  will  b e  p er mitt e d f or  p ort li n e  p at e n c y.   S h o ul d  a t hr o m b oti c  e v e nt 
o c c ur  w hil e t h e  p ati e nt is r e c ei vi n g tr e at m e nt , t h e  p ati e nt  m a y  c o nti n u e st u d y tr e at m e nt 
b ut l o w  m ol e c ul ar  w ei g h t  h e p ari n ( L M W H)  will  b e t h e  pr ef err e d tr e at m e nt. 
•   T h e  us e  of  gr a n ul o c yt e  c ol o n y- sti m ul ati n g f a ct or ( G-C S F) is  p er mitt e d  d uri n g 
i n v esti g ati o n al t h er a p y  at t h e  dis cr eti o n  of t h e i n v esti g at or, i n  a c c or d a n c e  wit h  A S C O 
g ui d eli n es.   G- C S F  or si mil ar  a g e nts  ar e s tr o n gl y r e c o m m e n d e d f oll o wi n g  Gr a d e  3  or  4 
n e utr o p e ni a  of  d ur ati o n  >  5  d a ys,  or f oll o wi n g  a n y i n ci d e n c e  of f e bril e  n e utr o p e ni a. 
•   T h e  us e  of  er yt hr oi d- sti m ul ati n g f a ct ors (f or  e x a m pl e,  er yt hr o p oi eti n) is  p er mitt e d  at t h e 
dis cr eti o n  of t h e i n v esti g at or  c o nsis t e nt  wit h i nstit uti o n al  g ui d eli n es. 
Ot h er  m e di c ati o ns  c o nsi d er e d  n e c ess ar y f or t h e  p ati e nt’s s af et y  a n d  w ell -b ei n g  m a y  b e  gi v e n  at 
t h e  dis cr eti o n  of t h e i n v esti g at or. 
5. 3. 2   
P r o hi bit e d  C o n c o mit a nt  M e di c ati o ns  a n d  T r e at m e nts  
T h e f oll o wi n g tr e at m e nts  ar e  pr o hi bit e d  w hil e i n t his st u d y:  
•   N o  a nti c a n c er  a g e nts  ot h er t h a n t h e st u d y  m e di c ati o ns s h o ul d  b e  gi v e n t o  p ati e nts.  If s u c h 
a g e nts  ar e r e q uir e d , t h e n t h e  p ati e nt  m ust first  b e  wit h dr a w n fr o m t h e st u d y. 
•   N o r a di ati o n t h er a p y t o  ar e as  of  n e w  m et ast as es  or  w ors e ni n g s y m pt o ms fr o m  k n o w n 
m et ast as es s h o ul d  b e  gi v e n.   T h es e  p ati e nts s h o ul d  b e  c o nsi d er e d t o  h a v e  dis e as e 
pr o gr essi o n  a n d r e m o v e d fr o m st u d y.   P alli ati v e  r a di ati o n t o li mit e d  ar e as  of  b o n e 
m et ast as es is  all o w e d if  l esi o ns w er e  pr es e nt  at  b as eli n e  a n d  p ai n  h as  n ot  w ors e n e d 
s u bst a nti all y.  
•   Tr e at m e nt  wit h  ot h er i n v esti g ati o n al  a g e nts is  n ot  p er mitt e d.   
•   H er b al  pr e p ar ati o ns/ m e di c ati o ns  t h at  ar e  n ot  all o w e d  d uri n g t h e st u d y i n cl u d e:  St. J o h n’s 
w ort,  k a v a,  e p h e dr a ( m a  h u a n g),  gi n g k o  bil o b a,  d e h y dr o e pi a n dr ost er o n e ( D H E A), 
y o hi m b e, s a w  p al m ett o,  a n d  gi ns e n g.   P ati e nts s h o ul d st o p  usi n g t h es e  h er b al  m e di c ati o ns  7 
d a ys  pri or t o first  d os e  of st u d y  dr u g.   Ot h er  h er b al  m e di ci n es s h o ul d  b e  dis c uss e d  wit h  a n d 
a p pr o v e d  b y t h e tr e ati n g  p h ysi ci a n.  
5. 4   
C o r r el ati v e  St u di es  
If  a v ail a bl e, tu m or tiss u e fr o m  ar c hi v al  bi o psi es  will  b e  c oll e ct e d t o  b e  c e ntr all y st u di e d i n t h e 
f ut ur e  wit h s e p ar at e f u n di n g.  P ot e nti al  I H C st u di es p erf or m e d  c e ntr all y  will  i n cl u d e  b ut  ar e  n ot 
li mit e d t o  S P A R C  e x pr essi o n.  G e n e  e x pr essi n g  pr ofili n g  of t u m or tiss u e  usi n g  N a n ostri n g  or 
ot h er si mil ar t e c h n ol o g y  m a y  als o  b e  p erf or m e d.   
5. 4. 1   
T u m o r  Tiss u e  S a m pl es  
Ar c hi v al  F F P E  t u m or s a m pl es ( 1 5  u nst ai n e d sli d es  of  5  µ M t hi c k s e cti o ns  e a c h) will  b e  c oll e ct e d 
d uri n g t h e st u d y .   C orr el ati v e t ests of  pr ot ei n,  R N A  a n d  D N A  e x pr essi o n  o n t h es e s a m pl es  will 
b e  p erf or m e d.   P ati e nts  w h o  d o  n ot  h a v e t u m or s a m pl es  a v ail a bl e fr o m  pr e vi o us  bi o psi es  d o  n ot 
r e q uir e r e p e at  bi o ps y  a n d ar e still  eli gi bl e f or t h e st u d y.    G e n o mi c  D N A is is ol at e d  usi n g 
P h e n ol: C hl or of or m  e xtr a cti o n  b y st a n d ar d  m ol e c ul ar  bi ol o g y t e c h ni q u es.   ds D N A is  q u a ntifi e d 
usi n g t h e  Q u bit  Br o a d  R a n g e  ds D N A  kit (I n vitr o g e n,  C arls b a d,  C A)  a n d  D N A  q u alit y 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 8  of  6 9  
ass ess m e nt is  p erf or m e d  b y  g el  el e ctr o p h or esis.  R N A is  h ar v est e d  usi n g t h e  Qi a g e n  R N A e as y  kit 
a n d  q u alit y  of  R N A is  c o nfir m e d  vi a t h e  2 6 0/ 2 8 0 r ati o  usi n g  n a n o dr o p.   F ut ur e  pr ot ei n  ass a ys 
i n cl u d e i m m u n o hist o c h e mistr y (I H C) f or  S P A R C  e x pr essi o n.  D N A  a n d  R N A  e v al u ati o ns 
i n cl u d e  N e xt  G e n er ati o n  S e q u e n ci n g  a n d  N a n ostri n g  g e n e  e x pr essi o n t o  e v al u at e  g e n es i n t h e 
P a n C a n  p a n el  of  7 7 0  ess e nti al  c a n c er  p at h w a y  a n d  dri v er  g e n es  .  T h e I H C f or  S P A R C  a n d  g e n e 
e x pr essi o n  a n d s e q u e n ci n g  d at a  will  b e  e x a mi n e d f or t h eir  ass o ci ati o n  wit h  P F S,  O R R  a n d  O S. 
6.   
D O S E  M O DI FI C A TI O N S  
If t o xi cit y  o c c urs, t h e t o xi cit y  will  b e  gr a d e d utili zi n g t h e  N CI  C T C A E  v   4. 0 3 
(htt p:// e vs. n ci. ni h. g o v/ft p 1/ C T C A E/ C T C A E ),  a n d  a p pr o pri at e s u p p orti v e  c ar e tr e at m e nt  will  b e 
a d mi nist er e d t o  d e cr e as e t h e si g ns  a n d s y m pt o ms t h er e of.   D os e  a dj ust m e nts  will  b e  b as e d  o n t h e 
or g a n s yst e m  e x hi biti n g t h e  gr e at est  d e gr e e  of t o xi cit y.  
D os es  of  n a b -p a clit a x el  a n d  g e m cit a bi n e  will  b e  m o difi e d  b as e d  o n  h e m at ol o gi c  a n d  n o n-
h e m at ol o gi c t o xi cit y.   A  m a xi m u m  of  2  d os e r e d u cti o ns  of  n a b- p a clit a x el  a n d  g e m cit a bi n e  ar e 
all o w e d  d uri n g  b ot h t h e i n d u cti o n  a n d  m ai nt e n a n c e tr e at m e nt ( T a bl e  1 ). If t o xi cit y r e c urs  aft er  2 
d os e r e d u cti o ns, t h e r es p o nsi bl e  dr u g  or  dr u gs s h o ul d  b e  dis c o nti n u e d.  If  o nl y  1  dr u g is 
dis c o nti n u e d, t h e  p ati e nt  m a y  c o nti n u e  o n t h e  ot h er  dr u g.   D os e r e d u cti o ns  of  g e m cit a bi n e  a n d 
n a b -p a clit a x el  ar e  p er m a n e nt f or t h e r e m ai n d er  of st u d y tr e at m e nt.   
Tr e at m e nt  d uri n g t h e i n d u cti o n  a n d t h e  m ai nt e n a n c e  p h as es  m a y  b e  d el a y e d  u p t o  3  w e e ks t o 
all o w r e c o v er y fr o m tr e at m e nt -r el at e d t o xi cit y.   P ati e nts s h o ul d  b e r e-e v al u at e d  w e e kl y  w hil e 
tr e at m e nt is  b ei n g  h el d.  If t o xi cit y  h as  n ot i m pr o v e d t o Gr a d e   ≤ 1  aft er  3  w e e ks, t h e r es p o nsi bl e 
dr u g(s) s h o ul d  b e  dis c o nti n u e d.   
T a bl e  1  
D os e  L e v el  M o difi c ati o ns  
I n d u cti o n  p h as e: 
D os e  L e v el  
N a b - p a clit a x el 
G e m cit a bi n e  
St arti n g  D os e   
1 2 5  m g/ m 2 
1 0 0 0  m g/ m 2 
D os e  L e v el  - 1 
1 0 0 m g/ m 2 
8 0 0  m g/ m 2 
D os e  L e v el  - 2 
8 0  m g/ m 2 
6 0 0  m g/ m 2 
 
M ai nt e n a n c e  p h as e:  
D os e  L e v el  
N a b - p a clit a x el 
 
St arti n g  D os e   
2 6 0  m g/ m 2 
 
D os e  L e v el  - 1 
2 2 0  m g/ m 2 
 
D os e  L e v el  - 2 
1 8 0  m g/ m 2 
 
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  2 9  of  6 9  
6. 1   
D os e  M o difi c ati o ns  D u e t o  H e m at ol o gi c  T o xi cit y 
H e m at ol o gi c t o xi cit y is  a  c o m m o n  a n d  e x p e ct e d t o xi cit y  c a us e d  b y  n a b -p a clit a x el  a n d 
g e m cit a bi n e.   M a n a g e m e nt  a n d  d os e  m o difi c ati o ns f or  n e utr o p e ni a  a n d t hr o m b o c yt o p e ni a  ar e 
o utli n e d i n  T a bl e  2 , T a bl e  3 ,  a n d T a bl e  4 .  G e n er all y,  d os e r e d u cti o ns ( wit h o ut  pr o p h yl a cti c  G-
C S F)  ar e  c o nsi d er e d  b as e d  o n  h e m at ol o gi c t o xi citi es,  b ut  pr o p h yl a cti c  G- C S F  m a y  b e  c o nsi d er e d 
fr o m  c y cl e  1 d a y  8 - 9 p er  A S C O  g ui d eli n es  or l at er if t h e  p ati e nt is  b e n efiti n g fr o m t h er a p y  a n d it 
is  d e e m e d i n t h e  b est i nt er est  of t h e  p ati e nt t o  m ai nt ai n  d os e. 
6. 1. 1   
I n d u cti o n  T r e at m e nt ( N a b - p a clit a x el  a n d  G e m cit a bi n e)- D a y  1 
N a b -p a clit a x el   a n d  g e m cit a bi n e  d osi n g s h o ul d  n ot  b e  a d mi nist er e d  at t h e st art  of  e a c h  c y cl e  u ntil 
t h e  A N C r et ur ns t o  ≥ 1. 5  x  1 09  c ells/ L  a n d t h e  pl at el et  c o u nt r et ur ns t o  ≥ 1 0 0  x  1 09 c ells/ L .  
T a bl e   2 s u m m ari z es t h e r e q uir e d i nt er v e nti o ns  a n d  d os e r e d u cti o ns  b as e d  o n  bl o o d  c o u nts 
d et er mi n e d  o n  D a y  1  of  e a c h tr e at m e nt  c y cl e.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 0  of  6 9  
  
T a bl e  2  
D os e  R e d u cti o ns  of  N a b- p a clit a x el  a n d  G e m cit a bi n e  B as e d  o n  D a y  1  Bl o o d 
C o u nts  D u ri n g I n d u cti o n  T h e r a p y  
E v e nt  
M a n a g e m e nt 
D os e  M o difi c ati o n  
N e ut r o p e ni a ( A N C)  
 
N a b - p a clit a x el 
G e m cit a bi n e  
A N C  > 1 5 0 0/ µ L 
A d mi nist er  d os e  
N o  d os e r e d u cti o n   
N o  d os e r e d u cti o n  
A N C  5 0 0 - 1 5 0 0/µ L 
D el a y  d os e  1  w e e k  or 
u ntil  A N C  > 1 5 0 0/ µ L 
 
N o  d os e r e d u cti o n   
1  d os e l e v el r e d u cti o n  
A N C  < 5 0 0/ µ L  
or 
D a y  8  o mitt e d  d uri n g 
pr e vi o us  c y cl e  d u e t o 
n e utr o p e ni a 
or 
F e bril e  n e utr o p e ni a 
d uri n g  p r e vi o us  c y cl e 
D el a y  d os e  1  w e e k  or 
u ntil  A N C  >  1 5 0 0/ µ L 
1  d os e l e v el r e d u cti o n   
1  d os e l e v el r e d u cti o n  
T h r o m b o c yt o p e ni a 
 
 
 
Pl at el ets  > 1 0 0, 0 0 0/ µ L 
A d mi nist er  d os e  
N o  d os e r e d u cti o n   
N o  d os e r e d u cti o n  
Pl at el ets  7 5, 0 0 0 -
1 0 0, 0 0 0/ µ L 
D el a y  d os e  1  w e e k  or 
u ntil  pl a t el et  c o u nt  > 
1 0 0, 0 0 0/ µ L  
N o  d os e r e d u cti o n   
1  d os e l e v el r e d u cti o n  
Pl at el ets  
< 7 5, 0 0 0/ µ L 
or 
Pl at e l et tr a nsf usi o n 
r e q uir e d  d uri n g 
pr e vi o us  c y cl e  
or 
D a y  8   d os e  o mitt e d 
d uri n g  pr e vi o us  c y cl e 
d u e t o 
t hr o m b o c yt o p e ni a 
or 
Bl e e di n g  ass o ci at e d 
wit h t hr o m b o c yt o p e ni a 
d uri n g  pr e vi o us  c y cl e  
D el a y  d os e  1  w e e k  or 
u ntil  pl at el et  c o u nt  > 
1 0 0, 0 0 0/ µ L 
1  d os e l e v el r e d u cti o n   
1  d os e l e v el r e d u cti o n  
 
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 1  of  6 9  
6. 1. 2   
I n d u cti o n  T r e at m e nt ( N a b - p a clit a x el  a n d  G e m cit a bi n e)- D a y  8 
D a y  8  d osi n g  of  n a b- p a clit a x el  a n d  g e m cit a bi n e  will  b e  a d mi nist er e d if  t h e A N C  ≥ 1 0 0 0/ µ L  a n d 
pl at el ets  ≥ 7 5 , 0 0 0/µ L.  If  eit h er  c o u nt is l o w er t h a n t h es e l e v els, t h e  D a y  8  d os e  will  b e  o mitt e d.  
T ot al  c y cl e l e n gt h  will r e m ai n  at  2 1  d a ys.   T a bl e  3  s u m m ari z es t h e r e q uir e d i nt er v e nti o ns  a n d 
s u bs e q u e nt  d os e r e d u cti o ns  b as e d  o n  bl o o d  c o u nts  d et er mi n e d  o n  D a y  8  of  e a c h tr e at m e nt  c y cl e.  
T a bl e  3     
D os e  R e d u cti o ns  of  N a b- p a clit a x e l  a n d  G e m cit a bi n e  B as e d  o n  D a y  8  Bl o o d 
C o u nts  D u ri n g I n d u cti o n  T h e r a p y  
E v e nt  
M a n a g e m e nt 
D os e  M o difi c ati o n  
 
 
N a b - p a clit a x el 
G e m cit a bi n e  
A N C  ≥ 1 0 0 0/ µ L  
a n d  pl at el ets 
≥ 7 5, 0 0 0/ µ L  
A d mi nist er  d os e 
N o  d os e r e d u cti o n   
N o  d os e r e d u cti o n  
A N C  < 1 0 0 0/ µ L  
O R  Pl at el ets 
< 7 5, 0 0 0/ µ L 
 
 
 
 
First  e pis o d e   
O mit  D a y  8  d os e  
 
N o  d os e r e d u cti o n 
b e gi n ni n g  D a y  1  of  n e xt 
c y cl e  
R e d u c e  b y  1  d os e l e v el   
b e gi n ni n g  D a y  1  of  n e xt 
c y cl e  
S e c o n d  e pis o d e   
O mit  D a y  8  d os e  
 
R e d u c e  b y  1  d os e l e v el 
b e gi n ni n g  D a y  1  of  n e xt 
c y cl e  
R e d u c e  b y  1  d os e l e v el 
b e gi n ni n g  D a y  1  of  n e xt 
c y cl e  
Pl at el ets 
< 7 5, 0 0 0/ µ L  A N D   
A N C  < 1, 0 0 0/ µ L  
O mit  D a y  8  d os e  
 
R e d u c e  b y  1  d os e l e v el 
b e gi n ni n g  D a y  1  of  n e xt 
c y cl e  
R e d u c e  b y  1  d os e l e v el 
b e gi n ni n g  D a y  1  of  n e xt 
c y cl e  
6. 1. 3   
M ai nt e n a n c e  T r e at m e nt ( Si n gl e - a g e nt  N a b- p a clit a x el)- D a y  1 
If  d os e r e d u cti o ns  of  n a b- p a clit a x el  w er e r e q uir e d  d uri n g i n d u cti o n t h er a p y, t h e  m at c hi n g  n a b-
p a clit a x el  d os e  r e d u cti o n (i. e. s a m e l e v el  of  d os e r e d u cti o n) s h o ul d  b e  us e d t o s h o ul d  b e  us e d t o 
st art  m ai nt e n a n c e t h er a p y ( S e e  T a bl e  1 ). 
T a bl e  4  s u m m ari z es t h e r e q uir e d i nt er v e nti o ns  a n d  d os e r e d u cti o ns  b as e d  o n  bl o o d  c o u nts 
d et er mi n e d  o n  D a y  1  of  e a c h  m ai nt e n a n c e tr e at m e nt  c y cl e.   


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 2  of  6 9  
T a bl e  4  
D os e  R e d u cti o ns  of  M ai nt e n a n c e  N a b - p a clit a x el  b as e d  o n  D a y  1 Bl o o d 
C o u nts  
E v e nt  
M a n a g e m e nt 
D os e  M o difi c ati o n  
N e ut r o p e ni a   
 
N a b - p a clit a x el 
A N C  ≥ 1 5 0 0/ µ L 
A d mi nist er  d os e 
N o  d os e r e d u cti o n  
< 1 5 0 0/ µ L 
D el a y  d os e  till  A N C  > 
1 5 0 0/ µ L  
1  d os e l e v el r e d u cti o n  
T h r o m b o c yt o p e ni a  
 
 
Pl at el ets 
≥ 1 0 0 , 0 0 0/µ L  
A d mi nist er  d os e  
N o  d os e r e d u cti o n  
Pl at el ets 
< 1 0 0, 0 0 0/ µ L 
D el a y  d os e  1  w e e k  or 
u ntil  pl at el ets  > 
1 0 0, 0 0 0/ µ L  
1  d os e l e v el r e d u cti o n  
 
6. 2   
D os e  M o difi c ati o ns  D u e t o  N o n - H e m at ol o gi c  T o xi cit y 
D os e  m o difi c ati o ns f or  n o n- h e m at ol o gi c t o xi cit y  d uri n g t h e i n d u cti o n  a n d  m ai nt e n a n c e  p h as es 
ar e s u m m ari z e d i n  T a bl e  5 .   D uri n g t h e i n d u cti o n  p h as e, if t h e t o xi cit y is  cl e arl y r el at e d t o  1  of 
t h e stu d y  dr u gs,  m o difi c ati o n  will  b e  m a d e  o nl y i n t h e  d os e  of t h at  dr u g.   H o w e v er,  d os es  of  b ot h 
dr u gs  will  b e  d e cr e as e d if t h e t o xi cit y  c a n n ot  b e  c o nfi d e ntl y  attri b ut e d t o j ust  1  of t h e st u d y 
dr u gs.  
If t o xi cit y  h as  n ot i m pr o v e d t o Gr a d e  ≤ 1   aft er  3  w e e ks tr e at m e nt  d el a y, t h e  dr u g r es p o nsi bl e f or 
t h e t o xi cit y  will  b e  dis c o nti n u e d.   D uri n g t h e i n d u cti o n  p h as e, if t h e  p ati e nt is j u d g e d t o  b e 
b e n efiti n g fr o m tr e at m e nt, st u d y tr e at m e nt  m a y  c o nti n u e  wit h t h e r e m ai ni n g st u d y  dr u g.   
If t o xi cit y re c urs  aft er  2  d os e r e d u cti o ns  h a v e  alr e a d y  b e e n  m a d e, t h e  dr u g  will  b e  dis c o nti n u e d.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 3  of  6 9  
T a bl e  5    
D os e  R e d u cti o ns f o r  G r a d e  3  o r  4  N o n- H e m at ol o gi c  T o xi citi es  
T o xi cit y  G r a d e  
N a b -p a clit a x el a 
G e m cit a bi n e a 
Gr a d e  0,  1,  or  2  
N o n e  
N o n e  
Gr a d e  3  or  4 b 
H ol d a 
H ol d a 
  T o xi cit y r es ol v es t o  Gr a d e   ≤ 1  
R e d u c e  t h e  d os e  of t h e  off e n di n g  a g e nt  or  a g e nts  b y  1  d os e l e v el 
(T a bl e  1 )  
S e c o n d i n ci d e n c e  of  Gr a d e  3  or  4 
t o xi cit yb 
H ol d a 
H ol d a 
T o xi cit y r es ol v es t o  Gr a d e  ≤ 1  
R e d u c e  t h e  d os e  of t h e  off e n di n g  a g e nt  or  a g e nts  b y  1  a d diti on al 
d os e l e v el ( T a bl e  1 )c 
a B ot h  dr u gs s h o ul d  b e  h el d  a n d t h e  p ati e nt s h o ul d  b e s e e n  w e e kl y  u ntil t o xi cit y r es ol v es t o  ≤  Gr a d e  1.   P ati e nts  w h o  d e v el o p 
irr e v ersi bl e  Gr a d e  3/ 4  n o n-h e m at ol o gi c  t o xi cit y,  or t o xi cit y t h at  d o es  n ot r es ol v e t o  ≤  Gr a d e  1  wit hi n  3  w e e ks , s h o ul d h a v e t h e 
off e n di n g  a g e nt(s)  dis c o nti n u e d.   
b D os e  m o difi c ati o n f or  Gr a d e  3/ 4  n a us e a,  v o miti n g,  or  di arr h e a  will  b e  m a d e  o nl y if t h es e t o xi citi es  o c c ur i n s pit e  of  m a xi m al 
m e di c al  pr o p h yl a xis/ m a n a g e m e nt  
c N o  m or e t h a n  2  d os e r e d u cti o ns  of  n a b -p a clit a x el  a n d  g e m cit a bi n e  ar e  all o w e d.  
7.   
S T U D Y  A S S E S S M E N T S  A N D  E V A L U A TI O N S  
7. 1   
O v e r vi e w  
All  p ati e nts s h o ul d  visit t h e st u d y  c e nt er  o n t h e  d a ys s p e cifi e d  wit hi n t his  pr ot o c ol.   T h e 
c o m pl et e  S c h e d ul e  of  Ass ess m e nts f or t his st u d y is s h o w n i n  A p p e n di x  D .   
7. 2   
B as eli n e  St u d y  Ass ess m e nts  
T h e f oll o wi n g i nf or m ati o n  will  b e  c oll e ct e d  a n d  pr o c e d ur es  will  b e  p erf or m e d f or  e a c h  p ati e nt  at 
s cr e e ni n g: 
Wit hi n  3 0- D a ys  p ri o r t o i niti ati o n  of t r e at m e nt 
•   Writt e n i nf or m e d  c o ns e nt  pri or t o  a n y  ot h er st u d y- r el at e d  pr o c e d ur es 
•   M e di c al  hist or y  
•   P h ysi c al  e x a mi n ati o n  a n d  m e as ur e m e nts  of  h ei g ht (first  visit)  a n d  w ei g ht)  
•   Vit al si g ns (r esti n g  h e art r at e,  bl o o d  pr ess ur e [ B P], r es pir at or y r at e,  a n d t e m p er at ur e 
•   E C O G  p erf or m a n c e st at us  
•   Si n gl e  1 2-l e a d  E C G  
•   S m o ki n g  hist or y 
•   R e vi e w  of  al l m e di c ati o ns  
•   C T s c a ns  of t h e  c h est,  a b d o m e n   a n d  p el vis  
•   B o n e  S c a n   or  P E T s c a n ( o nl y i n  p ati e nts  wit h si g ns/s y m pt o ms s u g g esti v e  of  b o n e 
m et ast as es)   
•   Ar c hi v e d t u m or tiss u e  or  1 5  u nst ai n e d sli d es  of  5  µ M t hi c k n ess s e cti o ns  m a y   b e  o bt ai n e d 
pr ef er a bl y  pri or t o  e n d  of  C y cl e  1,  if  a v ail a bl e  a n d if t h e  p ati e nt  gi v es  c o ns e nt 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 4  of  6 9  
Wit hi n 1 4- D a ys  p ri o r t o i niti ati o n  of t r e at m e nt 
•   C o m pl et e  bl o o d  c o u nt ( C B C)  wit h  3- p art  diff er e nti al  a n d  pl at el ets  ( m ust  b e  p erf or m e d 
wit hi n   7 2  h o urs  pri or t o tr e at m e nt) 
•   F asti n g  c o m pr e h e nsi v e  m et a b oli c  pr ofil e ( C M P) t o i n cl u d e:  gl u c os e,  bl o o d  ur e a  nitr o g e n 
( B U N),  cr e ati ni n e, s o di u m,  p ot assi u m,  c hl ori d e,  c al ci u m,  c ar b o n  di o xi d e ( C O 2 ),  al k ali n e 
p h os p h at as e ( A L P),  A S T,  A L T, t ot al  bilir u bi n, t ot al  pr ot ei n,  a n d  al b u m i n 
•   Pr ot hr o m bi n  ti m e ( P T)  or i nt er n ati o n al  n or m ali z e d r ati o (I N R) 
•   Uri n e  di psti c k  f or  p H,  pr ot ei n,  gl u c os e,  bl o o d,  k et o n es, l e u c o c yt es 
•   F or  W o C B P , ser u m  or  u ri n e  pr e g n a n c y t est ( m ust  b e  p erf or m e d  wit hi n  7 2  h o urs  pri or t o 
t h e i niti ati o n  of tr e at m e nt) 
7. 3   
St u d y  T r e at m e nt  Ass ess m e nts   
7. 3. 1   
I n d u cti o n  T h e r a p y  wit h  N a b -p a clit a x el/ G e m cit a bi n e   
D a y  1  of  e a c h  c y cl e 
•   U p d at e  of  m e di c al  hist or y 
•   P h ysi c al  e x a mi n ati o n  (i n cl u di n g  w ei g ht) 
•   Vit al si g ns  
•   E C O G  p erf or m a n c e st at us  
•   C B C, i n cl u di n g  3- p art  diff er e nti al  a n d  pl at el ets ( m ust  b e  p erf o r m e d  wit hi n  7 2  h o urs  pri or 
t o tr e at m e nt) 
•   Cli ni c al  c h e mistr y ( C M P ) ( m ust  b e  p erf or m e d  wit hi n  7 2  h o urs  pri or t o tr e at m e nt) 
•   F or  W o C B P , s er u m  or  uri n e  pr e g n a n c y t est ( m ust  b e  p erf or m e d  wit hi n  7 2  h o urs  pri or t o 
tr e at m e nt) 
•   A E  ass ess m e nt  
•   C o n c o mit a nt  m e di c ati o n r e vi e w  
•   St u d y  dr u gs i nf usi o n 
D a y  8  of  e a c h  c y cl e  
•   C B C, i n cl u di n g  3- p art  diff er e nti al  a n d  pl at el ets  
•   St u d y  dr u g i nf usi o n  
7. 3. 2   
M ai nt e n a n c e  T h e r a p y  wit h  Si n gl e -A g e nt  N a b - p a clit a x el  
D a y  1  of  e a c h  c y cl e 
•   U p d at e  of  m e di c al  hist or y 
•   P h ysi c al  e x a mi n ati o n  (i n cl u di n g  w ei g ht) 
•   V it al si g ns 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 5  of  6 9  
•   E C O G  p erf or m a n c e st at us  
•   C B C, i n cl u di n g  3- p art  diff er e nti al  a n d  pl at el ets  ( m ust  b e  p erf or m e d  wit hi n  7 2  h o urs  pri or 
t o tr e at m e nt) 
•   C M P  ( m ust  b e  p erf or m e d  wit hi n  7 2  h o urs  pri or t o tr e at m e nt) 
•   F or  W o C B P , s er u m  or  uri n e  pr e g n a n c y t est ( m ust  b e  p erf orm e d  wit hi n  7 2  h o urs  pri or t o 
tr e at m e nt) 
•   C o n c o mit a nt  m e di c ati o n r e vi e w  
•   A E  ass ess m e nt  
7. 3. 3   
R es p o ns e  Ass ess m e nt  E v e r y  3  C y cl es  ( ±  7  d a ys) 
P ati e nts  will  b e  e v al u at e d f or r es p o ns e t o tr e at m e nt  aft er  e v er y  3  c y cl es  of tr e at m e nt.   T h e 
f oll o wi n g  ass ess m e nts  will  b e  p erf or m e d:  
•   C T s c a ns  of  c h est,  a b d o m e n  a n d  p el vis  ( at r est a gi n g,  o nl y s c a ns t h at  w er e  a b n or m al  at 
b as eli n e  n e e d t o  b e r e p e at e d  u nl ess  a d diti o n al  ar e as  ar e  cli ni c all y i n di c at e d )  
•   B o n e  S c a n  or  P E T (if  p ositi v e  at  b as eli n e, r e p e at  e v er y  6  c y cl es  of t h er a p y)  
P ati e nts  wit h  pr o gr essi v e  dis e as e  ( P D) or  u n a c c e pt a bl e t o xi cit y s h o ul d  b e  dis c o nti n u e d fr o m 
st u d y tr e at m e nt;  p ati e nts  wit h S D   or r es p o ns e t o t h er a p y  will  c o nti n u e tr e at m e nt. 
7. 4   
E n d  of  St u d y  E v al u ati o n (t o  b e  c o m pl et e d  wit hi n  3 0  d a ys  of t r e at m e nt 
dis c o nti n u ati o n)  
All  p ati e nts  m ust  b e s e e n  a n d  e v al u at e d  wit hi n  3 0  d a ys  aft er st o p pi n g st u d y tr e at m e nt.   If 
tr e at m e nt is  dis c o nti n u e d  b e c a us e  of t o xi cit y  or  a n y  ot h er r e as o n(s)  at  a tr e at m e nt  visit  a n d  n o 
st u d y tr e at m e nt is  a d mi nist er e d, t h at  visit  m a y f ulfil t h e  E n d - of-Tr e at m e nt  Visit.    Pati e nts  m ust 
b e f oll o w e d f or  A Es f or  3 0  c al e n d ar  d a ys  aft er t h e l ast  d os e  of st u d y  dr u g.   
•   U p d at e  of  m e di c al  hist or y 
•   P h ysi c al  e x a mi n ati o n   
•   V it al si g ns 
•   E C O G  p erf or m a n c e st at us  
•   C B C, i n cl u di n g  3- p art  diff er e nti al  a n d  pl at el ets   
•   C M P   
•   F or  W o C B P , s er u m  or  uri n e  pr e g n a n c y t est  
•   C o n c o mit a nt  m e di c ati o n r e vi e w  
•   A E  ass ess m e nt  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 6  of  6 9  
7. 5   
F oll o w- u p   
7. 5. 1   
F oll o w- u p  p ri o r t o  dis e as e  p r o g r essi o n  e v e r y  6  w e e ks  ( ±  7  d a ys): 
P ati e nts  w h o  dis c o nti n u e st u d y tr e at m e nt  wit h o ut  e vi d e n c e  of  dis e as e  pr o gr essi o n s h o ul d  b e 
f oll o w e d if  p ossi bl e t o  d et er mi n e t h e  d at e  of  pr o gr essi o n.   T h e f oll o wi n g  ass ess m e nts  will t a k e 
pl a c e:  
•   U p d at e  of  m e di c al  hist or y 
•   P h ysi c al  e x a mi n ati o n   
•   V it al si g ns 
•   E C O G  p erf or m a n c e st at us  
•   C T s c a ns  of  c h est,  a b d o m e n  a n d  p el vis  ( o nl y s c a ns t h at  ar e  a b n or m al  at  b as eli n e  n e e d t o 
b e r e p e at e d,  u nl ess  a d diti o n al  ar e as  ar e  cli ni c all y i n di c at e d)  
•   B o n e  S c a n  or  P E T s c a n ( o nl y if  a b n or m al  at  b as eli n e)  
7. 5. 2   
F oll o w- u p  aft e r  dis e as e  p r o g r essi o n (s u r vi v al f oll o w  u p) 
Aft er  dis e as e  pr o gr essi o n is  d o c u m e nt e d,  p ati e nts  will  b e f oll o w e d  e v er y  3  m o nt hs f or s ur vi v al 
(i. e.,  d at e  a n d  c a us e  of  d e at h) f or t h e first  y e ar,  a n d t h e n  e v er y  6  m o nt hs t h er e aft er  u p t o  5  y e ars 
or  d e at h  w hi c h e v er  c o m es first.   P ati e nts  m a y  b e  c o nt a ct e d  d uri n g  o ut p ati e nt  visits  or  b y 
t el e p h o n e. 
8.   
D R U G  F O R M U L A TI O N,  A V AI L A BI LI T Y,  A D MI NI S T R A TI O N,  A N D 
T O XI CI T Y I N F O R M A TI O N  
St u d y  D r u g  
D os a g e  F o r m  a n d  St r e n gt h 
M a n uf a ct u r e r  
N a b -p a clit a x el   
( A br a x a n e  or A BI -0 0 7)  
E a c h  vi al  c o nt ai ns  1 0 0  m g  of  p a clit a x el  a n d 
a p pr o xi m at el y  9 0 0  m g  of  h u m a n  al b u mi n   
C el g e n e  
G e m cit a bi n e  ( G e m z ar)   
E a c h  vi al  c o nt ai ns  2 0 0  m g/  1  g m  
Eli  Lill y  a n d  C o m p a n y  
 
8. 1   
N a b - p a clit a x el  
8. 1. 1   
L a b eli n g,  P a c k a gi n g,  a n d  S u p pl y   
N a b -p a clit a x el  will  b e s u p pli e d  b y  C el g e n e.  
T h e i m m e di at e  p a c k a gi n g  will  c o nt ai n  a st at e m e nt t o  c o nf or m  wit h  F D A I n v esti g ati o n al  N e w 
Dr u g (I N D) r e q uir e m e nts  as f oll o ws :  C a uti o n:  N e w  Dr u g - Li mit e d  b y  F e d er al ( or  U nit e d  St at es) 
l a w t o i n v esti g ati o n al  us e. 
All st u d y  dr u gs  m ust  b e  k e pt i n  a s e c ur e  pl a c e  u n d er  a p pr o pri at e st or a g e  c o n diti o ns.   St or a g e 
c o n diti o ns f or  n a b- p a clit a x el  ar e i n cl u d e d  o n t h e i n v esti g ati o n al  pr o d u ct  l a b el. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 7  of  6 9  
 
8. 1. 2   
P r e p a r ati o n  a n d  A d mi nist r ati o n 
N a b - p a clit a x el is  pr e p ar e d  a n d  a d mi nist er e d  as  a n I V i nf usi o n  p er i nstit uti o n al st a n d ar d. 
N o  pr e m e di c ati o n t o  pr e v e nt  h y p ers e nsiti vit y r e a cti o ns is r e q uir e d  pri or t o  a d mi nistr ati o n  of  n a b-
p a clit a x el.   H o w e v er, if  a  mi l d  or  m o d er at e  h y p ers e nsiti vit y r e a cti o n  o c c urs, t h e  p ati e nt  m a y  b e 
pr e m e di c at e d  p er i nstit uti o n al st a n d ar d. 
8. 1. 3   
P r e c a uti o ns  a n d  Ris ks  
Pr e c a uti o ns  a n d ris ks  ar e l o c at e d i n t h e I B. 
8. 2   
G e m cit a bi n e  
G e m cit a bi n e  is t o  b e  a d mi nist er e d i n  a c c or d a n c e  wit h t h e t er ms  of its  m ar k eti n g  a ut h ori z ati o n 
a n d i n  a c c or d a n c e  wit h i nstit uti o n al st a n d ar d  of  pr a cti c e.   Pl e as e r ef er t o t h e  U S  P a c k a g e I ns ert  
( U S PI) (htt p:// pi.lill y. c o m/ us/ g e m z ar. p df ) f or  d et ail e d i nf or m ati o n  o n  h o w t o  pr ep ar e  a n d 
a d mi nist er  g e m cit a bi n e.  
8. 2. 1   
L a b eli n g,  P a c k a gi n g,  a n d  S u p pl y  
E a c h sit e  will  pr o c ur e  a s u p pl y  of  g e m cit a bi n e ,  w hi c h is  c o m m er ci all y  a v ail a bl e. 
All st u d y  m e di c ati o ns  m ust  b e  k e pt i n  a s e c ur e  pl a c e  u n d er  a p pr o pri at e st or a g e  c o n diti o ns.  
St or a g e  c o n diti o ns  f or g e m cit a bi n e   c a n  b e f o u n d i n t h e r el e v a nt U S PI .   T h e  e x pir ati o n  d at e  o n 
t h e l a b el  m ust  n ot  b e  e x c e e d e d. 
T h e  S p o ns or  or its r e pr es e nt ati v es  m ust  b e  gr a nt e d  a c c ess  o n r e as o n a bl e r e q u est t o  c h e c k  dr u g 
st or a g e,  dis p e nsi n g  pr o c e d ur es,  a n d  a c c o u nt a bilit y r e c or ds. 
8. 2. 2   
P r e p a r ati o n  a n d  A d mi nist r ati o n   
Pl e as e r ef er t o t h e  U S PI  f or  d et ail e d i nf or m ati o n  o n  h o w t o  pr e p ar e  a n d  a d mi nist er  g e m cit a bi n e 
8. 2. 3   
P r e c a uti o ns  a n d  Ris ks  
Pl e as e r ef er t o t h e  U S PI  f or  d et ail e d i nf or m ati o n  o n t h e ris ks  ass o ci at e d  wit h t h e  us e  of 
g e m cit a bi n e . 
8. 3   
A c c o u nt a bilit y f o r  N a b - p a clit a x el  p r o vi d e d f o r t h e St u d y   
T h e  P ri n ci p al In v esti g at or  ( or  d esi g n e e) is r es p o nsi bl e f or  a c c o u nt a bilit y  of  all  us e d  a n d  u n us e d 
n a b - p a clit a x el  pr o vi d e d f or t his st u d y. 
All i n v e nt ori es  of  n a b- p a clit a x el  pr o vi d e d f or t his st u d y  m ust  b e  m a d e  a v ail a bl e f or i ns p e cti o n  b y 
t h e  S p o ns or or  its r e pr es e nt ati v es  a n d r e g ul at or y  a g e n c y i ns p e ct ors  u p o n r e q u est. 
At t h e  e n d  of t h e st u d y ,  all  S C RI I n n o v ati o ns  Dr u g  A c c o u nt a bilit y  R e c or d  F or m(s)  will  b e 
c o m pl et e d  b y t h e sit e  a n d s e nt t o t h e  S C RI  I n n o v ati o ns R e g ul at or y  D e p art m e nt .   S u p pli es  of  n a b-
p a clit a x el  pr o vi d e d f or t his st u d y  m ust  n ot  b e  d estr o y e d  u nl ess  pri or  a p pr o v al  h as  b e e n  gr a nt e d 
b y t h e  S p o ns or  or its r e pr es e nt ati v e.   Pl e as e  c o nt a ct  S C RI I n n o v ati o ns r e g ar di n g  dis p os al  of  a n y 
n a b -p a clit a x el  pr o vi d e d f or t his st u d y. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 8  of  6 9  
9.   
R E S P O N S E  E V A L U A TI O N S  A N D  M E A S U R E M E N T S  
R es p o ns e  a n d  pr o gr essi o n  will  b e  e v al u at e d i n t his st u d y  usi n g t h e  R es p o ns e  E v al u ati o n  Crit eri a 
i n  S oli d  T u m ors ( R E CI S T)  V ersi o n  1. 1 (s e e A p p e n di x  E ).   L esi o ns  ar e  eit h er  m e as ur a bl e  or  n o n-
m e as ur a bl e  a c c or di n g t o t h e  crit eri a.   All  p ati e nts  p arti ci p ati n g i n t his st u d y  will  h a v e  m e as ur a bl e 
l esi o ns  p er  R E CI S T  V ersi o n  1. 1.  
1 0.   
S T A TI S TI C A L  C O N SI D E R A TI O N S  
1 0. 1   
St atisti c al  D esi g n  
T h e  p ur p os e  of t his  o p e n-l a b el  n o n-r a n d o mi z e d  p h as e  II tri al is t o st u d y t h e  effi c a c y  a n d t o xi cit y 
of t h e  g e m cit a bi n e/ n a b -p a clit a x el  c o m bi n ati o n f oll o w e d  b y  m ai nt e n a n c e si n gl e -a g e nt  n a b -
p a clit a x el  as t h e first -li n e tr e at m e nt  of  p ati e nts  wit h  a d v a n c e d  U C.   T w o  gr o u ps  of  p ati e nts  will 
b e  eli gi bl e f or t his st u d y:   1)  p ati e nts  w h o  ar e  c o nsi d er e d  p o or  c a n di d at es f or tr e at m e nt  wit h 
cis pl ati n ( Fi g ur e  1 ),  a n d  2)  p ati e nts  wit h  vis c er al  m et ast as es,  w h o  ar e i n c ur a bl e  a n d  u nli k el y t o 
d eri v e l o n g- t er m  b e n efit fr o m tr e at m e nt  wit h  cis pl ati n-b as e d  r e gi m e ns. 
1 0. 2   
S a m pl e  Si z e  C o nsi d e r ati o ns  
T his  will  b e  a n  o p e n- l a b el si n gl e-st a g e  n o n-r a n d o mi z e d P h as e  II tri al t o  e v al u at e t h e  effi c a c y  a n d 
t o xi cit y  of t h e  g e m cit a bi n e/ n a b- p a clit a x el  c o m bi n ati o n f oll o w e d  b y  m ai nt e n a n c e  d os e  of  n a b-
p a clit a x el r e gi m e n.   W e  e x p e ct  a p pr o xi m at el y  8 0 %  of  p ati e nts t o  c o ntri b ut e  a  pr o gr essi o n  e v e nt 
t o t h e  a n al ysis.  T h e  pri m ar y  e n d p oi nt is  6- m o nt h  P F S ( P F S 6). 
W e  h a v e  e vi d e n c e fr o m  a  P h as e  III tri al t h at  g e m cit a bi n e/ c ar b o pl ati n ( a r e gi m e n fr e q u e ntl y 
a d mi nist er e d t o  p ati e nts  c o nsi d er e d  p o or  c a n di d at es f or  cis pl ati n)  pr o d u c e s  a  6- m o nt h  P F S  of 
~ 4 5 % ( S o n p a v d e  et  al.  2 0 1 2 , P o d h aj c er  et  al.  2 0 0 8 ), D e  S a ntis   et  al.  2 0 1 2).  It is  ass u m e d 
t h er ef or e t h at  a  P F S 6  of ≥ 6 5 % i s  a n  o pti m al  esti m at e f or  a  m e a ni n gf ul i m pr o v e m e nt  usi n g t h e 
g e m cit a bi n e/ n a b -p a clit a x el  c o m bi n ati o n  f oll o w e d  b y  m ai nt e n a n c e si n gl e- a g e nt  n a b-p a clit a x el .  
A n i m pr o v e m e nt i n  P F S 6 fr o m  a  hist ori c al  4 5 % t o  6 5 % tr a nsl at es t o  a n  a p pr o xi m at e d  h a z ar d 
r ati o  of  0. 5 4.   A s a m pl e si z e  of  5 5  p ati e nts  will  pr o vi d e  at l e ast  8 0 %  p o w er f or  a  2-si d e d t est f or 
t h e  P F S 6  ass u mi n g  a si g nifi c a n c e l e v el  of  0. 0 5  a n d  a  dr o p- o ut/ n o n-e v al u a bl e r at e  of  n o  m or e 
t h a n  1 0 %  of  p ati e nts (i. e.  5  p ati e nts).   S a m pl e si z e  w as  d et er mi n e d  usi n g  A R TS U R V i n t h e 
st atisti c al  p a c k a g e  S T A T A ( v 1 2).   P o w er  ass ess m e nts  w er e  n ot  c o n d u ct e d f or s e c o n d ar y 
e n d p oi nts. 
1 0. 3   
D at a  A n al ysis 
T h e  d at a b as e, r a n d o mi z ati o n  a n d s af et y  m o nit ori n g  will  b e  m a n a g e d  c e ntr all y  b y  S ar a h  C a n n o n 
R es e ar c h I nstit ut e ( S C RI).    
1 0. 3. 1   
D e m o g r a p hi cs  a n d  B as eli n e  C h a r a ct e risti cs  
D e m o gr a p hi c  a n d  b as eli n e  dis e as e  c h ar a ct eristi cs  will  b e s u m m ari z e d.   D at a t o  b e t a b ul at e d  will 
i n cl u d e  d e m o gr a p hi c f e at ur es s u c h  as  a g e, s e x  a n d r a c e,  as  w ell  as  dis e as e-s p e cifi c 
c h ar a ct eristi cs.  
T h e  n u m b er  a n d  p er c e nt a g es  of  p ati e nts s cr e e n e d, r a n d o mi z e d, tr e at e d,  c o m pl et e d t h e 
tr e at m e nt/st u d y  a n d  wit h dr a w n fr o m tr e at m e nt/st u d y f or  a n y r e as o n  will  b e  pr es e nt e d. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  3 9  of  6 9  
1 0. 3. 2   
Effi c a c y  A n al ysis 
All  pri m ar y  effi c a c y  a n al ys es  will  b e  p erf or m e d  usi n g t h e  p o p ul ati o n  of  p ati e nts  w h o r e c ei v e 
st u d y tr e at m e nt,  a n d  mi ni m u m f oll o w- u p  p eri o d  of  6  m o nt hs  aft er st arti n g t h er a p y  or 
pr o gr essi o n,  w hi c h e v er  c o m es first f or  e a c h  p ati e nt.  T h e r e cr uit m e nt  p eri o d  will  b e  ~ 1 8  m o nt hs. 
Pri m ar y  effi c a c y  e n d p oi nt:  P F S  E v e nt  Fr e e  R at e  at  M o nt h  6  
6- m o nt h  P F S  e v e nt fr e e r at e is  d efi n e d  as t h e  n u m b er  of  p ati e nts  wit h  P F S   > 6  m o nt hs ( or  2 6 
w e e ks t o  a c c o m m o d at e t h e t u m or  ass ess m e nt s c h e d ul e)   di vi d e d  b y  n u m b er  of  p ati e nts  wit h 
b as eli n e t u m or  ass ess m e nt.  
T h e  pri m ar y  e n d p oi nt,  6- m o nt h  P F S  e v e nt fr e e r at e,  will  b e  pr es e nt e d  as t h e  p oi nt  esti m at e  wit h 
its  ass o ci at e d  9 5 %  Cl o p p er-P e ars o n  c o nfi d e n c e i nt er v al ( CI).  
S e c o n d ar y  Effi c a c y  E n d p oi nts:  
Effi c a c y  a n al ys es  will  als o  b e  p erf or m e d  o n t h e  2  p ati e nt s u b gr o u ps  eli gi bl e f or t his tri al (i. e. 
p ati e nts  w h o  ar e  cis pl ati n -i n eli gi bl e  a n d  p ati e nts  wit h  p o or  pr o g n osis  d u e t o  vis c er al  m et ast as es). 
•   O v er all  R es p o ns e  R at e ( O R R) is  d efi n e d  as t h e  pr o p orti o n  of  p ati e nts  wit h  c o nfir m e d 
c o m pl et e r es p o ns e ( C R ) or  p arti al r es p o ns e ( P R ) a c c or di n g t o  R E CI S T  v 1. 1 .  
 
•   Cli ni c al  B e n efit  R at e ( C B R) is  d efi n e d  as  t h e  pr o p orti o n  of  p ati e nts  wit h  C R,  P R  or  S D 
a c c or di n g t o  R E CI S T  v 1. 1. 
 
o   F or  O R R  a n d  C B R,  p ati e nts  wit h o ut  a  p ost- b as eli n e t u m or  ass ess m e nt  will  b e 
cl ass e d  as  n ot  e v al u a bl e ( N E)  a n d  c o nsi d er e d  as  n o n -r es p o n d ers. 
 
•   Pr o gr essi o n  Fr e e  S ur vi v al ( P F S)  is  d efi n e d as t h e ti m e fr o m t h e first  d a y  of st u d y  dr u g 
a d mi nistr ati o n ( D a y  1) t o  dis e as e  pr o gr essi o n  as  d efi n e d  b y t h e  R E CI S T  v 1. 1  crit eri a,  or 
d e at h  o n st u d y,  w hi c h e v er  c o m es first .   P ati e nts  w h o  ar e  ali v e  a n d fr e e fr o m  dis e as e 
pr o gr essi o n  will  b e  c e ns or e d  at t h e  d at e  of l ast t u m or  ass ess m e nt.  
 
•   O v er all  S ur vi v al ( O S)  is  d efi n e d  as t h e ti m e fr o m t h e first  d a y  of st u d y  dr u g 
a d mi nistr ati o n ( D a y  1)  or  d e at h  o n st u d y.   P ati e nts  w h o  ar e  ali v e  will  b e  c e ns or e d  at l ast 
k n o w n  d at e  ali v e. 
F or  O R R  a n d  C B R, t h e  esti m at es  a n d t h e  ass o ci at e d  9 5 %  CI  ( b as e d  o n t h e  Cl o p p er-P e ars o n 
m et h o d) f or t h e  e ntir e  tr eat m e nt  gr o u p  will  b e  c al c ul at e d .   T h e  O R R  a n d  C B R  will  als o  b e 
c al c ul at e d f or t h e  2  p ati e nt s u b gr o u ps. 
F or  P F S  a n d  O S,  K a pl a n- M ei er  c ur v es  will  b e  g e n er at e d  a n d t h e  m e di a n ti m e t o  e v e nt  a n d t h e 
ass o ci at e d  9 5 %  CI   b e  pr o vi d e d.   C ur v es  will  b e  g e n er at e d f or t h e  e ntir e tr e at m e nt  p o p ul ati o n, 
a n d f or t h e  2  eli gi bl e s u b gr o u ps  of  p ati e nts. 
1 0. 3. 3   
S af et y  A n al ysis 
All  p ati e nts  w h o r e c ei v e  at l e ast  1  d os e  of st u d y tr e at m e nt  will  b e i n cl u d e d i n t h e s af et y 
p o p ul ati o n.   S af et y  will  b e  ass ess e d t hr o u g h t h e  a n al ysis  of t h e r e p ort e d i n ci d e n c e  of tr e at m e nt -


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 0  of  6 9  
e m er g e nt  A Es.   Tr e at m e nt - e m er g e nt  A Es  ar e t h os e  wit h  a n  o ns et  o n  or  aft er t h e i niti ati o n  of 
t h er a p y,  a n d  will  b e  gr a d e d  a c c or di n g t o  N CI  C T C A E  v 4. 0 3.   A  c op y  of  C T C A E s c ori n g s yst e m 
m a y  b e  d o w nl o a d e d fr o m: ( htt p:// e vs. n ci. ni h. g o v/ft p 1/ C T C A E/ C T C A E _ 4. 0 3 _ 2 0 1 0- 0 6-
1 4 _ Q ui c k R ef er e n c e _ 8. 5 x 1 1. p df ) 
T h e  A Es  will  b e  c o d e d  u si n g  M e di c al  Di cti o n ar y f or  R e g ul at or y  A cti viti es ( M e d D R A),  a n d 
s u m m ari z e d  usi n g s yst e m  or g a n  cl ass  a n d  pr ef err e d t er m f or  all  p ati e nts i n t h e  S af et y  P o p ul ati o n.  
I n  a d diti o n, s u m m ari es  of  S A Es,  A Es l e a di n g t o tr e at m e nt  dis c o nti n u ati o n,  A Es  b y  m a xi m u m 
N CI  C T C A E  gr a d e,  a n d  A Es r el at e d t o st u d y tr e at m e nt  will  als o  b e  pr es e nt e d  f or  all  p ati e nts i n 
t h e  S af et y P o p ul ati o n. 
Ot h er s af et y  e n d p oi nts, i n cl u di n g l a b or at or y r es ults,  will  b e s u m m ari z e d f or  all  p ati e nts i n t h e 
S af et y  P o p ul ati o n.  
1 0. 3. 4   
C o r r el ati v e  St u di es  
T u m or  tiss u e fr o m  ar c hi v al  bi o psi es  will  b e  c oll e ct e d t o  b e  c e ntr all y st u di e d i n t h e f ut ur e.  
G e n o mi c  D N A  will  b e  is ol at e d  usi n g  P h e n ol: C hl or of or m  e xtr a cti o n  b y st a n d ar d m ol e c ul ar 
bi ol o g y t e c h ni q u es.   ds D N A  will  b e  q u a ntifi e d  a n d  D N A  q u alit y  ass ess m e nt  will  b e  p erf or m e d 
b y  g el  el e ctr o p h or esis.   R N A  will  b e   h ar v est e d  usi n g t h e  Qi a g e n  R N A e as y  kit  a n d  q u alit y  of 
R N A  will  b e   c o nfir m e d b y  m e as uri n g t h e  2 6 0/ 2 8 0 r ati o  usi n g  n a n o dr o p.   Pr ot ei n  ass a ys  pl a n n e d 
f or t his st u d y  will i n cl u d e i m m u n o hist o c h e mistr y (I H C) f or  S P A R C  e x pr essi o n.  D N A  a n d  R N A 
e v al u ati o ns  f or t his st u d y  will i n cl u d e  N e xt  G e n er ati o n  S e q u e n ci n g  a n d  N a n ostri n g  g e n e 
e x pr essi o n t o  e v al u at e  g e n es i n t h e  P a n C a n  p a n el  of  7 7 0  ess e nti al  c a n c er  p at h w a y  a n d  dri v er 
g e n es .   F or  a n al ysis  of  g e n e s e q u e n ci n g, r a w s e q ue n c e  d at a i n  F ast q f or m at  will  b e   ali g n e d t o 
h u m a n r ef er e n c e  g e n o m e  a n d  q u a ntifi e d  a n d  c o m p ar e d.   Di git al r a w  c o u nts  of  R N A  a b u n d a n c e 
b y  N a n ostri n g  will  b e   n or m ali z e d  usi n g i nt er n al  c o ntr ols  a n d  h o us e k e e pi n g  g e n es.  P at h w a y 
a n al ysis  will  b e   p erf or m e d  usi n g I n g e n uit y  P at h w a y  A n al ysis (I P A) s oft w ar e.  T h e I H C f or 
S P A R C  a n d  g e n e  e x pr essi o n  a n d s e q u e n ci n g  d at a  will  b e  e x a mi n e d f or t h eir  ass o ci ati o n  wit h 
P F S,  O R R  a n d  O S.  T h e  ass o ci ati o n  of I H C  a n d  g e n o mi c st u di es  wit h  P F S,  O S  a n d r es p o ns e  will 
b e  e x a mi n e d  usi n g  C o x r e gr essi o n.    
1 0. 4   
A n al ysis  Ti m e  P oi nts  
1 0. 4. 1   
Fi n al  A n al ysis  
T h e fi n al  a n al ysis  of t h e st u d y  will  o c c ur  aft er  5 5  p ati e nts  ar e  e nr oll e d  a n d  at l e ast  4 0  h a v e 
e x p eri e n c e d  dis e as e  pr o gr essi o n.  
1 0. 4. 2   
Pl a n n e d I nt e ri m  A n al ysis  
T h er e  will  b e  n o  pl a n n e d i nt eri m  a n al ysis.  
1 0. 4. 3   
S af et y  R e vi e w  
T h er e  will  b e  n o  pl a n n e d i nt eri m s af et y r e vi e ws.  
1 0. 4. 4   
Effi c a c y  R e vi e w  
T h er e  will  b e  n o  pl a n n e d i nt eri m  a n al ys es  of tr e at m e nt  effi c a c y.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 1  of  6 9  
1 1.   
S A F E T Y  R E P O R TI N G  A N D  A N A L Y S E S  
S af et y  ass ess m e nts  will  c o nsist  of  m o nit ori n g  a n d r e c or di n g  pr ot o c ol- d efi n e d  A Es  a n d  S eri o us 
A d v ers e  E v e nt s ( S A Es),  m e as ur e m e nt  of  pr ot o c ol- s p e cifi e d  h e m at ol o g y,  cli ni c al  c h e mistr y,  a n d 
ot h er  pr ot o c ol- s p e cifi e d t ests t h at  ar e  d e e m e d  criti c al t o t h e s af et y  e v al u ati o n  of t h e st u d y  dr u g.  
T h e  Pri n ci p al I n v esti g at or is r es p o nsi bl e f or r e c o g ni zi n g  a n d r e p orti n g  A Es t o t h e  S C RI 
I n n o v ati o ns S af et y  D e p art m e nt (s e e  S e cti o n  1 1. 1. 5 ).  It is t h e  S p o ns or’s r es p o nsi bilit y t o r e p ort 
r el e v a nt  S A Es t o t h e  a p pli c a bl e l o c al,  n ati o n al,  or i nt er n ati o n al r e g ul at or y  b o di es.  I n  a d diti o n, 
I n v esti g at ors  m ust r e p ort  S A Es  a n d f oll o w- u p i nf or m ati o n t o t h eir r es p o nsi bl e I R B/ E C  a c c or di n g 
t o t h e  p oli ci es  of t h at I R B/ E C.  
  T h e  Pri n ci p al I n v esti g at or is  als o r es p o nsi bl e f or  e ns uri n g t h at  e v er y st aff  m e m b er i n v ol v e d i n 
t h e st u d y is f a mili ar  wit h t h e  c o nt e nt  of t his s e cti o n. 
1 1. 1   
D efi niti o ns    
1 1. 1. 1   
A d v e rs e  E v e nts  
A d v ers e  e v e nt  m e a ns  a n y  u nt o w ar d  m e di c al  o c c urr e n c e  ass o ci at e d  wit h t h e  us e  of  a  dr u g i n 
h u m a ns,  w h et h er  or  n ot  c o nsi d er e d  dr u g r el at e d.   A n  A E  ( als o  k n o w n  as  a d v ers e  e x p eri e n c e)  c a n 
b e  a n y  u nf a v or a bl e  a n d  u ni nt e n d e d si g n ( e. g.,  a n  a b n or m al l a b or at or y fi n di n g), s y m pt o m,  or 
dis e as e t e m p or aril y  ass o ci at e d  wit h t h e  us e  of  a  dr u g,  wit h o ut  a n y  j u d g m e nt a b o ut  c a us alit y.   A n 
A E   c a n  aris e  wit h  a n y  us e  of t h e  dr u g ( e. g.,  off-l a b el  us e,  us e i n  c o m bi n ati o n  wit h  a not h er  dr u g) 
a n d  wit h  a n y r o ut e  of  a d mi nistr ati o n, f or m ul ati o n,  d os e  or i n cl u di n g  o v er d os e. 
1 1. 1. 2   
S e ri o us  A d v e rs e  E v e nt  
A n  A E  o r  a s us p e ct e d  a d v e rs e  r e a cti o n ( S A R) is  c o nsi d e r e d  “s e ri o us ” if it  r es ults i n  a n y  of 
t h e f oll o wi n g  o ut c o m es: 
•   D e at h  
•   A lif e -t h r e at e ni n g  A E 
•   I n p ati e nt  h os pit ali z ati o n  of  at l e ast  2 4- h o u rs  o r  p r ol o n g ati o n  of  e xisti n g 
h os pit ali z ati o n 
•   A  p e rsist e nt  o r si g nifi c a nt i n c a p a cit y  o r s u bst a nti al  dis r u pti o n  of t h e  a bilit y t o 
c o n d u ct  n o r m al lif e f u n cti o ns  
•   A  c o n g e nit al  a n o m al y/ bi rt h  d ef e ct 
I m p ort a nt  m e di c al e v e nts t h at  m a y  n ot r es ult i n  d e at h,  b e lif e -t hr e at e ni n g,  or r e q uir e 
h os pit ali z ati o n  m a y  b e  c o nsi d er e d s eri o us  w h e n,  b as e d  u p o n  a p pr o pri at e  m e di c al j u d g m e nt, t h e y 
m a y j e o p ar di z e t h e  p ati e nt  or s u bj e ct  a n d  m a y r e q uir e  m e di c al  or s ur gi c al i nt er v e nti o n t o  pr e v e nt 
o n e  of t h e  o ut c o m es list e d i n t his  d efi niti o n.   E x a m pl es  of s u c h  m e di c al  e v e nts i n cl u d e  all er gi c 
br o n c h os p as m r e q uiri n g i nt e nsi v e tr e at m e nt i n  a n  e m er g e n c y r o o m  or  at  h o m e,  bl o o d  d ys cr asi as 
or  c o n v ulsi o ns t h at  d o  n ot r es ult i n  h os pit ali z ati o n,  or  d e v el o p m e nt  of  dr u g  d e p e n d e n c y  or  dr u g 
a b us e.   
It is i m p ort a nt t o  disti n g uis h  b et w e e n  “s eri o us ”  a n d  “s e v er e ”  A E,  as t h e t er ms  ar e  n ot 
s y n o n y m o us.   S e v erit y is  a  m e as ur e  of i nt e nsit y;  h o w e v er,  a n  A E  of s e v er e i nt e nsit y  n e e d  n ot 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 2  of  6 9  
n e c ess aril y  b e  c o nsi d er e d s eri o us.   S eri o us n ess s er v es  as t h e  g ui d e f or  d efi ni n g r e g ul at or y 
r e p orti n g  o bli g ati o ns.   “ S eri o us ” is  a r e g ul at or y  d efi niti o n  a n d is  b as e d  o n  p ati e nt/ e v e nt  o ut c o m e 
or  a cti o n  us u all y  ass o ci at e d  wit h  e v e nts t h at  p os e  a t hr e at t o  a  p ati e nt’s lif e  or  vit al f u n cti o ns.  
F or  e x a m pl e,  n a us e a  w hi c h  p ersists f or s e v er al  h o urs  m a y  b e  c o nsi d er e d s e v er e  n a us e a,  b ut  m a y 
n ot  b e  c o nsi d er e d  a n  S A E.   O n t h e  ot h er  h a n d,  a str o k e  w hi c h r es ults i n  o nl y  a li mit e d  d e gr e e  of 
dis a bilit y  m a y  b e  c o nsi d er e d  o nl y  a  mil d str o k e,  b ut  w o ul d  b e  c o nsi d er e d  a n  S A E.   S e v erit y  a n d 
s eri o us n ess s h o ul d  b e i n d e p e n d e ntl y  ass ess e d  w h e n r e c or di n g  A Es  o n t h e  e C R F  a n d  S A Es  o n t h e 
S A E  R e p ort  F or m. 
1 1. 1. 3   
A d v e rs e  R e a cti o n  
A n  a d v ers e r e a cti o n  m e a ns  a n y  A E  c a us e d  b y  a  dr u g.   A d v ers e r e a cti o ns  ar e  a s u bs et  of  all 
s us p ect e d  a d v ers e r e a cti o ns  ( S A Rs)  w h er e t h er e is  a r e as o n t o  c o n cl u d e t h at t h e  dr u g  c a us e d t h e 
e v e nt.  
1 1. 1. 4   
S us p e ct e d  A d v e rs e  R e a cti o n  
S us p e ct e d  a d v ers e r e a cti o n  m e a ns  a n y  A E  f or  w hi c h t h er e is  a r e as o n a bl e  p ossi bilit y t h at t h e 
dr u g  c a us e d t h e  A E .   R e as o n a bl e  p ossi bilit y  m e a ns t h at t h er e is  e vi d e n c e t o s u g g est  a  c a us al 
r el ati o ns hi p  b et w e e n t h e  dr u g  a n d t h e A E .   A s us p e ct e d  a d v ers e r e a cti o n i m pli es  a l ess er  d e gr e e 
of  c ert ai nt y  a b o ut  c a us alit y t h a n  a d v ers e r e a cti o n,  w hi c h  m e a ns  a n y  A E  c a us e d  b y  a  dr u g.  
1 1. 1. 5   
R e c o r di n g  a n d  R e p o rti n g  of  A d v e rs e  E v e nts  
R e c o r di n g  of  A d v e rs e  E v e nts  
All  A Es  of  a n y  p ati e nt  d uri n g t h e  c o urs e  of t h e r es e ar c h st u d y  will  b e r e c or d e d i n t h e  e C R F,  a n d 
t h e i n v esti g at or  will  gi v e  his  or  h er  o pi ni o n  as t o t h e r el ati o ns hi p  of t h e  A E t o t h e st u d y  dr u g 
tr e at m e nt (i. e.,  w h et h er t h e  e v e nt is r el at e d  or  u nr el at e d t o st u d y  dr u g  a d mi nistr ati o n). 
All  A Es s h o ul d  b e  d o c u m e nt e d.   A  d es cri pti o n  of t h e  e v e nt, i n cl u di n g its  d at e  of  o ns et  a n d 
r es ol uti o n,  w h et h er it  c o nstit ut es  an  S A E  or  n ot,  a n y  a cti o n t a k e n ( e. g.,  c h a n g es t o st u d y 
tr e at m e nt),  a n d  o ut c o m e, s h o ul d  b e  pr o vi d e d,  al o n g  wit h t h e i n v esti g at or’s  ass ess m e nt  of 
c a us alit y (i. e., t h e r el ati o ns hi p t o t h e st u d y tr e at m e nt[s]).   F or  a n  A E t o  b e  a s us p e ct e d tr e at m e nt-
r el at e d  e v e nt t h er e s h o ul d  b e  at l e ast  a r e as o n a bl e  p ossi bilit y  of  a  c a us al r el ati o ns hi p  b et w e e n t h e 
pr ot o c ol tr e at m e nt  a n d t h e  A E.   A d v ers e  e v e nts  will  b e  gr a d e d  a c c or di n g t o t h e  N CI  C T C A E 
v 4. 0 3,  a n d  c h a n g es  will  b e  d o c u m e nt e d. 
If t h e  A E is s eri o us, it s h o ul d  b e r e p ort e d i m m e di at el y t o  S C RI I n n o v ati o ns S af et y  D e p art m e nt.  
Ot h er  u nt o w ar d  e v e nts  o c c urri n g i n t h e fr a m e w or k  of  a  cli ni c al st u d y  ar e t o  b e r e c or d e d  as  A Es 
(i. e.,  A Es t h at  o c c ur  pri or t o  assi g n m e nt  of st u d y tr e at m e nt t h at  ar e r el at e d t o  a  pr ot o c ol-
m a n d at e d i nt er v e nti o n, i n cl u di n g i n v asi v e  pr o c e d ur es s u c h  as  bi o psi es,  m e di c ati o n  w as h o ut,  or 
n o tr e at m e nt r u n- i n). 
A n y  cli ni c all y si g nifi c a nt si g ns  a n d s y m pt o ms;  a b n or m al t est fi n di n gs;  c h a n g es i n  p h ysi c al 
e x a mi n ati o n;  h y p ers e nsiti vit y;  a n d  ot h er  m e as ur e m e nts t h at  o c c ur  will  b e r e p ort e d  as  a n  A E,  a n d 
c oll e ct e d  o n t h e r el e v a nt  e C R F s cr e e n.  
T est fi n di n gs  will  b e r e p ort e d  as  a n  A E if: t h e t est r es ult r e q uir es  a n  a dj ust m e nt i n t h e st u d y 
dr u g(s)  or  dis c o nti n u ati o n  of tr e at m e nt,  a n d/  or t est fi n di n gs r e q uir e  a d diti o n al t esti n g  or s ur gi c al 
i nt er v e nti o n,  a t est r es ult  or fi n di n g is  ass o ci at e d  wit h  a c c o m p a n yi n g s y m pt o ms,  or  a t est r es ult is 
c o nsi d er e d t o  b e  a n  A E  b y t h e i n v esti g at or. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 3  of  6 9  
R e p o rti n g  P e ri o d f o r  A d v e rs e  E v e nts  
All  A Es r e g ar dl ess  of s eri o us n ess  or r el ati o ns hi p t o  n a b -p a clit a x el /g e m cit a bi n e  tr e at m e nt ( c all e d 
st u d y tr e at m e nt), s p a n ni n g fr o m t h e st art  of st u d y tr e at m e nt ,  u ntil  3 0  c al e n d ar  d a ys  aft er 
dis c o nti n u ati o n  or  c o m pl eti o n  of st u d y tr e at m e nt  as  d efi n e d  b y t h e  cli ni c al st u d y f or t h at  p ati e nt, 
ar e t o  b e r e c or d e d  o n t h e  c orr es p o n di n g s cr e e n(s) i n cl u d e d i n t h e  e C R F.   
All  A Es r es ulti n g i n  dis c o nti n u ati o n fr o m t h e st u d y s h o ul d  b e f oll o w e d  u ntil r es ol uti o n  or 
st a bili z ati o n.   All  n e w  A Es  o c c urri n g  d uri n g t his  p eri o d  m ust  b e r e p ort e d  a n d f oll o w e d  u ntil 
r es ol uti o n  u nl ess, i n t h e  o pi ni o n  of t h e i n v esti g at or, t h e  A E  or l a b orat or y  a b n or m alit y/i es  ar e  n ot 
li k el y t o i m pr o v e  b e c a us e  of t h e  u n d erl yi n g  dis e as e.  I n t his  c as e, t h e i n v esti g at ors  m ust r e c or d 
his  or  h er r e as o ni n g f or t his  d e cisi o n i n t h e  p ati e nt’s  m e di c al r e c or d  a n d  as  a  c o m m e nt  o n t h e 
e C R F s cr e e n.    
Aft er  3 0  d a ys  of  c o m pl eti o n  of  pr ot o c ol-s p e cifi c tr e at m e nt  or  dis c o nti n u ati o n,  o nl y  A Es,  S A Es, 
or  d e at hs  ass ess e d  b y t h e i n v esti g at or  as tr e at m e nt r el at e d  ar e t o  b e r e p ort e d.  
1 1. 1. 6   
Ass ess m e nt  of  A d v e rs e  E v e nts  
All  A Es  a n d  S A Es  w h et h er  v ol u nt e er e d  b y t h e  p ati e nt,  dis c o v er e d  b y st u d y  p ers o n n el  d uri n g 
q u esti o ni n g,  or  d et e ct e d t hr o u g h  p h ysi c al  e x a mi n ati o n, l a b or at or y t est,  or  ot h er  m e a ns  will  b e 
r e p ort e d  a p pr o pri at el y.   E a c h r e p ort e d  A E  or  S A E  will  b e  d es cri b e d  b y its  d ur ati o n (i. e., st art  a n d 
e n d  d at es), r e g ul at or y s eri o us n ess  crit eri a if  a p pli c a bl e, s us p e ct e d r el ati o ns hi p t o t h e st u d y  dr u g 
(s e e f oll o wi n g  g ui d a n c e),  a n d  a cti o ns t a k e n. 
T o  e ns ur e  c o nsist e n c y  of  A E  a n d  S A E  c a us alit y  ass ess m e nts, i n v esti g at ors s h o ul d  a p pl y t h e 
f oll o wi n g  g e n er al  g ui d eli n e: 
Y E S:   T h er e is  a  pl a usi bl e t e m p or al r el ati o ns hi p  b et w e e n t h e  o ns et  of t h e  A E  a n d 
a d mi nistr ati o n  of t h e st u d y  m e di c ati o n,  a n d t h e  A E  c a n n ot  b e r e a dil y  e x pl ai n e d  b y t h e 
p ati e nt’s  cli ni c al st at e, i nt er c urr e nt ill n ess,  or  c o n c o mit a nt t h er a pi es,  a n d/ or t h e  A E 
f oll o ws  a  k n o w n  p att er n  of r es p o ns e t o t h e st u d y  dr u g,  a n d/ or t h e  A E  a b at es  or r es ol v es 
u p o n  dis c o nti n u ati o n  of t h e st u d y  dr u g  or  d os e r e d u cti o n  a n d, if  a p pli c a bl e, r e a p p e ars 
u p o n r e- c h all e n g e.  
N O:    E vi d e n c e  e xists t h at t h e  A E  h as  a n  eti ol o g y  ot h er t h a n t h e st u d y  dr u g ( e. g.,  pr e-
e xisti n g  m e di c al  c o n diti o n,  u n d erl yi n g  dis e as e, i nt er c urr e nt ill n ess,  or  c o n c o mit a nt 
m e di c ati o n),  a n d/ or t h e  A E  h as  n o  pl a usi bl e t e m p or al r el ati o ns hi p t o st u d y  dr u g 
a d mi nistr ati o n ( e. g.,  c a n c er  di a g n os e d  2  d a ys  aft er first  d os e  of st u d y  dr u g). 
1 1. 2   
S e ri o us  A d v e rs e  E v e nt  R e p o rti n g  b y I n v esti g at o rs 
A d v ers e  e v e nts  cl assifi e d  b y t h e tr e ati n g i n v esti g at or  as s eri o us r e q uir e  e x p e diti o us  h a n dli n g  a n d 
r e p orti n g t o  S C RI I n n o v ati o ns  S af et y  D e p art m e nt i n  or d er t o  c o m pl y  wit h r e g ul at or y 
r e q uir e m e nts.   D et er mi n ati o n  of lif e-t hr e at e ni ng  or s eri o us is  b as e d  o n t h e  o pi ni o n  of  eit h er t h e 
S p o ns or  or t h e I n v esti g at or.   
S eri o us  A Es  m a y  o c c ur  at  a n y ti m e fr o m t h e st art  of st u d y tr e at m e nt  t hr o u g h t h e  3 0  d a y f oll o w-
u p  p eri o d  aft er t h e l ast st u d y tr e at m e nt.   T h e  S C RI  I n n o v ati o ns S af et y  D e p a rt m e n t  m ust  b e 
n otifi e d  of  all  S A Es,  r e g a r dl ess  of  c a us alit y,  wit hi n  2 4  h o u rs  of t h e fi rst  k n o wl e d g e  of t h e 
e v e nt  b y t h e t r e ati n g  p h ysi ci a n  o r  r es e a r c h  p e rs o n n el.    


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 4  of  6 9  
T o r e p ort  a  S A E, t h e  S A E  R e p ort  F or m s h o ul d  b e  c o m pl et e d  wit h t h e  n e c ess ar y i nf or m ati o n. 
T h e  S A E  r e p ort s h o ul d  b e s e nt t o  S C RI I n n o v ati o ns S af et y  D e p art m e nt  vi a f a x  or  e -m ail  usi n g 
t h e  usi n g t h e f oll o wi n g  c o nt a ct i nf or m ati o n ( d uri n g  b ot h  b usi n ess  a n d  n o n- b usi n ess  h o urs): 
S C RI  I n n o v ati o ns S af et y  D e p art m e nt  
S af et y  D e pt.  P h o n e  #:   1- 6 1 5- 3 2 9- 7 3 5 8 
S af et y  D e pt.  F a x  #:       1- 8 6 6- 8 0 7- 4 3 2 5 
S af et y  D e pt.  E m ail:      C A N N. S A E @s cri -i n n o v ati o ns. c o m 
Tr a ns missi o n  of t h e  S A E r e p ort s h o ul d  b e  c o nfir m e d  b y t h e sit e  p ers o n n el s u b mitti n g t h e r e p ort. 
F oll o w- u p i nf or m ati o n f or  S A Es  a n d i nf or m ati o n  o n  n o n-s eri o us  A Es t h at  b e c o m e s eri o us s h o ul d 
als o  b e r e p ort e d t o  S C RI I n n o v ati o ns  S af et y  D e p art m e nt  as s o o n  as it is  a v ail a bl e; t h es e r e p orts 
s h o ul d  b e s u b mitt e d  usi n g t h e  S C RI I n n o v ati o ns  S A E  R e p ort  F or m. 
I n v esti g at ors  m ust r e p ort  S A Es  a n d f oll o w- u p i nf or m ati o n t o t h eir r es p o nsi bl e I R B  a c c or di n g t o 
t h e  p oli ci es  of t h e r es p o nsi bl e I R B. 
1 1. 3   
R e c o r di n g  of  A d v e rs e  E v e nts  a n d  S e ri o us  A d v e rs e  E v e nts  
1 1. 3. 1   
Di a g n osis  v e rs us  Si g ns  a n d  S y m pt o ms 
All  A Es s h o ul d  b e r e c or d e d i n di vi d u all y i n t h e  p ati e nt’s  o w n  w or ds ( v er b ati m)  u nl ess, i n t h e 
o pi ni o n  of t h e I n v esti g at or  or  d esi g n at e d  p h ysi ci a n, t h e  A Es  c o nstit ut e  c o m p o n e nts  of  a 
r e c o g ni z e d  c o n diti o n,  dis e as e,  or s y n dr o m e.  I n t h e l att er  c as e, t h e  c o n diti o n,  dis e as e,  or 
s y n dr o m e s h o ul d  b e  n a m e d r at h er t h a n  e a c h i n di vi d u al si g n  or s y m pt o m.  If  a  c o nst ell ati o n  o f 
si g ns  a n d/ or s y m pt o ms  c a n n ot  b e  m e di c all y  c h ar a ct eri z e d  as  a si n gl e  di a g n osis  or s y n dr o m e  at 
t h e ti m e  of r e p orti n g,  e a c h i n di vi d u al  e v e nt s h o ul d  b e r e c or d e d  as  a n  A E  or  S A E  as  a p pr o pri at e 
o n t h e r el e v a nt f or m(s) ( S A E  R e p ort  F or m  a n d/ or  A E  e C R F s cr e e n).   If  a  di a g n osis is 
s u bs e q u e ntl y  est a blis h e d, it s h o ul d  b e r e p ort e d  as f oll o w- u p i nf or m ati o n is  a v ail a bl e.  If  a 
di a g n osis is  d et er mi n e d s u bs e q u e nt t o t h e r e p orti n g  of t h e  c o nst ell ati o n  of s y m pt o ms, t h e 
si g ns/s y m pt o ms s h o ul d  b e  u p d at e d t o r efl e ct t h e  di a g n os is. 
Pr o gr essi o n  of  m ali g n a n c y (i n cl u di n g f at al  o ut c o m es), if  d o c u m e nt e d  b y  us e  of  a p pr o pri at e 
m et h o d (f or  e x a m pl e,  as  p er  R E CI S T  crit eri a f or s oli d t u m ors), s h o ul d  n ot  b e r e p ort e d  as  a n 
S A E.  
1 1. 3. 2   
P e rsist e nt  o r  R e c u r r e nt  A d v e rs e  E v e nts  
A  p ersist e nt  A E is  o n e t h a t  e xt e n ds  c o nti n u o usl y,  wit h o ut r es ol uti o n,  b et w e e n  p ati e nt  e v al u ati o n 
ti m e  p oi nts.   S u c h  e v e nts s h o ul d  o nl y  b e r e c or d e d  o n c e  o n t h e  S A E  R e p ort  F or m  a n d/ or t h e  A E 
e C R F s cr e e n.  If  a  p ersist e nt  A E  b e c o m es  m or e s e v er e  or l ess e ns i n s e v erit y, it s h o ul d  b e 
r e c or d e d  o n  a s e p ar at e  S A E  R e p ort  F or m  a n d/ or  A E  e C R F s cr e e n. 
A r e c urr e nt  A E is  o n e t h at  o c c urs  a n d r es ol v es  b et w e e n  p ati e nt  e v al u ati o n ti m e  p oi nts,  a n d 
s u bs e q u e ntl y r e c urs.   All r e c urr e nt  A Es s h o ul d  b e r e c or d e d  o n  a n  S A E  R e p ort  F or m  a n d/ or  A E 
e C R F s cr e e n.  
1 1. 3. 3   
A b n o r m al  L a b o r at o r y  V al u es 
If  a n  a b n or m al l a b or at or y  v al u e  or  vit al si g n is  ass o ci at e d  wit h  cli ni c al si g ns  a n d/ or s y m pt o ms, 
t h e si g n  or s y m pt o m s h o ul d  b e r e p ort e d  as  a n  A E  or  S A E,  a n d t h e  ass o ci at e d l a b or at or y  v al u e  or 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 5  of  6 9  
vit al si g n s h o ul d  b e  c o nsi d er e d  a d diti o n al i nf or m ati o n t h at  m ust  b e  c oll e ct e d  o n t h e r el e v a nt 
e C R F s cr e e n.  If t h e l a b or at or y  a b n or m alit y is  a si g n  of  a  dis e as e  or s y n dr o m e,  o nl y t h e  di a g n osis 
n e e ds t o  b e r e c or d e d  o n t h e  S A E  R e p ort  F or m  or  A E  e C R F s cr e e n. 
A b n or m al l a b or at or y  v al u es  will  b e r e p o rt e d  as  a n  A E if: t h e l a b or at or y r es ult r e q uir es  a n 
a dj ust m e nt i n t h e st u d y  dr u g(s)  or  dis c o nti n u ati o n  of tr e at m e nt,  a n d/  or l a b or at or y fi n di n gs 
r e q uir e  a d diti o n al t esti n g  or s ur gi c al i nt er v e nti o n,  a l a b or at or y r es ult  or fi n di n g is  ass o ci at e d  wit h 
a c c o m p a n yi n g s y m pt o ms,  or  a l a b or at or y r es ult is  c o nsi d er e d t o  b e  a n  A E  b y t h e i n v esti g at or. 
1 1. 3. 4   
D e at hs  
D e at hs t h at  o c c ur  d uri n g t h e  pr ot o c ol-s p e cifi e d  A E r e p orti n g  p eri o d t h at  ar e  attri b ut e d  b y t h e 
I n v esti g at or s ol el y t o  pr o gr essi o n  of  dis e as e  will  b e r e c or d e d  o n t h e “ St u d y  Dis c o nti n u ati o n ” 
e C R F s cr e e n.   All  ot h er  o n st u d y  d e at hs, r e g ar dl ess  of  attri b uti o n,  will  b e r e c or d e d  o n  a n  S A E 
R e p ort  F or m  a n d  e x p e diti o usl y r e p ort e d t o t h e  S C RI I n n o v ati o ns  S af et y  D e p art m e nt.  
W h e n r e c or di n g  a  S A E  wit h  a n  o ut c o m e  of  d e at h, t h e  e v e nt  or  c o n diti o n t h at  c a us e d  or 
c o ntri b ut e d t o t h e f at al  o ut c o m e s h o ul d  b e r e c or d e d  as t h e si n gl e  m e di c al  c o n c e pt  o n t h e  S A E 
R e p ort  F or m  a n d  A d v ers e  E v e nt s cr e e n  of t h e  e C R F.  If t h e  c a us e  of  d e at h is  u n k n o w n  a n d 
c a n n ot  b e  as c ert ai n e d  at t h e ti m e  of r e p orti n g, r e c or d  “ D e at h  N O S ”  o n t h e  e C R F  A d v ers e  E v e nt 
s cr e e n.   D uri n g  p ost-st u d y s ur vi v al f oll o w- u p,  d e at hs  attri b ut e d t o  pr o gr essi o n  of  dis e as e  will  b e 
r e c or d e d  o nl y  o n t h e  “ Aft er  Pr o gr essi v e  Dis e as e  F oll o w-U p ”  e C R F s cr e e n.  
1 1. 3. 5   
H os pit ali z ati o n,  P r ol o n g e d  H os pit ali z ati o n,  o r  S u r g e r y  
A n y  A E t h at r es ults i n  h os pit ali z ati o n  of  ≥ 2 4  h o urs  or  pr ol o n g ati o n  of  pr e- e xisti n g 
h os pit ali z ati o n s h o ul d  b e  d o c u m e nt e d  a n d r e p ort e d  as  a n  S A E  u nl ess s p e cifi c all y i nstr u ct e d 
ot h er wis e i n t his  pr ot o c ol.   T h er e  ar e s o m e  h os pit ali z ati o ns t h at  d o  n ot r e q uir e r e p orti n g  as  a n 
S A E.  
Tr e at m e nt  wit hi n  or  a d missi o n t o t h e f oll o wi n g f a ciliti es is  n ot  c o nsi d er e d t o  m e et t h e  crit eri a  of 
“i n p ati e nt  h os pit ali z ati o n ” ( alt h o u g h if  a n y  ot h er  S A E  crit eri a  ar e  m et, t h e  e v e nt  m ust still  b e 
tr e at e d  as  a n  S A E  a n d i m m e di at el y r e p ort e d): 
•   E m er g e n c y  D e p art m e nt  or  E m er g e n c y  R o o m 
•   O ut p ati e nt  or s a m e - d a y s ur g er y  u nits 
•   O bs er v ati o n  or s h ort-st a y  u nit 
•   R e h a bilit ati o n f a cilit y  
•   H os pi c e  or s kill e d  n ursi n g f a cilit y  
•   N ursi n g  h o m es,  C ust o di al  c ar e  or  R es pit e  c ar e f a cilit y  
H os pit ali z ati o n  d uri n g t h e st u d y f or  a  pr e- pl a n n e d s ur gi c al  or  m e di c al  pr o c e d ur e ( o n e  w hi c h  w as 
pl a n n e d  pri or t o  e ntr y i n t h e st u d y),  d o es  n ot r e q uir e r e p orti n g  as  a n  S A E t o t h e  S C RI  
I n n o v ati o ns S af et y  D e p art m e nt.  
1 1. 3. 6   
P r e -E xisti n g  M e di c al  C o n diti o ns  
A  pr e -e xisti n g  m e di c al  c o n diti o n is  o n e t h at is  pr es e nt  at t h e st art  of t h e st u d y.   S u c h  c o n diti o ns 
s h o ul d  b e r e c or d e d  o n t h e  G e n er al  M e di c al  Hist or y  e C R F s cr e e n.   A  pr e- e xisti n g  m e di c al 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 6  of  6 9  
c o n diti o n s h o ul d  b e r e c or d e d  as  a n  A E  or  S A E  o nl y if t h e fr e q u e n c y, s e v erit y,  or  c h ar a ct er  of t h e 
c o n diti o n  w ors e ns  d uri n g t h e st u d y.   W h e n r e c or di n g s u c h  e v e nts  o n  a n  S A E  R e p ort  F or m  a n d/ or 
A E   e C R F s cr e e n, it is i m p ort a nt t o  c o n v e y t h e  c o n c e pt t h at t h e  pr e- e xisti n g  c o n diti o n  h as 
c h a n g e d  b y i n cl u di n g  a p pli c a bl e  d es cri pt ors. 
1 1. 3. 7   
N e w  C a n c e rs  
T h e  d e v el o p m e nt  of  a  n e w  pri m ar y  c a n c er s h o ul d  b e r e g ar d e d  as  a n  A E  a n d  will  g e n er all y  m e et 
at l e ast  o n e  of t h e s eri o us n ess  crit eri a (s e e  S e cti o n  1 1. 2 ).   N e w  pri m ar y  c a n c ers  ar e t h os e t h at  ar e 
n ot t h e  pri m ar y r e as o n f or t h e  a d mi nistr ati o n  of t h e st u d y tr e at m e nt  a n d  h a v e  d e v el o p e d  aft er t h e 
i ncl usi o n  of t h e  p ati e nt i nt o t h e st u d y.   T h e y  d o  n ot i n cl u d e  m et ast as es  of t h e  ori gi n al  c a n c er.  
S y m pt o ms  of  m et ast asis  or t h e  m et ast asis its elf  s h o ul d  n ot  b e r e p ort e d  as  a n  A E/ S A E,  as t h e y  ar e 
c o nsi d er e d t o  b e  dis e as e  pr o gr essi o n. 
1 1. 3. 8   
P r e g n a n c y,  A b o rti o n,  Bi rt h  D ef e cts/ C o n g e nit al  A n o m ali es  
If  a  p ati e nt  b e c o m es  pr e g n a nt  w hil e  e nr oll e d i n t h e st u d y,  or  wit hi n  3  m o nt hs  of t h e l ast  d os e  of 
n a b -p a clit a x el  or  g e m cit a bi n e ,  a  Pr e g n a n c y  F or m s h o ul d  b e  c o m pl et e d  a n d f a x e d t o t h e  S C RI 
I n n o v ati o ns S af et y  D e p art m e nt.   S C RI  I n n o v ati o ns S af et y  D e p art m e nt  (S C RI I n n o v ati o ns  S D)  
s h o ul d  b e  n otifi e d  e x p e diti o usl y, irr es p e cti v e  of  w h et h er  or  n ot it  m e ets t h e  crit eri a f or  e x p e dit e d 
r e p orti n g.   A b orti o ns (s p o nt a n e o us,  a c ci d e nt al,  or t h er a p e uti c)  m ust  als o  b e r e p ort e d t o  S C RI 
I n n o v ati o ns S af et y  D e p art m e nt.  
N a b -p a clit a x el  a n d  g e m cit a bi n e  ar e  t o  b e  dis c o nti n u e d i m m e di at el y if  a  p ati e nt  b e c o m es 
pr e g n a nt  w hil e  o n st u d y.   T h e   pr e g n a n c y, s us p e ct e d  pr e g n a n c y,  or  p ositi v e  pr e g n a n c y t est  m ust 
b e r e p ort e d t o  S C RI I n n o v ati o ns  S D  i m m e di at el y  b y f a csi mil e,  or  ot h er  a p pr o pri at e  m et h o d, 
usi n g t h e  Pr e g n a n c y I niti al  R e p ort  F or m,  or  a p pr o v e d  e q ui v al e nt f or m.   T h e f e m al e s u bj e ct  m a y 
b e r ef err e d t o  a n  o bst etri ci a n - g y n e c ol o gist ( n ot  n e c ess aril y  o n e  wit h r e pr o d u cti v e t o xi cit y 
e x p eri e n c e)  or  a n ot h er  a p pr o pri at e  h e alt h c ar e  pr of essi o n al f or f urt h er  e v al u ati o n.   
T h e I n v esti g at or  will f oll o w t h e f e m al e s u bj e ct  u ntil  c o m pl eti o n  of t h e  pr e g n a n c y,  a n d  m ust 
n otif y  C el g e n e  Dr u g  S af et y i m m e di at el y  a b o ut t h e  o ut c o m e  of t h e  pr e g n a n c y ( eit h er  n or m al  or 
a b n or m al  o ut c o m e)  usi n g t h e  Pr e g n a n c y  F oll o w- u p  R e p ort  F or m,  or  a p pr o v e d  e q ui v al e nt f or m.  
If t h e  o ut c o m e  of t h e  pr e g n a n c y  w as  a b n or m al ( e. g., s p o nt a n e o us  or t h er a p e uti c  a b orti o n), t h e 
I n v esti g at or s h o ul d r e p ort t h e  a b n or m al  o ut c o m e  as  a n  A E.  If t h e  a b n or m al  o ut c o m e  m e ets  a n y 
of t h e s eri o us  crit eri a, it  m ust  b e r e p ort e d  as  a n  S A E t o  C el g e n e  Dr u g  S af et y i m m e di at el y  b y 
f a csi mil e,  or  ot h er  a p pr o pri at e  m et h o d,  wit hi n  2 4  h o urs  of t h e I n v esti g at or’s  k n o wl e d g e  of t h e 
e v e nt  usi n g t h e  S A E  R e p ort  F or m,  or  a p pr o v e d  e q ui v al e nt f or m. 
All  n e o n at al  d e at hs t h at  o c c ur  wit hi n  2 8  d a ys  of  birt h s h o ul d  b e r e p ort e d,  wit h o ut r e g ar d t o 
c a us alit y,  as  S A Es.   I n  a d diti o n,  a n y i nf a nt  d e at h  aft er  2 8  d a ys t h at t h e I n v esti g at or s us p e cts is 
r el at e d t o t h e i n  ut er o  e x p os ur e t o t h e st u d y  dr u gs  s h o ul d  als o  b e r ep ort e d t o  C el g e n e  Dr u g 
S af et y i m m e di at el y  b y f a csi mil e,  or  ot h er  a p pr o pri at e  m et h o d,  wit hi n  2 4  h o urs  of t h e 
I n v esti g at or’s  k n o wl e d g e  of t h e  e v e nt  usi n g t h e  S A E  R e p ort  F or m,  or  a p pr o v e d  e q ui v al e nt f or m.  
If  a f e m al e  p art n er  of  a  m al e  p ati e nt  b e c o m es  pr e g n a nt  d uri n g t h e  m al e  p ati e nt’s  p arti ci p ati o n i n 
t his st u d y,  d uri n g tr e at m e nt  or f or  6  m o nt hs  aft er st o p pi n g tr e at m e nt, t h e  m al e s u bj e ct t a ki n g 
st u d y  dr u gs s h o ul d  n otif y t h e st u d y  d o ct or.   T his  pr e g n a n c y  m ust  b e r e p ort e d t o t h e  S C RI 
I n n o v ati o ns S af et y  D e p art m e nt  a n d  t h e y  will i nf or m C el g e n e  i m m e di at el y.  T h e  pr e g n a nt f e m al e 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 7  of  6 9  
p art n er s h o ul d  b e  a d vis e d t o  c all t h eir  h e alt h c ar e  pr o vi d er i m m e di at el y.   E v er y   eff ort s h o ul d  b e 
m a d e t o f oll o w t h e  pr e g n a n c y f or t h e fi n al  pr e g n a n c y  o ut c o m e. 
C o n g e nit al  a n o m ali es/ birt h  d ef e cts  al w a ys  m e et  S A E  crit eri a,  a n d s h o ul d t h er ef or e  b e 
e x p e diti o usl y r e p ort e d  as  a n  S A E,  usi n g t h e  pr e vi o usl y  d es cri b e d  pr o c ess f or  S A E r e p orti n g.   A 
Pr e g n a n c y  F or m s h o ul d  als o  h a v e  b e e n  pr e vi o usl y  c o m pl et e d,  a n d  will  n e e d t o  b e  u p d at e d t o 
r efl e ct t h e  o ut c o m e  of t h e  pr e g n a n c y. 
1 1. 3. 9   
O v e r d os e   of  N a b- p a clit a x el  of  G e m cit a bi n e 
S y m pt o m ati c  a n d  n o n-s y m pt o m ati c  o v er d os e  m ust  b e r e p ort e d i n t h e  e C R F.   A n y  a c ci d e nt al  or 
i nt e nti o n al  o v er d os e  wit h eit h er  n a b -p a clit a x el  or  g e m cit a bi n e  t h at is s y m pt o m ati c,  e v e n if  n ot 
f ulfilli n g  a s eri o us n ess  crit eri o n, is t o  b e r e p ort e d t o t h e  S C RI I n n o v ati o ns S af et y  D e p art m e nt  n o 
gr e at er t h a n  2 4  h o urs fr o m first  k n o wl e d g e  of t h e  e v e nt  usi n g t h e  c orr es p o n di n g s cr e e ns i n t h e 
e C R F  a n d f oll o wi n g t h e s a m e  pr o c ess  d es cri b e d f o r  S A E r e p orti n g (s e e S e cti o n  1 1. 2 ) if t h e 
o v er d os e is s y m pt o m ati c. 
F or i nf or m ati o n  o n  h o w t o  m a n a g e  a n  o v er d os e  of  n a b -p a clit a x el  or  g e m cit a bi n e , s e e t h e 
a p pr o pri at e ( n a b -p a clit a x el)  I n v esti g at or’s  Br o c h ur e  or f oll o w st a n d ar d  g ui d eli n es. 
1 1. 4   
S p o ns o r  S e ri o us  A d v e rs e  E v e nt  R e p o rti n g  R e q ui r e m e nts  
S C RI  I n n o v ati o ns S af et y  D e p art m e nt  will f or w ar d  S A E i nf or m ati o n  ( usi n g  S C RI  S D  S A E f or m) 
t o C el g e n e  wit hi n  1  b usi n ess  d a y  of  S C RI I n n o v ati o ns  S af et y  D e p art m e nt  p ers o n n el  b e c o mi n g 
a w ar e  of t h e  S A E.   T h e  writt e n r e p ort  m ust  b e  c o m pl et e d  a n d s u p pli e d t o  C el g e n e  b y f a csi mil e 
wit hi n  1  b usi n ess  d a y.   T h e i niti al r e p ort  m ust  b e  as  c o m pl et e  as  p ossi bl e, i n cl u di n g  a n 
ass ess m e nt  of t h e  c a us al r el ati o ns hi p  b et w e e n t h e  e v e nt  a n d t h e i n v esti g ati o n al  pr o d u ct(s), if 
a v ail a bl e.  I nf or m ati o n  n ot  a v ail a bl e  at t h e ti m e  of t h e i niti al r e p ort ( e. g.,  a n  e n d  d at e f or t h e  A E  
or l a b or at or y  v al u es r e c ei v e d  aft er t h e r e p ort)  m ust  b e  d o c u m e nt e d  o n  a f oll o w- u p r e p ort.   A 
fi n al r e p ort t o  d o c u m e nt r es ol uti o n  of t h e  S A E is r e q uir e d.   T h e  C el g e n e  C or p or ati o n st u d y 
n u m b er  a n d t h e  S C RI  st u d y  n u m b er s h o ul d  b e i n cl u d e d  o n  S A E r e p orts ( or  o n t h e f a x  c o v er 
l ett er) s e nt t o  C el g e n e.   A  c o p y  of t h e f a x tr a ns missi o n  c o nfir m ati o n  of t h e  S A E r e p ort t o 
C el g e n e s h o ul d  b e  att a c h e d t o t h e  S A E  a n d r et ai n e d  wit h t h e  p ati e nt r e c or ds.  
S af et y  R e p o rti n g t o  C el g e n e  C o r p o r ati o n : 
S af et y r e p orti n g  will  b e  c o m m u ni c at e d t o  C el g e n e  C or p or ati o n  usi n g t h e  c o nt a ct i nf or m ati o n 
b el o w: 
C el g e n e  C o r p o r ati o n  
Gl o b al  Dr u g  S af et y  a n d  Ris k  M a n a g e m e nt  
C o n n ell  C or p or at e  P ar k 
3 0 0  C o n n ell  Dr.   S uit e  6 0 0 0 
B er k el e y  H ei g hts,  NJ   0 7 9 2 2 
F a x: ( 9 0 8)  6 7 3- 9 1 1 5 
E- m ail:  dr u gs af et y @ c el g e n e. c o m  
C el g e n e  C or p or ati o n  St u d y  n u m b er:  A X- C L -B L D -PI - 0 0 4 9 9 3 
S C RI  St u d y  n u m b er:   G U  1 2 4 
S C RI I n n o v ati o ns is r es p o nsi bl e f or r e p orti n g r el e v a nt  S A Es t o t h e  c o m p et e nt  a ut h orit y,  ot h er 
a p pli c a bl e r e g ul at or y  a ut h oriti es,  a n d  p arti ci p ati n g i n v esti g at ors, i n  a c c or d a n c e  wit h I nt er n ati o n al 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 8  of  6 9  
C o nf er e n c e  o n  H ar m o nis ati o n ( I C H)  g ui d eli n es,  F D A r e g ul ati o ns,  a n d/ or l o c al r e g ul at or y 
r e q uir e m e nts. 
1 1. 4. 1   
S p o ns o r  Ass ess m e nt  of  U n e x p e ct e d  
T h e  S C RI I n n o v ati o ns is r es p o nsi bl e f or  ass essi n g  a n  A E  or s us p e ct e d  a d v ers e  e v e nt  as   
“ u n e x p e ct e d . ” 
A n  A E  or s us p e ct e d  a d v ers e r e a cti o n  ( S A R) is  c o nsi d er e d  “ u n e x p e ct e d ”  w h e n t h e f oll o wi n g 
c o n diti o ns  o c c ur: 
•   E v e nt(s) is  n ot  m e nti o n e d i n t h e I n v esti g at or’s  Br o c h ur e ( I B) ( or  c urr e nt U S PI ) 
•   E v e nt(s) is  n ot list e d  at t h e s p e cifi cit y  or s e v erit y t h at  h as  b e e n  o bs er v e d 
•   A n  e v e nt(s) is  n ot  c o nsist e nt  wit h t h e  G e n er al I n v esti g ati v e  Pl a n  or i n t h e  c urr e nt 
a p pli c ati o n  
•   I n cl u d es  A Es  or  S A R t h at  m a y  b e  a nti ci p at e d fr o m t h e  p h ar m a c ol o gi c al  pr o p erti es  of t h e 
st u d y  dr u g,  or t h at  o c c ur  wit h  m e m b ers  of t h e  dr u g  cl ass,  b ut t h at  h a v e  pr e vi o usl y  b e e n 
o bs er v e d  u n d er i n v esti g ati o n 
W h e n  a p pli c a bl e,  a n  u n e x p e ct e d  A E  m a y  als o  a p pl y t o  a n  e v e nt t h at is  n ot list e d i n t h e  c urr e nt 
U S PI  or  a n  e v e nt t h at  m a y  b e  m e nti o n e d i n t h e  U S PI,  b ut  diff ers fr o m t h e  e v e nt  b e c a us e  of 
gr e at er s e v erit y  or s p e cifi cit y.     
K n o w n  as  S us p e ct e d  U n e x p e ct e d  S eri o us  A d v ers e  R e a cti o ns ( S U S A R), t h es e  e v e nts s us p e ct e d 
( b y t h e I n v esti g at or  or  S p o ns or) t o  b e r el at e d t o t h e st u d y  dr u g,  ar e  u n e x p e ct e d ( n ot list e d i n t h e 
I B  or  U S PI),  a n d  ar e s eri o us ( as  d efi n e d  b y t h e  pr ot o c ol)  a n d r e q uir e  e x p e di e nt s u b missi o n t o 
r el e v a nt  h e alt h  a ut h oriti es  wit hi n  7  d a ys (f at al  or lif e-t hr e at e ni n g  e v e nt)  or  1 5  d a ys ( all s eri o us 
e v e nts),  or  as  d efi n e d  b y l a w.   T h e t er m  S U S A R is  us e d  pri m aril y i n t h e r e p orti n g  of  e v e nts t o 
r e g ul at or y  a ut h oriti es. 
E x p e ct e d  A Es  ar e t h os e  e v e nts t h at  ar e list e d  or  c h ar a ct eri z e d i n t h e  P a c k a g e I ns ert  or  c urr e nt I B.  
1 1. 4. 2   
S p o ns o r  R e p o rti n g f o r  Cli ni c al  St u di es  U n d e r  a n I n v esti g ati o n a l  N e w  D r u g 
A p pli c ati o n  
All  writt e n I N D  S af et y  R e p orts s u b mitt e d t o t h e  F D A  b y t h e  S C RI  I n n o v ati o ns S af et y 
D e p art m e nt  m ust  als o  b e f a x e d t o  C el g e n e : 
C el g e n e  C o r p o r ati o n  
Att n:  M e di c al  Aff airs  O p er ati o ns  
C o n n ell  C or p or at e  P ar k 
4 0 0  C o n n ell  Dri v e  S uit e  7 0 0 
B er k el e y  H ei g hts,  NJ    0 7 9 2 2 
1 2.   
E T HI C A L,  FI N A N CI A L,  A N D  R E G U L A T O R Y  C O N SI D E R A TI O N S  
T his r es e ar c h  st u d y  will  b e  c o n d u ct e d  a c c or di n g t o t h e st a n d ar ds  of  G o o d  Cli ni c al  Pr a cti c e 
o utli n e d i n t h e I C H  E 6  Tri p artit e  G ui d eli n e  a n d  C F R  Titl e  2 1  p art  3 1 2,  a p pli c a bl e  g o v er n m e n t 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  4 9  of  6 9  
r e g ul ati o ns, i nstit uti o n al r es e ar c h  p oli ci es  a n d  pr o c e d ur es  a n d  a n y  ot h er l o c al  a p pli c a bl e 
r e g ul at or y r e q uir e m e nt(s). 
1 2. 1   
I nstit uti o n al  R e vi e w  B o a r d  A p p r o v al 
T h e  cli ni c al  st u d y pr ot o c ol, i nf or m e d  c o ns e nt f or m ( I C F), I B,  a v ail a bl e s af et y i nf or m ati o n, 
p ati e nt  d o c u m e nts ( e. g., st u d y  di ar y),  p ati e nt r e cr uit m e nt  pr o c e d ur es ( e. g.,  a d v ertis e m e nts), 
i nf or m ati o n  a b o ut  p a y m e nts (i. e.,  Pri n ci p al I n v esti g at or  p a y m e nts)  a n d  c o m p e ns ati o n  a v ail a bl e 
t o t h e  p ati e nts  a n d  d o c u m e nt ati o n  e vi d e n ci n g t h e  Pri n ci p al I n v esti g at or’s  q ualifi c ati o ns  s h o ul d 
b e s u b mitt e d t o t h e I R B f or  et hi c al r e vi e w  a n d  a p pr o v al if r e q uir e d  b y l o c al r e g ul ati o ns,  pri or t o 
t h e st u d y st art. 
T h e  Pri n ci p al I n v esti g at or/ S p o ns or  a n d/ or  d esi g n e e  will f oll o w  all  n e c ess ar y r e g ul ati o ns t o 
e ns ur e  a p pr o pri at e, i niti al,  a n d  o n- g oi n g , I R B st u d y r e vi e w.   T h e  Pri n ci p al I n v esti g at or/ S p o ns or 
( as  a p pr o pri at e)  m ust s u b mit  a n d,  w h er e  n e c ess ar y,  o bt ai n  a p pr o v al fr o m t h e I R B f or  all 
s u bs e q u e nt  pr ot o c ol  a m e n d m e nts  a n d  c h a n g es t o t h e i nf or m e d  c o ns e nt  d o c u m e nt.  I n v esti g at ors 
will  b e   a d vis e d  b y t h e  S p o ns or  or  d esi g n e e  w h et h er  a n  a m e n d m e nt is  c o nsi d er e d s u bst a nti al  or 
n o n-s u bst a nti al  a n d  w h et h er it r e q uir es s u b missi o n f or  a p pr o v al  or  n otifi c ati o n  o nl y t o  a n I R B. 
S af et y  u p d at es f or  n a b -p a clit a x el ,  will  b e  pr e p ar e d  b y t h e  S p o ns or  or its r e pr es e nt ati v e  as 
r e q uir e d, f or distri b uti o n t o t h e I n v esti g at or(s)  a n d  s u b missi o n t o t h e r el e v a nt I R B. 
1 2. 2   
R e g ul at o r y  A p p r o v al 
As r e q uir e d  b y l o c al r e g ul ati o ns, t h e  S p o ns or  will  e ns ur e  all l e g al  as p e cts  ar e  c o v er e d,  a n d 
a p pr o v al  of t h e  a p pr o pri at e r e g ul at or y  b o di es  o bt ai n e d,  pri or t o st u d y i niti ati o n.  If r e q uir e d, t h e 
S p o ns or  will  als o  e ns ur e t h at t h e i m pl e m e nt ati o n  of s u bst a nti al  a m e n d m e nt s t o t h e  pr ot o c ol  a n d 
ot h er r el e v a nt  st u d y  d o c u m e nts  h a p p e n  o nl y  aft er  a p pr o v al  b y t h e r el e v a nt r e g ul at or y  a ut h oriti es. 
1 2. 3   
Inf o r m e d  C o ns e nt  
I nf or m e d  c o ns e nt is  a  pr o c ess  b y  w hi c h  a  p ati e nt  v ol u nt aril y  c o nfir ms  his  or  h er  willi n g n ess t o 
p arti ci p at e i n  a  p arti c ul ar  st u d y aft er  h a vi n g  b e e n i nf or m e d  of  all  as p e cts  of t h e  st u d y t h at  ar e 
r el e v a nt t o t h e  p ati e nt's  d e cisi o n t o  p arti ci pat e.  I nf or m e d  c o ns e nt is  d o c u m e nt e d  b y  m e a ns  of  a 
writt e n, si g n e d,  a n d  d at e d  I C F. 
T h e  I C F will  b e s u b mitt e d f or  a p pr o v al t o t h e I R B t h at is r es p o nsi bl e f or r e vi e w  a n d  a p pr o v al  of 
t h e st u d y.   E a c h  c o ns e nt f or m  m ust i n cl u d e  all  of t h e r el e v a nt  el e m e nts  c urre ntl y r e q uir e d  b y t h e 
F D A,  as  w ell  as l o c al  c o u nt y  a ut h orit y  or st at e r e g ul ati o ns  a n d  n ati o n al r e q uir e m e nts. 
B ef or e r e cr uit m e nt  a n d  e nr oll m e nt i nt o t h e  st u d y,  e a c h  pr os p e cti v e  c a n di d at e  will  b e  gi v e n  a f ull 
e x pl a n ati o n  of t h e r es e ar c h  st u d y.   O n c e t h e  ess enti al i nf or m ati o n  h as  b e e n  pr o vi d e d t o t h e 
pr os p e cti v e  c a n di d at e,  a n d t h e I n v esti g at or is s ur e t h at t h e i n di vi d u al  c a n di d at e  u n d erst a n ds t h e 
i m pli c ati o ns  of  p arti ci p ati n g i n t his r es e ar c h st u d y, t h e  c a n di d at e  will  b e  as k e d t o  gi v e  c o ns e nt t o 
p arti ci p at e i n  t h e st u d y b y si g ni n g  a n  I C F.   A  n ot ati o n t h at  writt e n i nf or m e d  c o ns e nt  h as  b e e n 
o bt ai n e d  will  b e  m a d e i n t h e  p ati e nt’s  m e di c al r e c or d.   A  c o p y  of t h e  I C F, t o i n cl u d e t h e  p ati e nt’s 
si g n at ur e,  will  b e  pr o vi d e d  b y t h e i n v esti g at or t o t h e  p ati e nt. 
If  a n  a m e n dm e nt t o t h e  pr ot o c ol s u bst a nti all y  alt ers t h e  st u d y  d esi g n  or t h e  p ot e nti al ris ks t o t h e 
p ati e nts, t h e  p ati e nt’s  c o ns e nt t o  c o nti n u e  p arti ci p ati o n i n t h e st u d y s h o ul d  b e  o bt ai n e d. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 0  of  6 9  
1 2. 3. 1   
C o nfi d e nti alit y  
1 2. 3. 1. 1   P ati e nt  C o nfi d e nti alit y  
C o nfi d e nti alit y  of  p ati e nt’s  p ers o n a l  d at a  will  b e  pr ot e ct e d i n  a c c or d a n c e  wit h t h e  H e alt h 
I ns ur a n c e  P ort a bilit y  a n d  A c c o u nt a bilit y  A ct  of  1 9 9 6 ( HI P A A).   HI P A A r e g ul ati o ns r e q uir e t h at, 
i n  or d er t o  p arti ci p at e i n t h e st u d y,  a  p ati e nt  m ust si g n  a n  a ut h ori z ati o n f or m f or t h e st u d y t h at  h e 
or s h e  h as  b e e n i nf or m e d  of f oll o wi n g: 
•   W h at  pr ot e ct e d  h e alt h i nf or m ati o n ( P HI)  will  b e  c oll e ct e d fr o m  p ati e nts i n t his  st u d y 
•   W h o  will  h a v e  a c c ess t o t h at i nf or m ati o n  a n d  w h y 
•   W h o  will  us e  or  dis cl os e t h at i nf or m ati o n  
•   T h at  h e alt h i nf or m ati o n  m a y  b e f urt h er  dis cl os e d  b y t h e r e ci pi e nts  of t h e i nf or m ati o n,  a n d 
t h at if t h e i nf or m ati o n is  dis cl os e d t h e i nf or m ati o n  m a y  n o l o n g er  b e  pr ot e ct e d  b y f e d er al 
or st at e  pri v a c y l a ws  
•   T h e i nf or m ati o n  c oll e ct e d  a b o ut t h e r es e ar c h st u d y  will  b e  k e pt s e p ar at e fr o m t h e 
p ati e nt’s  m e di c al r e c or ds,  b ut t h e  p ati e nt  will  b e  a bl e t o  o bt ai n t h e r es e ar c h r e c or ds  aft er 
t h e  c o n cl usi o n  of t h e st u d y 
•   W h et h er t h e  a ut h ori z ati o n  c o nt ai ns  a n  e x pir ati o n  d at e 
•   T h e ri g hts  of  a r es e ar c h  p ati e nt t o r e v o k e  his  or  h er  a ut h ori z ati o n 
I n t h e  e v e nt t h at  a  p ati e nt r e v o k es  a ut h ori z ati o n t o  c oll e ct  or  us e  his  or  h er  P HI, t h e i n v esti g at or, 
b y r e g ul ati o n, r et ai ns t h e  a bilit y t o  us e  all i nf or m ati o n  c oll e ct e d  pri or t o t h e r e v o c ati o n  of  p ati e nt 
a ut h ori z ati o n.   F or  p ati e nts t h at  h a v e r e v o k e d  a ut h ori z ati o n t o  c oll e ct  or  us e  P HI,  att e m pts s h o ul d 
b e  m a d e t o  o bt ai n  p er missi o n t o  c oll e ct  at l e ast  vit al st at us (i. e., t h at t h e  p ati e nt is  ali v e)  at t h e 
e n d  of t h eir s c h e d ul e d st u d y  p eri o d. 
I n  c o m pli a n c e  wit h I C H  G C P  g ui d eli n es  a n d  a p pli c a bl e  p arts  of  2 1  C F R it is  a r e q uir e m e nt t h at 
t h e i n v esti g at or  a n d i nstit uti o n  p er mit  a ut h ori z e d r e pr es e nt ati v es  of t h e S p o ns or, t h e r e g ul at or y 
a ut h oriti es  a n d t h e I R B/ E C  dir e ct  a c c ess t o r e vi e w t h e  p ati e nt’s  ori gi n al  m e di c al r e c or ds  at t h e 
sit e f or  v erifi c ati o n  of  st u d y-r el at e d  pr o c e d ur es  a n d  d at a.  
M e as ur es t o  pr ot e ct  c o nfi d e nti alit y i n cl u d e:  o nl y  a  u ni q u e st u d y  n u m b er  a n d i niti als  will i d e ntif y 
p ati e nts i n t h e  e C R F  or  ot h er  d o c u m e nts s u b mitt e d t o t h e  S p o ns or.   T his i nf or m ati o n, t o g et h er 
wit h t h e  p ati e nt’s  d at e  of  birt h,  will  b e  us e d i n t h e  d at a b as e  f or  p ati e nt i d e ntifi c ati o n.   P ati e nt 
n a m es  or  a d dr ess es  will  n ot  b e  e nt er e d i n t h e  e C R F.   N o  m at eri al  b e ari n g  a  p ati e nt’s  n a m e  will 
b e  k e pt  o n fil e  b y  S p o ns or.   P ati e nts  will  b e i nf or m e d  of t h eir ri g hts  wit hi n t h e I C F/ PI S. 
1 2. 3. 1. 2   I n v esti g at o r  a n d  St aff I nf o r m ati o n 
P ers o n al  d at a  of t h e i n v esti g at ors  a n d s u b-i n v esti g at ors  m a y  b e i n cl u d e d i n t h e  S C RI I n n o v ati o ns 
d at a b as e,  a n d s h all  b e tr e at e d i n  c o m pli a n c e  wit h  all  a p pli c a bl e l a ws  a n d r e g ul ati o ns.   W h e n 
ar c hi vi n g  or  pr o c essi n g  p ers o n al  d at a  p ert ai ni n g t o t h e i n v esti g at or  or s u b i n v esti g at or,  S C RI 
I n n o v ati o ns s h all t a k e  all  a p pr o pri at e  m e as ur es t o s af e g u ar d  a n d  pr e v e nt  a c c ess t o t his  d at a  b y 
a n y  u n a ut h ori z e d  p art y. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 1  of  6 9  
1 2. 4   
Fi n a n ci al I nf o r m ati o n 
T h e fi n a n c es f or t his  cli ni c al  st u d y will  b e  s u bj e ct t o  a s e p ar at e  writt e n  a gr e e m e nt  b et w e e n t h e 
S C RI   D e v el o p m e nt I n n o v ati o ns,  L L C  a n d  a p pli c a bl e  p arti es.   A n y I n v esti g at or fi n a n ci al 
dis cl os ur es  as  a p pli c a bl e t o  2 1 C F R  P art  5 4 s h all  b e  a p pr o pri at el y  pr o vi d e d. 
1 3.   
R E S E A R C H  R E T E N TI O N  A N D  D O C U M E N T A TI O N  O F  T H E  S T U D Y  
1 3. 1   
A m e n d m e nts t o t h e  P r ot o c ol  
A m e n d m e nts t o t h e  pr ot o c ol s h all  b e  pl a n n e d,  d o c u m e nt e d,  a n d si g n at ur e  a ut h ori z e d  pri or t o 
i m pl e m e nt ati o n. 
If  a n  a m e n d m e nt t o t h e  pr ot o c ol is r e q uir e d, t h e  a m e n d m e nt  will  b e  ori gi n at e d  a n d  d o c u m e nt e d 
b y t h e  S p o ns or.   All  a m e n d m e nts r e q uir e r e vi e w  a n d  a p pr o v al  of  all  p h ar m a c e uti c al  c o m p a ni es 
a n d t h e  Pri n ci p al I n v esti g at or s u p p orti n g t h e st u d y.   T h e  writt e n  a m e n d m e nt  m ust  b e r e vi e w e d 
a n d  a p pr o v e d  b y t h e  S p o ns or,  a n d s u b mitt e d t o t h e I R B  at t h e i n v esti g at or’s f a cilit y f or t h e 
b o ar d’s  a p pr o v al. 
A m e n d m e nts s p e cifi c all y i n v ol vi n g  c h a n g e t o st u d y  d esi g n, ris k t o  p ati e nt, i n cr e as e t o  d osi n g  or 
e x p os ur e,  p ati e nt  n u m b er i n cr e as e,  a d diti o n  or r e m o v al  of  n e w t ests  or  pr o c e d ur es, s h all  b e 
r e vi e w e d  a n d  a p pr o v e d  b y t h e I R B of r e c or d f or  t h e I n v esti g at or’s f a cilit y. 
T h e  a m e n d m e nt  will  b e s u b mitt e d f or m all y t o t h e  F D A  or  ot h er r e g ul at or y  a ut h oriti es  b y t h e 
S p o ns or  as  a p pli c a bl e  a n d  I R B/ E C  a p pr o v al  o bt ai n e d,  a n d s p e cifi c all y  w h e n  a n i n cr e as e t o 
d osi n g  or  p ati e nt  e x p os ur e  a n d/ or  p ati e nt  n u m b er  h as  b e e n  pr o p os e d;  or,  w h e n t h e  a d diti o n  or 
r e m o v al  of  a n I n v esti g at or is  n e c essit at e d. 
It e ms r e q uiri n g  a  pr ot o c ol  a m e n d m e nt a p pr o v al fr o m  I R B  a n d/ or  F D A  or  ot h er r e g ul at or y 
a ut h oriti es  i n cl u d e,  b ut  ar e n ot li mit e d t o, t h e f oll o wi n g:  
•   C h a n g e t o st u d y  d esi g n  
•   Ris k t o  p ati e nt 
•   I n cr e as e t o  d os e  or p ati e nt  e x p os ur e t o  dr u g 
•   P ati e nt  n u m b er i n cr e as e  
•   A d diti o n  or r e m o v al  of t ests  a n d /  or  pr o c e d ur es 
•   A d diti o n/r e m o v al  of  a  n e w I n v esti g at or 
It s h o ul d  b e f urt h er  n ot e d t h at, if  a n  a m e n d m e nt t o t h e  pr ot o c ol s u bst a nti all y  alt ers t h e st u d y 
d esi g n  or t h e  p ot e nti al ris ks t o t h e  p ati e nts, t h eir  c o ns e nt t o  c o nti n u e  p arti ci p ati o n i n t h e st u d y 
s h o ul d  b e  o bt ai n e d. 
1 3. 2   
D o c u m e nt ati o n  R e q ui r e d t o I niti at e t h e  St u d y  
B ef or e t h e  st u d y m a y  b e gi n   c ert ai n  d o c u m e nt ati o n r e q uir e d  b y  F D A r e g ul ati o ns a n d I C H  G C P  
m ust  b e  pr o vi d e d  b y t h e I n v esti g at or.   T h e r e q uir e d  d o c u m e nt ati o n s h o ul d  b e s u b mitt e d t o: 
S C RI  I n n o v ati o ns 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 2  of  6 9  
R e g ul at or y  D e p art m e nt  
3 3 2 2  W est  E n d  A v e n u e,  S uit e  9 0 0 
N as h vill e,  T N   3 7 2 0 3 
D o c u m e nts  at  a  mi ni m u m r e q uir e d t o  b e gi n  a  st u d y i n t h e  U S i n cl u d e,  b ut  ar e  n ot li mit e d t o, t h e 
f oll o wi n g: 
•   A si g n at ur e- a ut h ori z e d  pr ot o c ol  a n d  c o ntr a ct 
•   A  c o p y  of t h e  offi ci al I R B / E C  a p pr o v al  of t h e st u d y a n d t h e I R B / E C m e m b ers list  
•   C urr e nt  C urri c ul a  Vit a e  f or t h e  pri n ci p al i n v esti g at or  a n d  a n y  ass o ci at e i n v esti g at or(s) 
w h o  will  b e i n v ol v e d i n t h e st u d y 
•   I n di c ati o n  of  a p pr o pri at e  a c cr e dit ati o n f or  a n y l a b or at ori es t o  b e  us e d i n t h e st u d y  a n d  a 
c o p y  of t h e  n or m al r a n g es f or t ests t o  b e  p erf or m e d  b y t h at l a b or at or y 
•   Ori gi n al  F or m  F D A  1 5 7 2 ( St at e m e nt  of I n v esti g at or),  a p pr o pri at el y  c o m pl et e d  a n d 
si g n e d 
•   A  c o p y  of t h e I R B- a p pr o v e d  c o ns e nt f or m   c o nt ai ni n g  p er missi o n f or  a u dit  b y 
r e pr es e nt ati v es  of  S C RI  I n n o v ati o ns, t h e I R B,  a n d t h e  F D A  a n d  ot h er r e g ul at or y 
a g e n ci es ( as  a p pli c a bl e)  
•   Fi n a n ci al  dis cl os ur e f or ms f or  all i n v esti g at ors list e d  o n  F or m  F D A  1 5 7 2  (if  a p plic a bl e)  
•   Sit e  q u alifi c ati o n r e p orts,  w h er e  a p pli c a bl e  
•   V erifi c ati o n  of  Pri n ci p al I n v esti g at or  a c c e pt a bilit y fr o m l o c al  a n d/ or  n ati o n al  d e b ar m e nt 
list(s)  
 
1 3. 3   
St u d y   D o c u m e nt ati o n  a n d  St o r a g e 
T h e  Pri n ci p al I n v esti g at or  m ust  m ai nt ai n  a list  of  a p pr o pri at el y  q u alifi e d  p ers o ns t o  w h o m  h e/s h e 
h as  d el e g at e d  st u d y  d uti es  a n d s h o ul d  e ns ur e t h at  all  p ers o ns  assisti n g i n t h e  c o n d u ct  of t h e st u d y 
ar e i nf or m e d  of t h eir  o bli g ati o ns.   All  p ers o ns  a ut h ori z e d t o  m a k e  e ntri es  a n d/ or  c orr e cti o ns  o n 
t h e e C R Fs  ar e t o  b e i n cl u d e d  o n t his  d o c u m e nt.   All  e ntri es i n t h e  p ati e nt’s  e C R F  ar e t o  b e 
s u p p ort e d  b y s o ur c e  d o c u m e nt ati o n  w h er e  a p pr o pri at e. 
S o ur c e  d o c u m e nts  ar e t h e  ori gi n al  d o c u m e nts,  d at a,  r e c or ds,  a n d  c ertifi e d  c o pi es  of  ori gi n al 
r e c or ds  of  cli ni c al fi n di n gs,  o bs er v ati o ns, a n d  a ct i viti es fr o m  w hi c h t h e  p ati e nt’s e C R F  d at a  ar e 
o bt ai n e d.   T h es e  c a n i n cl u d e,  b ut  ar e  n ot li mit e d t o,  h os pit al r e c or ds,  cli ni c al  a n d  offi c e  c h arts, 
l a b or at or y,  m e di c o-t e c h ni c al  d e p art m e nt  a n d  p h ar m a c y r e c or ds,  di ari es,  mi cr ofi c h es,  E C G 
tr a c es,  c o pi es  or tr a ns cri pti o ns  c ertifi e d  aft er  v erifi c ati o n  as  b ei n g  a c c ur at e  a n d  c o m pl et e, 
p h ot o gr a p hi c  n e g ati v es,  mi cr ofil m  or  m a g n eti c  m e di a,  X-r a ys,  a n d  c orr es p o n d e n c e. 
T h e  Pri n ci p al I n v esti g at or  a n d  e a c h  st u d y st aff  m e m b er is r es p o nsi bl e f or  m ai nt ai ni n g  a 
c o m pr e h e nsi v e  a n d  c e ntr ali z e d fili n g s yst e m  ( e. g., r e g ul at or y  bi n d er  or i n v esti g at or st u d y fil e 
[I S F]) of  all  st u d y-r el at e d ( ess e nti al)  d o c u m e nt ati o n, s uit a bl e f or i ns p e cti o n  at  a n y ti m e  b y 
r e pr es e nt ati v es fr o m t h e  S p o ns or  a n d/ or  a p pli c a bl e r e g ul at or y  a ut h oriti es.   T h e I S F  m ust  c o nsist 
of t h os e  d o c u m e nts t h at i n di vi d u all y  or  c oll e cti v el y  p er mit  e v al u ati o n  of t h e  c o n d u ct  of t h e st u d y 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 3  of  6 9  
a n d t h e  q u alit y  of t h e  d at a  pr o d u c e d.   T h e I S F s h o ul d  c o nt ai n  as  a  mi ni m u m  all r el e v a nt 
d o c u m e nts  a n d  c orr es p o n d e n c e  as  o utli n e d i n I C H  G C P  S e cti o n  8  a n d  2 1  C F R  P art  3 1 2. 5 7, 
i n cl u di n g  k e y  d o c u m e nts s u c h  as t h e I B  a n d  a n y  a m e n d m e nts,  pr ot o c ol  a n d  a n y  a m e n d m e nts, 
si g n e d I C Fs,  c o pi es  of  c o m pl et e d  e C R F s, I R B  a p pr o v al  d o c u m e nts,  p ati e nt i d e ntifi c ati o n lists, 
e nr oll m e nt l o gs,  d el e g ati o n  of  a ut h orit y l o g, st aff  q u alifi c ati o n  d o c u m e nts, l a b or at or y  n or m al 
r a n g es, r e c or ds r el ati n g t o t h e st u d y  dr u g i n cl u di n g  a c c o u nt a bilit y r e c or ds.   Dr u g  a c c o u nt a bilit y 
r e c or ds s h o ul d,  at  a  mi ni m u m,  c o nt ai n i nf or m ati o n r e g ar di n g r e c ei pt, s hi p m e nt,  a n d  dis p ositi o n.  
E a c h f or m  of  dr u g  a c c o u nt a bilit y r e c or d,  at  a  mi ni m u m, s h o ul d  c o nt ai n  Pri n ci p al I n v esti g at or  
n a m e,  d at e  dr u g s hi p p e d/r e c ei v e d,  d at e,  q u a ntit y  a n d  b at c h/ c o d e,  or l ot  n u m b er f or i d e ntit y  of 
e a c h s hi p m e nt.  I n  a d diti o n,  all  ori gi n al s o ur c e  d o c u m e nts s u p p orti n g  e ntr i es i n t h e e C R F  m ust 
b e  m ai nt ai n e d  a n d  b e r e a dil y  a v ail a bl e.  
T h e  S p o ns or s h all  m ai nt ai n  a d e q u at e i n v esti g ati o n al  pr o d u ct r e c or ds  a n d fi n a n ci al i nt er est 
r e c or ds  as  p er  2 1 C F R  P art  5 4. 6  a n d  P art  3 1 2. 5 7 f or  n o l ess t h a n  2  y e ars  aft er t h e l ast  m ar k eti n g 
a p pli c a ti o n  h as  b e e n  a p pr o v e d  b y t h e F D A;  or, i n t h e  e v e nt t h at t h e  m ar k eti n g  a p pli c ati o n  h as  n ot 
b e e n  a p pr o v e d  b y  t h e F D A, f or  n o l ess t h a n  2  y e ars  aft er t h e l ast s hi p m e nt /  d eli v er y  of t h e  dr u g 
f or i n v esti g ati o n al  us e is  dis c o nti n u e d  a n d t h e F D A  h as  b e e n  n otifi e d  of t h e  dis c o nti n u ati o n. 
T h e I R B s h all  m ai nt ai n  a d e q u at e  d o c u m e nt ati o n / r e c or ds  of I R B  a cti viti es  as  p er  2 1 C F R  P art 
5 6. 1 1 5 f or  at l e ast  3  y e ars  aft er  c o m pl eti o n  of t h e r es e ar c h. 
T h e I n v esti g at or s h all  m ai nt ai n  a d e q u at e r e c or ds  of  dr u g  dis p ositi o n,  c as e  hist ori es , a n d  a n y 
ot h er st u d y-r el at e d r e c or ds  as  p er  2 1  C F R  P art  3 1 2. 6 2 f or  n o l ess t h a n  2  y e ars  aft er t h e l ast 
m ar k eti n g  a p pli c ati o n  h as  b e e n  a p pr o v e d  b y  t h e F D A;  or, i n t h e  e v e nt t h at t h e  m ar k eti n g 
a p pli c ati o n  h as  n ot  b e e n  a p pr o v e d  b y  t h e F D A, f or  n o l e ss t h a n  2  y e ars  aft er t h e l ast s hi p m e nt / 
d eli v er y  of t h e  dr u g f or i n v esti g ati o n al  us e is  dis c o nti n u e d  a n d  t h e F D A  h as  b e e n  n otifi e d  of t h e 
dis c o nti n u ati o n. 
T o  e n a bl e  e v al u ati o ns  a n d/ or  a u dits fr o m r e g ul at or y  a ut h oriti es  or fr o m t h e  S p o ns or  or its 
r e pr es e nt ati v e, t h e i n v esti g at or  a d diti o n all y  a gr e es t o  k e e p r e c or ds, i n cl u di n g t h e i d e ntit y  of  all 
p arti ci p ati n g  p ati e nts (s uffi ci e nt i nf or m ati o n t o li n k r e c or ds  e. g.,  e C R Fs,  m e di c al r e c or ds),  all 
ori gi n al, si g n e d  I C Fs,  a n d  c o pi es  of  all  e C R Fs,  S A E  R e p orti n g f or ms, s o ur c e  d o c u m e nts, 
d et ail e d r e c or ds  of tr e at m e nt  dis p ositi o n,  a n d r el at e d  ess e nti al r e g ul at or y  d o c u m e nts.   T h e 
d o c u m e nts list e d  a b o v e  m ust  b e r et ai n e d  b y t h e i n v esti g at or f or  as l o n g  as  n e e d e d t o  c o m pl y  wit h 
n ati o n al  a n d i nt er n ati o n al r e g ul ati o ns ( g e n er a ll y  2  y e ars  aft er  dis c o nti n ui n g  cli ni c al  d e v el o p m e nt 
or  aft er t h e l ast  m ar k eti n g  a p pr o v al).   S p o ns or  will  n otif y t h e i n v esti g at or(s)/i nstit uti o ns(s)  w h e n 
t h e st u d y-r el at e d re c or ds  ar e  n o l o n g er r e q uir e d. 
If t h e i n v esti g at or r el o c at es, r etir es,  or f or  a n y r e as o n  wit h dr a ws fr o m t h e st u d y,  b ot h t h e S p o ns or 
a n d its r e pr es e nt ati v e s h o ul d  b e  pr os p e cti v el y  n otifi e d.   T h e st u d y r e c or ds  m ust  b e tr a nsf err e d t o 
a n  a c c e pt a bl e  d esi g n e e, s u c h  as  a n ot h er i n v esti g at or,  a n ot h er i nstit uti o n,  or t o t h e  S p o ns or .   T he 
i n v esti g at or  m ust  o bt ai n t h e  S p o ns or’s  writt e n  p er missi o n  b ef or e  dis p osi n g  of  a n y r e c or ds,  e v e n 
if r et e nti o n r e q uir e m e nts  h a v e  b e e n  m et.   All st u d y fil es  will  b e  m ai nt ai n e d  b y t h e S p o ns or 
t hr o u g h o ut t h e st u d y,  a n d  will  b e tr a nsf err e d t o t h e  S p o ns or  at t h e  c o n cl usi o n  of t h e st u d y. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 4  of  6 9  
1 3. 4   
D at a  C oll e cti o n 
T h e  st u d y  eC R F is t h e  pri m ar y  d at a  c oll e cti o n i nstr u m e nt f or t h e  st u d y.   C as e r e p ort f or ms  will 
b e  c o m pl et e d  usi n g t h e  E n glis h l a n g u a g e  a n d s h o ul d  b e  k e pt  c urr e nt t o  e n a bl e t h e  S p o ns or t o 
r e vi e w t h e  p ati e nts’ st at us t hr o u g h out t h e  c o urs e  of t h e  st u d y. 
I n  or d er t o  m ai nt ai n  c o nfi d e nti alit y,  o nl y st u d y  n u m b er,  p ati e nt  n u m b er, i niti als  a n d  d at e  of  birt h 
will i d e ntif y t h e  p ati e nt i n t h e  e C R F.  If t h e  p ati e nt’s  n a m e  a p p e ars  o n  a n y  ot h er  d o c u m e nt ( e. g., 
l a b or at or y r e p ort), it  m ust  b e  o blit er at e d  o n t h e  c o p y  of t h e  d o c u m e nt t o  b e s u p pli e d t o  S C RI 
I n n o v ati o ns  a n d r e pl a c e d i nst e a d  wit h t h e  p ati e nt  n u m b er  a n d  p ati e nt’s i niti als.   T h e i n v esti g at or 
will  m ai nt ai n  a  p ers o n al  p ati e nt i d e ntifi c ati o n list ( p ati e nt  n u m b ers  wit h  c orr es p o n di n g  p ati e nt 
i d e ntifi ers) t o  e n a bl e r e c or ds t o  b e i d e ntifi e d  a n d  v erifi e d  as  a ut h e nti c.   P ati e nt  d at a/i nf or m ati o n 
will  b e  k e pt  c o nfi d e nti al,  a n d  will  b e  m a n a g e d  a c c or di n g t o  a p pli c a bl e l o c al, st at e,  a n d f e d er al 
r e g ul ati o ns. 
All  d at a r e q u est e d  i n t h e  e C R F  m ust  b e s u p p ort e d  b y  a n d  b e  c o nsist e nt  wit h t h e  p ati e nt’s s o ur c e 
d o c u m e nt ati o n.   All  missi n g  d at a  m ust  b e  e x pl ai n e d.   W h e n  a r e q uir e d l a b or at or y t est, 
ass ess m e nt,  or  e v al u ati o n  h as  n ot  b e e n  d o n e  or  a n  “ U n k n o w n ”  b o x is  n ot  a n  o pti o n  o n t h e  e C R F, 
a  n ot e s h o ul d  b e  cr e at e d  v erif yi n g t h at t h e fi el d  w as  “ N ot  D o n e ”  or  “ U n k n o w n. ”   F or  a n y  e ntr y 
err ors  m a d e, t h e  err or(s)  m ust  b e  c orr e ct e d,  a n d  a  n ot e  e x pl ai ni n g t h e r e as o n f or  c h a n g e s h o ul d 
b e  pr o vi d e d. 
T h e i n v esti g at or  will  el e ctr o ni c all y si g n  a n d  d at e t h e  p ati e nt  e C R F  c as e b o o k i n di c ati n g t h at t h e 
d at a i n t h e  e C R F  h as  b e e n  ass ess e d.   E a c h  c o m pl et e d  e C R F  will  b e si g n e d  a n d  d at e d  b y t h e 
Pri n ci p al I n v esti g at or,  o n c e  all  d at a f or t h at  p ati e nt is fi n al.  
1 3. 5   
St u d y  M o nit o ri n g,  A u diti n g,  a n d I ns p e cti n g  
T h e i n v esti g at or  will  p er mit  st u d y-r el at e d  m o nit ori n g,  q u alit y  a u dits,  a n d i ns p e cti o ns  b y t h e 
S p o ns or  or its r e pr es e nt ati v e(s) ,  g o v er n m e nt r e g ul at or y  a ut h oriti es, a n d t h e I R B/ E C  of  all  st u d y-
r el at e d  d o c u m e nts ( e. g., s o ur c e  d o c u m e nts, r e g ul at or y  d o c u m e nts,  d at a  c oll e cti o n i nstr u m e nts, 
c as e r e p ort f or ms).   T h e i n v esti g at or  will  e ns ur e t h e  c a p a bilit y f or i ns p e cti o ns  of  a p pli c a bl e 
st u d y-r el at e d f a ciliti es.   T h e i n v esti g at or  will  e ns ur e t h at t h e st u d y  m o nit or  or  a n y  ot h er 
c o m pli a n c e  or  Q u alit y  Ass ur a n c e r e vi e w er is  gi v e n  a c c ess t o  all  st u d y-r el ate d  d o c u m e nts  a n d 
st u d y-r el at e d f a ciliti es. 
At t h e  S p o ns or’s  dis cr eti o n,  S o ur c e  D o c u m e nt  V erifi c ati o n ( S D V)  m a y  b e  p erf or m e d  o n  all  d at a 
it e ms  or  a  p er c e nt a g e t h er e of. 
P arti ci p ati o n  as  a n i n v esti g at or i n t his  st u d y i m pli es t h e  a c c e pt a n c e  of  p ot e nti al i ns p e cti o n  b y 
g o v er n m e nt r e g ul at or y  a ut h oriti es, t h e  S p o ns or  or its r e pr es e nt ati v e(s). 
1 3. 6   
Q u alit y  Ass u r a n c e  a n d  Q u alit y  C o nt r ol 
E a c h  st u d y sit e s h all  b e r e q uir e d t o  h a v e  St a n d ar d  O p er ati n g  Pr o c e d ur es t o  d efi n e  a n d  e ns ur e 
q u alit y  ass ur a n c e/ c o ntr ol  pr o c ess es f or st u d y  c o n d u ct,  d at a  g e n er ati o n  &  c oll e cti o n, r e c or di n g  of 
d at a/ d o c u m e nt ati o n  a n d r e p orti n g  a c c or di n g t o t h e  pr ot o c ol,  G C P  a n d  a n y  a p pli c a bl e l o c al, 
n ati o n al  or i nt er n ati o n al r e g ul ati o ns. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 5  of  6 9  
1 3. 7   
Dis cl os u r e  a n d  P u bli c ati o n  P oli c y  
All i nf or m ati o n  pr o vi d e d r e g ar di n g t h e st u d y ,  as  w ell  as  all i nf or m ati o n  c oll e ct e d/ d o c u m e nt e d 
d uri n g t h e  c o urs e  of t h e st u d y,  will  b e r e g ar d e d  as  c o nfi d e nti al.   T h e  S p o ns or r es er v es t h e ri g ht 
t o r el e as e lit er at ur e  p u bli c ati o ns  b as e d  o n t h e r es ults  of t h e st u d y.   R es ults fr o m t h e st u d y  will  b e 
p u blis h e d/ pr es e nt e d  as  p er t h e  S p o ns or’s  p u bli c ati o n str at e g y. 
I n cl usi o n  of t h e i n v esti g at or i n t h e  a ut h ors hi p  of  a n y  m ultic e nt er   p u bli c ati o n  will  b e  b as e d  u p o n 
s u bst a nti al  c o ntri b uti o n t o t h e  d esi g n,  a n al ysis, i nt er pr et ati o n  of  d at a,  dr afti n g  a n d/ or  criti c all y 
r e visi n g  a n y  m a n us cri pt(s)  d eri v e d fr o m t h e st u d y.   T h e i n v esti g at or  a c k n o wl e d g es t h at t h e st u d y 
is  p art  of  a  m ultic e nt er  st u d y  a n d  a gr e es t h at  a n y  p u bli c ati o n  b y t h e i n v esti g at or  of t h e r es ults  of 
t h e st u d y c o n d u ct e d  at r es e ar c h sit e s h all  n ot  b e  m a d e  b ef or e t h e first  m ulti c e nt er   p u bli c ati o n.  I n 
t h e  e v e nt t h er e is  n o  m ultic e nt er   p u bli c ati o n  wit hi n fift e e n ( 1 5)  m o nt hs  aft er t h e st u d y h as  b e e n 
c o m pl et e d  or t er mi n at e d  at  all  st u d y sit es,  a n d  all  d at a  h as  b e e n r e c ei v e d, t h e i n v esti g at or s h all 
h a v e t h e ri g ht t o  p u blis h its r es ults fr o m t h e  st u d y, s u bj e ct t o t h e  n oti c e r e q uir e m e nts  d es cri b e d 
h er ei n  a n d s u bj e ct t o  a c k n o wl e d g e m e nt  of t h e  S p o ns or  as  a p pr o pri at e.  I n v esti g at or s h all  pr o vi d e 
t h e  S p o ns or t hirt y ( 3 0)  d a ys t o r e vi e w  a  m a n us cri pt  or  a n y  p ost er  pr es e nt ati o n,  a bstr a ct  or  ot h er 
writt e n  or  or al  m at eri al  w hi c h  d es cri b es t h e r es ults  of t h e  st u d y f or t h e  p ur p os e  o nl y  of 
d et er mi ni n g if  a n y  c o nfi d e nti al  or  p at e nt a bl e i nf or m ati o n is  dis cl os e d t h er e b y.  If t h e  S p o ns or 
r e q u ests i n  writi n g, t h e i n v esti g at or s h all  wit h h ol d  a n y  p u bli c ati o n  or  pr es e nt ati o n  a n  a d diti o n al 
si xt y ( 6 0)  d a ys s ol el y t o  p er mit t h e  S p o ns or t o s e e k  p at e nt  pr ot e cti o n  a n d t o r e m o v e  a n y  S C RI 
I n n o v ati o ns C o nfi d e nti al I nf or m ati o n fr o m  all  p u bli c ati o ns.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 6  of  6 9  
1 4.   
R E F E R E N C E S  
A d v a n c e d  Bl a d d e r  C a n c e r  C oll a b o r at i o n  2 0 0 5 
A d v a n c e d  Bl a d d er  C a n c er  M et a -a n al ysis  C oll a b or ati o n.  N e o a dj u v a nt  c h e m ot h er a p y i n i n v asi v e 
bl a d d er  c a n c er:  u p d at e  of  a s yst e m ati c r e vi e w  a n d  m et a - a n al ysis  of i n di vi d u al  p ati e nt  d at a 
a d v a n c e d  bl a d d er  c a n c er ( A B C)  m et a - a n al ysis  c oll a b or ati o n.  E ur  Ur ol  2 0 0 5;  4 8:  2 0 2- 2 0 5; 
dis c ussi o n  2 0 5- 2 0 6. 
B aj o ri n  et  al.  1 9 9 9 
B aj ori n  D F,  D o d d  P M,  M a z u m d ar  M  et  al.  L o n g- t er m s ur vi v al i n  m et ast ati c tr a nsiti o n al-c ell 
c ar ci n o m a  a n d  pr o g n osti c f a ct ors  pr e di cti n g  o ut c o m e  of t h er a p y. J  Cli n  O n c ol  1 9 9 9;  1 7:  3 1 7 3-
3 1 8 1. 
B al a r  et  al.  2 0 1 3 
B al ar  A V,  A p ol o  A B,  Ostr o v n a y a I  et  al.  P h as e II st u d y  of  g e m cit a bi n e,  c ar b o pl ati n,  a n d 
b e v a ci z u m a b i n  p ati e nts  wit h  a d v a n c e d  u nr es e ct a bl e  or  m et ast ati c  ur ot h eli al  c a n c er. J  Cli n  O n c ol 
2 0 1 3;  3 1:  7 2 4- 7 3 0. 
B ell m u nt  et  al.  2 0 1 2 
B ell m u nt J,  v o n  d er  M a as e  H,  M e a d  G M  et  al.  R a n d o mi z e d  p h as e III st u d y  c o m p ari n g 
p a clit a x el/ cis pl ati n/ g e m cit a bi n e  a n d  g e m cit a bi n e/ cis pl ati n i n  p ati e nts  wit h l o c all y  a d v a n c e d  or 
m et ast ati c  ur ot h eli al  c a n c er  wit h o ut  pri or s yst e mi c t h er a p y:  E O R T C I nt er gr o u p  St u d y  3 0 9 8 7. J 
Cli n  O n c ol  2 0 1 2;  3 0:  1 1 0 7- 1 1 1 3. 
D as h  et  al.  2 0 0 6 
D as h  A,  G als k y  M D,  Vi c k ers  AJ  et  al. I m p a ct  of r e n al i m p air m e nt  o n  eli gi bilit y f or  a dj u v a nt 
cis pl ati n - b as e d  c h e m ot h er a p y i n  p ati e nts  wit h  ur ot h eli al  c ar ci n o m a  of t h e  bl a d d er.  C a n c er  2 0 0 6; 
1 0 7:  5 0 6- 5 1 3.  
D e  S a ntis   et  al.  2 0 1 2 
D e  S a ntis  M,  B ell m u nt J,  M e a d  G  et  al.  R a n d o mi z e d  p h as e  II/III tri al  ass essi n g 
g e m cit a bi n e/ c ar b o pl ati n  a n d  m et h otr e x at e/ c ar b o pl ati n/ vi n bl asti n e i n  p ati e nts  wit h  a d v a n c e d 
ur ot h eli al  c a n c er  w h o  ar e  u nfit f or  cis pl ati n- b as e d  c h e m ot h er a p y:  E O R T C st u d y  3 0 9 8 6. J  Cli n 
O n c ol  2 0 1 2;  3 0:  1 9 1- 1 9 9. 
G als k y   et  al.  2 0 1 1 a 
G als k y  M D,  H a h n  N M,  R os e n b er g J  et  al.  A  c o ns e ns us  d efi niti o n  of  p ati e nts  wit h  m et ast ati c 
ur ot h eli al  c ar ci n o m a  w h o  ar e  u nfit f or  cis pl ati n - b as e d  c h e m ot h er a p y.  L a n c et  O n c ol  2 0 1 1;  1 2: 
2 1 1- 2 1 4. 
G a ls k y  et  al.  2 0 1 1 b 
G als k y  M D,  H a h n  N M,  R os e n b er g J  et  al.  Tr e at m e nt  of  p ati e nts  wit h  m et ast ati c  ur ot h eli al  c a n c er 
" u nfit " f or  Cis pl ati n - b as e d  c h e m ot h er a p y. J  Cli n  O n c ol  2 0 1 1;  2 9:  2 4 3 2- 2 4 3 8. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 7  of  6 9  
G als k y   et  al.  2 0 1 2 
G als k y  M D,  C h e n  GJ,  O h  W K  et  al.  C o m p ar ati v e  eff e cti v e n ess  of  cis pl ati n - b as e d  a n d 
c ar b o pl ati n -b as e d  c h e m ot h er a p y f or tr e at m e nt  of  a d v a n c e d  ur ot h eli al  c ar ci n o m a.  A n n  O n c ol 
2 0 1 2;  2 3:  4 0 6- 4 1 0. 
G r a dis h a r  et  al.  2 0 0 9 
Gr a dis h ar  WJ,  Kr as n oj o n  D,  C h e p ar o v  S,  et  al.  Si g nifi c a ntl y l o n g er  pr o gr essi o n- fr e e s ur vi v al 
wit h  n a b- p a clit a x el  c o m p ar e d  wit h  d o c et a x el  as first -li n e t h er a p y f or  m et ast ati c  br e ast  c a n c er. J 
Cli n  O n c ol.  2 0 0 9;  2 7: 3 6 1 1- 3 6 1 9. 
G r oss m a n  et  al.  2 0 0 3 
Gr oss m a n  H B,  N at al e  R B,  T a n g e n  C M  et  al.  N e o a dj u v a nt  c h e m ot h er a p y  pl us  c yst e ct o m y 
c o m p ar e d  wit h  c yst e ct o m y  al o n e f or l o c all y  a d v a n c e d  bl a d d er  c a n c er.  N  E n gl J  M e d  2 0 0 3;  3 4 9: 
8 5 9- 8 6 6. 
I nt e r n ati o n al  Bl a d d e r  C a n c e r  N o m o g r a m  C o n s o rti u m  et  al.  2 0 0 6 
I nt er n ati o n al  Bl a d d er  C a n c er  N o m o gr a m  C o ns orti u m,  B o c h n er  B H,  K att a n  M W,  V or a  K C. 
P ost o p er ati v e  n o m o gr a m  pr e di cti n g  ris k  of r e c urr e n c e  aft er r a di c al  c yst e ct o m y f or  bl a d d er 
c a n c er. J  Cli n  O n c ol  2 0 0 6;  2 4:  3 9 6 7- 3 9 7 2. 
I nt e r n ati o n al  C oll a b o r ati o n  of  T ri alist  2 0 1 1 
I nt er n ati o n al  C oll a b or ati o n  of  Tri alist,  M e di c al  R es e ar c h  C o u n cil  A d v a n c e d  Bl a d d er  C a n c er 
W or ki n g  P,  E ur o p e a n  Or g a nis ati o n f or  R  et  al. I nt er n ati o n al  P h as e  III tri al  ass essi n g  n e o a dj u v a nt 
cis pl ati n,  m et h otr e x at e,  a n d  vi n bl asti n e  c h e m ot h er a p y f or  m us cl e-i n v asi v e  bl a d d er  c a n c er: l o n g-
t er m r es ults  of t h e  B A 0 6  3 0 8 9 4 tri al. J  Cli n  O n c ol  2 0 1 1;  2 9:  2 1 7 1- 2 1 7 7. 
K o  et  al.  2 0 1 3 
K o  YJ,  C a nil  C M,  M u k h erj e e  S D  et  al.  N a n o p arti cl e  al b u mi n- b o u n d  p a clit a x el f or s e c o n d- li n e 
tr e at m e nt  of  m et ast ati c  ur ot h eli al  c ar ci n o m a:  a si n gl e  gr o u p,  m ulti c e ntr e,  p h as e  2 st u d y.  L a n c et 
O n c ol  2 0 1 3;  1 4:  7 6 9- 7 7 6. 
L o e h r e r   et  al.  1 9 9 2 
L o e hr er  PJ,  Sr.,  Ei n h or n  L H,  Els o n  PJ  et  al.  A r a n d o mi z e d  c o m p aris o n  of  cis pl ati n  al o n e  or i n 
c o m bi n ati o n  wit h  m et h otr e x at e,  vi n bl asti n e,  a n d  d o x or u bi ci n i n  p ati e nts  wit h  m et ast ati c 
ur ot h eli al  c ar ci n o m a:  a  c o o p er ati v e  gr o u p st u d y. J  Cli n  O n c ol  1 9 9 2;  1 0:  1 0 6 6- 1 0 7 3. 
L o g ot h etis  et   al.  1 9 9 0 
L o g ot h etis  CJ,  D e x e us  F H,  Fi n n  L  et  al.  A  pr os p e cti v e r a n d o mi z e d tri al  c o m p ari n g  M V A C  a n d 
CI S C A  c h e m ot h er a p y f or  p ati e nts  wit h  m et ast ati c  ur ot h eli al t u m ors. J   Cli n  O n c ol  1 9 9 0;  8:  1 0 5 0-
1 0 5 5. 
P o d h aj c e r  et  al.  2 0 0 8 
P o d h aj c er  O L,  B e n e d etti  L G,  Gir ott i  M R  et  al.  T h e r ol e  of t h e  m atri c ell ul ar  pr ot ei n  S P A R C i n 
t h e  d y n a mi c i nt er a cti o n  b et w e e n t h e t u m or  a n d t h e  h ost.  C a n c er  M et ast asis  R e v  2 0 0 8;  2 7:  6 9 1-
7 0 5. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 8  of  6 9  
 
S a x m a n  et  al.  1 9 9 7 
S a x m a n  S B,  Pr o p ert  KJ,  Ei n h or n  L H  et  al.  L o n g- t er m f oll o w- u p  of  a P h as e  III i nt er gr o u p st u d y 
of  cis pl ati n  al o n e  or i n  c o m bi n ati o n  wit h  m et h otr e x at e,  vi n bl asti n e,  a n d  d o x or u bi ci n i n  p ati e nts 
wit h  m et ast ati c  ur ot h eli al  c ar ci n o m a:  a  c o o p er ati v e  gr o u p st u d y. J  Cli n  O n c ol  1 9 9 7;  1 5:  2 5 6 4-
2 5 6 9. 
S h a ri at  et  al.  2 0 0 6 a 
S h ari at  S F,  K ar a ki e wi c z  PI ,  P al a p att u  G S  et  al.  O ut c o m es  of r a di c al  c yst e ct o m y f or tr a nsiti o n al 
c ell  c ar ci n o m a  of t h e  bl a d d er:  a  c o nt e m p or ar y s eri es fr o m t h e  Bl a d d er  C a n c er  R es e ar c h 
C o ns orti u m. J  Ur ol  2 0 0 6;  1 7 6:  2 4 1 4- 2 4 2 2;  dis c ussi o n  2 4 2 2. 
S h a ri at  et  al.  2 0 0 6 b 
S h ari at  S F,  K ar a ki e wi c z  PI,  P al a p att u  G S  et  al.  N o m o gr a ms  pr o vi d e i m pr o v e d  a c c ur a c y f or 
pr e di cti n g s ur vi v al  aft er r a di c al  c yst e ct o m y.  Cli n  C a n c er  R es  2 0 0 6;  1 2:  6 6 6 3- 6 6 7 6. 
Si e g el  et  al.  2 0 1 5 
Si e g el  R,  Mill er  K D, J e m al  A.  C a n c er st atisti cs,  2 0 1 5.  C A  C a n c er J  Cli n  2 0 1 5 ;  65 : 5- 2 9. 
S o ci ns ki  et  al.  2 0 1 2 
S o ci ns ki  M A,  B o n d ar e n k o I,  K ar as e v a  N A,  et  al.  W e e kl y  n a b- p a clit a x el i n  c o m bi n ati o n  wit h 
c ar b o pl ati n  v ers us s ol v e nt- b as e d  p a clit a x el  pl us  c ar b o pl ati n  as first -li n e t h er a p y i n  p ati e nts  wit h 
a d v a n c e d  n o n- s m all-c ell l u n g  c a n c er:  Fi n al r e s ults  of  a  p h as e III tri al. J  Cli n  O n c ol.  2 0 1 2;  3 0: 
2 0 5 5- 2 0 6 2. 
S o n p a v d e   et  al.  2 0 1 2 
S o n p a v d e  G,  W ats o n  D,  T o urt ell ott  M  et  al.  A d mi nistr ati o n  of  cis pl ati n- b as e d  c h e m ot h er a p y f or 
a d v a n c e d  ur ot h eli al  c ar ci n o m a i n t h e  c o m m u nit y.  Cli n  G e nit o uri n  C a n c er  2 0 1 2;  1 0:  1- 5. 
S o n p a v d e   et  al.  2 0 1 3 
S o n p a v d e  G,  G als k y  M D,  B ell m u nt J.  A  n e w  a p pr o a c h t o s e c o n d- li n e t h er a p y f or  ur ot h eli al 
c a n c er ?  L a n c et  O n c ol  2 0 1 3;  1 4:  6 8 2- 6 8 4. 
S o n p a v d e   et  al.  2 0 1 4 
S o n p a v d e  G,  G als k y  M D,  L ati ni  D,  C h e n  GJ.  Cis pl ati n- i n eli gi bl e  a n d  c h e m ot h er a py- i n eli gi bl e 
p ati e nts s h o ul d  b e t h e f o c us  of  n e w  dr u g  d e v el o p m e nt i n  p ati e nts  wit h  a d v a n c e d  bl a d d er  c a n c er. 
Cli n  G e nit o uri n  C a n c er  2 0 1 4;  1 2:  7 1- 7 3. 
St ei n  et  al.  2 0 0 6 
St ei n J P,  S ki n n er  D G.  R a di c al  c yst e ct o m y f or i n v asi v e  bl a d d er  c a n c er: l o n g- t er m r es ults  of a 
st a n d ar d  pr o c e d ur e.  W orl d J  Ur ol  2 0 0 6;  2 4:  2 9 6- 3 0 4. 
 
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  5 9  of  6 9  
St e r n b e r g   et  al.  2 0 0 6 
St er n b er g  C N,  d e  M ul d er  P,  S c h or n a g el J H  et  al.  S e v e n  y e ar  u p d at e  of  a n  E O R T C  p h as e III tri al 
of  hi g h- d os e i nt e nsit y  M- V A C  c h e m ot h er a p y  a n d  G -C S F  v ers us  cl assi c  M - V A C i n  a d v a n c e d 
ur ot h eli al tr a ct t u m o urs.  E ur J  C a n c er  2 0 0 6;  4 2:  5 0- 5 4. 
v o n  d e r  M a as e  et  al.  2 0 0 0 
v o n  d er  M a as e  H,  H a ns e n  S W,  R o b erts J T  et  al.  G e m cit a bi n e  a n d  cis pl ati n  v ers us  m et h otr e x at e, 
vi n bl asti n e,  d o x or u bi ci n,  a n d  cis pl ati n i n  a d v a n c e d  or  m et ast ati c  bl a d d er  c a n c e r: r es ults  of  a 
l ar g e, r a n d o mi z e d,  m ulti n ati o n al,  m ulti c e nt er,  p h as e III st u d y. J  Cli n  O n c ol  2 0 0 0;  1 8:  3 0 6 8- 3 0 7 7. 
v o n  d e r  M a as e  et  al.  2 0 0 5 
v o n  d er  M a as e  H,  S e n g el o v  L,  R o b erts J T  et  al.  L o n g- t er m s ur vi v al r es ults  of  a r a n d o mi z e d tri al 
c o m p ari n g  g e m cit a bi n e  pl us  cis pl ati n,  wit h  m et h otr e x at e,  vi n bl asti n e,  d o x or u bi ci n,  pl us  cis pl ati n 
i n  p ati e nts  wit h  bl a d d er  c a n c er. J  Cli n  O n c ol  2 0 0 5;  2 3:  4 6 0 2- 4 6 0 8. 
V o n  H off  et  al.  2 0 1 1 
V o n  H off  D D,  R a m a n at h a n  R K,  B or a d  MJ  et  al.  G e m cit a bi n e  pl us  n a b- p a clit a x el is  a n  a cti v e 
r e gi m e n i n  p ati e nts  wit h  a d v a n c e d  p a n cr e ati c  c a n c er:  a  p h as e I/II tri al. J  Cli n  O n c ol  2 0 1 1;  2 9: 
4 5 4 8- 4 5 5 4. 
V o n  H off  et  al.  2 0 1 3 
V o n  H off  D D,  Er vi n  T,  Ar e n a  F P  et  al. I n cr e as e d s ur vi v al i n  p a n cr e ati c  c a n c er  wit h  n a b-
p a clit a x el  pl us  g e m cit a bi n e.  N  E n gl J  M e d  2 0 1 3;  3 6 9:  1 6 9 1- 1 7 0 3. 
 
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 0  of  6 9  
1 5.   
A P P E N DI C E S  
 
A p p e n di x  A:  E C O G  P e rf o r m a n c e  St at us  C rit e ri a  
 
E C O G  P e rf o r m a n c e  St at us  S c al e  
 
K a r n ofs k y  P e rf o r m a n c e  S c al e  
G r a d e  
D es c ri pti o ns  
P e r c e nt  
D es c ri pti o n  
0 
N or m al  a cti vit y.  F ull y  a cti v e,  a bl e t o  c arr y 
o n  all  pr e -dis e as e  p erf or m a n c e  wit h o ut 
r estri cti o n. 
 
1 0 0  
N or m al,  n o  c o m pl ai nts,  n o  e vi d e n c e  of 
dis e as e.  
 
9 0  
A bl e t o  c arr y  o n  n or m al  a cti vit y;  mi n or 
si g ns  or s y m pt o ms  of  dis e a s e.  
1 
S y m pt o ms,  b ut  a m b ul at or y.   R estri ct e d i n 
p h ysi c all y  str e n u o us  a cti v it y,  b ut 
a m b ul at or y  a n d  a bl e t o  c arr y  o ut  w or k  of  a 
li g ht  or s e d e nt ar y  n at ur e ( e. g., li g ht 
h o us e w or k,  offi c e  w or k).  
 
8 0  
N or m al  a cti vit y  wit h  eff ort; s o m e si g ns  or 
s y m pt o ms  of  dis e as e.  
 
7 0  
C ar es f or s elf,  u n a bl e t o  c arr y  o n  n or m al 
a cti vit y  or t o  d o  a cti v e  w or k.  
2 
I n  b e d < < 5 0 %  of t h e ti m e.   A m b ul at or y  a n d 
c a p a bl e  of  all s elf -c ar e,  b ut  u n a bl e t o  c arr y 
o ut  a n y  w or k  a cti viti es.   U p  a n d  a b o ut  m or e 
t h a n  5 0 %  of  w a ki n g  h o ur s. 
 
6 0  
R e q uir es  o c c asi o n al  assist a n c e,  b ut is  a bl e 
t o  c ar e f or  m ost  of  his/ h er  n e e ds. 
 
5 0  
R e q uir es  c o nsi d er a bl e  assist a n c e  a n d 
fr e q u e nt  m e di c al  c ar e. 
3 
I n  b e d > >  5 0 %  of t h e ti m e.   C a p a bl e  of  o nl y 
li mit e d s elf-c ar e,  c o nfi n e d t o  b e d  or  c h air 
m or e t h a n  5 0 %  of  w a ki n g  h o urs.  
 
4 0  
Dis a bl e d, r e q uir es s p e ci al  c ar e  a n d 
assist a n c e  
 
3 0  
S e v er el y  dis a bl e d,  h os pit ali z ati o n 
i n di c at e d.   D e at h  n o i m mi n e nt. 
4 
1 0 0 %  b e dri d d e n.   C o m pl et el y  dis a bl e d.  
C a n n ot  c arr y  o n  a n y s elf -c ar e.   T ot all y 
c o nfi n e d t o  b e d  or  c h air.  
 
2 0  
V er y si c k,  h os pit ali z ati o n i n di c at e d.   D e at h 
n ot i m mi n e nt.  
 
1 0  
M ori b u n d, f at al  pr o c ess es  pr o gr essi n g 
r a pi dl y. 
5 
D e a d  
0 
D e a d  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 1  of  6 9  
 
A p p e n di x  B:    N e w  Y o r k  H e a rt  Ass o ci ati o n ( N Y H A)  Cl assifi c ati o n  of  C a r di a c  Dis e as e 
T h e f oll o wi n g t a bl e  pr es e nts t h e  N Y H A  cl a ssifi c ati o n  of  c ar di a c  dis e as e.  
Cl ass   
F u n cti o n al  C a p a cit y  
O bj e ct i v e  Ass ess m e nt 
I  
P ati e nts  wit h  c ar di a c  dis e as e  b ut  wit h o ut r es ulti n g li mit ati o ns  of  p h ysi c al 
a cti vit y.   Or di n ar y  p h ysi c al  a cti vit y  d o es  n ot  c a us e  u n d u e f ati g u e, 
p al pit ati o n,  d ys p n e a,  or  a n gi n al  p ai n.  
N o  o bj e cti v e  e vi d e n c e  of 
c ar di o v as c ul ar  dis e as e.  
II  
P a ti e nts  wit h  c ar di a c  dis e as e r es ulti n g i n sli g ht li mit ati o n  of  p h ysi c al 
a cti vit y.   T h e y  ar e  c o mf ort a bl e  at r est.   Or di n ar y  p h ysi c al  a cti vit y r es ults i n 
f ati g u e,  p al pit ati o n,  d ys p n e a,  or  a n gi n al  p ai n. 
O bj e cti v e  e vi d e n c e  of 
mi ni m al  c ar di o v as c ul ar 
dis e as e.  
III  
P ati e nts  wit h  c ar di a c  dis e as e r es ulti n g i n  m ar k e d li mit ati o n  of  p h ysi c al 
a cti vit y.   T h e y  ar e  c o mf ort a bl e  at r est.   L ess t h a n  or di n ar y  a cti vit y  c a us es 
f ati g u e,  p al pit ati o n,  d ys p n e a,  or  a n gi n al  p ai n. 
O bj e cti v e  e vi d e n c e  of 
m o d er at el y s e v er e 
c ar di o v as c ul ar  d is e as e. 
I V  
P ati e nts  wit h  c ar di a c  dis e as e r es ulti n g i n i n a bilit y t o  c arr y  o n  a n y  p h ysi c al 
a cti vit y  wit h o ut  dis c o mf ort.   S y m pt o ms  of  h e art f ail ur e  or t h e  a n gi n al 
s y n dr o m e  m a y  b e  pr es e nt  e v e n  at r est.  If  a n y  p h ysi c al  a cti vit y is  u n d ert a k e n, 
dis c o mf ort is i n cr e as e d.  
O bj e cti v e  e vi d e n c e  of 
s e v er e  c ar di o v as c ul ar 
dis e as e.  
S o ur c e:   T h e  Crit eri a  C o m mitt e e  of  N e w  Y or k  H e art  Ass o ci ati o n.   N o m e n cl at ur e  a n d  Crit eri a f or  Di a g n o sis  of 
Dis e as e s  of t h e  H e art  a n d  Gr e at  V ess els.   9t h  E d.  B ost o n,  M A:   Littl e,  Br o w n  &  C o;  1 9 9 4: 2 5 3 -2 5 6.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 2  of  6 9  
A p p e n di x  C:  G ui d eli n es f o r  F e m al e  P ati e nt s  of  C hil db e a ri n g   P ot e nti al  a n d F e rtil e  M al e 
P ati e nt s 
 
A c c e pt a bl e  C o nt r a c e pti o n  M et h o ds:    
W o m e n  of  c hil d b e ari n g  p ot e nti al,  d efi n e d  as  all  w o m e n  p h ysi ol o gi c all y  c a p a bl e  of  b e c o mi n g 
pr e g n a nt,  m ust  us e  hi g hl y  eff e cti v e  c o ntr a c e pti o n  d uri n g t h e st u d y  a n d f or  3  m o nt hs  aft er 
st o p pi n g tr e at m e nt.   
Hi g hl y  eff e cti v e  c o ntr a c e pti o n is  d efi n e d  as  eit h er: 
T r u e  A bsti n e n c e     
W h e n t his is i n li n e  wit h t h e  pr ef err e d  a n d  us u al lif est yl e  of t h e s u bj e ct. 
P eri o di c  a bsti n e n c e ( e. g.,  c al e n d ar,  o v ul ati o n, s y m pt ot h er m al,  p ost-
o v ul ati o n  m et h o ds)  a n d  wit h dr a w al  ar e  n ot  a c c e pt a bl e  m et h o ds  of 
c o ntr a c e pti o n. 
St e rili z ati o n    
W h e n  a  w o m a n  of  c hil d b e ari n g  p ot e nti al  h as  h a d s ur gi c al  bil at er al 
o o p h or e ct o m y ( wit h  or  wit h o ut  h yst er e ct o m y)  or t u b al li g ati o n  at l e ast 
si x  w e e ks  pri or t o st u d y  e ntr y.  I n  c as e  of  o o p h or e ct o m y  al o n e,  o nl y 
w h e n t h e r e pr o d u cti v e st at us  of t h e  w o m a n  h as  b e e n  c o nfir m e d  b y 
f oll o w  u p  h or m o n e l e v el  ass ess m e nt. 
M al e  P a rt n e r  St e rili z ati o n   W h e n  t h e  a p pr o pri at e  p ost- v as e ct o m y  d o c u m e nt ati o n  of t h e 
a bs e n c e  of s p er m i n t h e  ej a c ul at e . 
Us e  of  a  c o m bi n ati o n  of  a n y t w o  of t h e f oll o wi n g ( o n e f r o m  a  +  o n e f r o m  b):  
a)   Pl a c e m e nt  of  a n i ntr a ut eri n e  d e vi c e (I U D)  or i ntr a ut eri n e s yst e m 
(I U S) or  est a blis h e d  us e  of  or al, i nj e ct e d  or i m pl a nt e d  h or m o n al 
m et h o ds  of  c o ntr a c e pti o n.  
b)   B arri er  m et h o ds  of  c o ntr a c e pti o n:  C o n d o m  or  O c cl usi v e  c a p 
( di ap hr a g m  or  c er vi c al/ v a ult  c a ps)  wit h s p er mi ci d al 
f o a m/ g el/fil m/ cr e a m/ v a gi n al s u p p osit or y. 
F ertil e  m al e  p ati e nts ,  d efi n e d  as  all  m al es  p h ysi ol o gi c all y  c a p a bl e  of  c o n c ei vi n g  offs pri n g, 
wit h f e m al e  p art n ers  of  c hil d -b e ari n g  p ot e nti al  m ust  us e  c o n d o ms  pl us s p er mi ci d al  a g e nt 
d uri n g t h e st u d y tr e at m e nt  p eri o d  a n d f or  6  m o nt hs  aft er t h e l ast  d os e  of st u d y  dr u g,  a n d 
s h o ul d  n ot f at h er  a  c hil d   d uri n g t his  p eri o d. 
M al e  p ati e nts  m ust  als o r efr ai n fr o m  d o n ati n g s p er m  d uri n g t h eir  p arti ci p ati o n i n t h e st u d y.  
T h e f oll o wi n g  a r e  a c c e pt a bl e f o r ms  of  b a r ri e r  c o nt r a c e pti o n:  
•   L at e x  c o n d o m,  di a p hr a g m  or  c er vi c al/ v a ult  c a p  w h e n  us e d  wit h s p er mi ci d al 
f o am/ g el/fil m/ cr e a m/s u p p osit or y  
U n a c c e pt a bl e  C o nt r a c e pti o n  M et h o ds:  f or  w o m e n  of  c hil d b e ari n g  p ot e nti al i n cl u d e: 
•   I U D  pr o g est er o n e  T 
•   F e m al e  c o n d o m  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 3  of  6 9  
•   N at ur al f a mil y  pl a n ni n g (r h yt h m  m et h o d)  or  br e astf e e di n g  
•   F ertilit y  a w ar e n ess  
•   Wit h dr a w al  
•   C er vi c al s hi el d  
P r e g n a n ci es  
T o  e ns ur e s u bj e ct s af et y,  e a c h  pr e g n a n c y i n  a s u bj e ct  o n st u d y tr e at m e nt  m ust  b e r e p ort e d t o 
t h e  S C RI I n n o v ati o ns  S af et y  D e p art m e nt  wit hi n  2 4  h o urs  of l e ar ni n g  of its  o c c urr e n c e.  T h e 
pr e g n a n c y s h o ul d  b e f oll o w e d  u p f or  3  m o nt hs  aft er t h e t er mi n ati o n  of t h e  pr e g n a n c y t o 
d et er mi n e  o ut c o m e, i n cl u di n g s p o nt a n e o us  or  v ol u nt ar y t er mi n ati o n,  d et ails  of t h e  birt h,  a n d 
t h e  pr es e n c e  or  a bs e n c e  of  a n y  birt h  d ef e cts,  c o n g e nit al  a b n or m aliti es,  or  m at er n al  a n d/ or 
n e w b or n  c o m pli c ati o ns. 
If  a f e m al e  p art n er  of  a  m al e  pati e nt  b e c o m es  pr e g n a nt  d uri n g t h e  m al e  p ati e nt’s  p arti ci p ati o n 
i n t his st u d y, d uri n g tr e at m e nt  or f or  6  m o nt hs  aft er st o p pi n g tr e at m e nt, t h e  m al e s u bj e ct t a ki n g 
st u d y  dr u gs s h o ul d  n otif y t h e st u d y  d o ct or,  a n d t h e  pr e g n a nt f e m al e  p art n er s h o ul d  b e  a d vis e d 
t o  c all t h eir  h e alt h c ar e  pr o vi d er i m m e di at el y.  
Pr e g n a n c y s h o ul d  b e r e c or d e d  o n  a  Cli ni c al  St u d y  Pr e g n a n c y  F or m  a n d r e p ort e d  b y t h e 
i n v esti g at or t o S C RI  I n n o v ati o ns S af et y  D e p a rt m e nt .   Pr e g n a n c y f oll o w- u p s h o ul d  b e 
r e c or d e d  o n t h e s a m e f or m  a n d s h o ul d i n cl u d e  a n  ass ess m e nt  of t h e  p ossi bl e r el ati o ns hi p t o t h e 
st u d y  dr u g  of  a n y  pr e g n a n c y  o ut c o m e.   A n y  S A E  e x p eri e n c e d  d uri n g  pr e g n a n c y  m ust  b e 
r e p ort e d  o n t h e  S A E  R e p ort  F or m. 
Pr e g n a n c y  o ut c o m es  m ust  b e  c oll e ct e d f or t h e f e m al e  p art n ers  of  a n y  m al es  w h o t o o k st u d y 
tr e at m e nt i n t his st u d y.   C o ns e nt t o r e p ort i nf or m ati o n r e g ar di n g t h es e  pr e g n a n c y  o ut c o m es 
s h o ul d  b e  o bt ai n e d fr o m t h e  m ot h er. 
W o m e n  N ot  of  C hil d b e a ri n g  P ot e nti al  a r e  d efi n e d  as  F oll o ws:   
•   W o m e n  ar e  c o nsi d er e d  p ost- m e n o p a us al  a n d  n ot  of  c hil d b e ari n g  p ot e nti al if t h e y  h a v e 
h a d  1 2  m o nt hs  of  n at ur al (s p o nt a n e o us)  a m e n orr h e a  wit h  a n  a p pr o pri at e  cli ni c al  pr ofil e 
( e. g.,  a g e  a p pr o pri at e,  hist or y  of  v as o m ot or s y m pt o ms).  
•   W o m e n  w h o  ar e  p er m a n e ntl y st erili z e d ( e. g., t u b al  o c cl usi o n,  h yst er e ct o m y,  bil at er al 
s al pi n g e ct o m y,  bil at er al  o o p h or e ct o m y).   
•   W o m e n  w h o  ar e  > 4 5  y e ars- of- a g e,  n ot  usi n g  h or m o n e- r e pl a c e m e nt t h er a p y  a n d  w h o 
h a v e  e x p eri e n c e d t ot al  c ess ati o n  of  m e ns es f or  at l e ast  1 2  m o nt hs  O R  w h o  h a v e  a 
f olli cl e sti m ul ati n g  h or m o n e ( F S H)  v al u e  > 4 0 mI U/ m L  a n d  a n  estr a di ol  v al u e 
< 4 0   p g/ m L ( 1 4 0  p m ol/ L). 
•   W o m e n  w h o  ar e  > 4 5  y e ars- of- a g e,  usi n g  h or m o n e- r e pl a c e m e nt t h er a p y  a n d  w h o  h a v e 
e x p eri e n c e d t ot al  c ess ati o n  of  m e ns es f or  at l e ast  1  y e ar  O R  w h o  h a v e  h a d  d o c u m e nt e d 
e vi d e n c e  of  m e n o p a us e  b as e d  o n  F S H  > 4 0  mI U/ m L  a n d  estr a di ol  < 4 0  p g/ m L  pri or t o 
i niti ati o n  of  h or m o n e-r e pl a c e m e nt t h er a p y. 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 4  of  6 9  
A p p e n di x  D:  S c h e d ul e  of  Ass ess m e nts    
A S S E S S M E N T S 
B A S E LI N E a 
T R E A T M E N T  
E n d  of  St u d y 
E v al u ati o n  
f or  p ati e nts  wit h 
P D  or 
i nt ol er a bl e 
t o xi citi es 
( wit hi n  3 0  d a ys 
o f tr e at m e nt 
dis c o nti n u ati o n)  
F O L L O W -U P  
I n d u cti o n P h as e  
  (C y cl es r e p e at  e v er y  2 1  d a ys ) 
x   
m a xi m u m  6  c y cl es  
M ai nt e n a n c e  P h as e   
( C y cl es r e p e at  e v er y  2 1 
d a ys) -  
U ntil  P D  or i nt ol er a bl e 
t o xi citi es 
R es p o ns e 
ass ess m e nt   
F o r  p ati e nt s 
dis c o nti n u e d 
p ri o r t o 
di s e as e 
p r o g r essi o n m  
( e v er y  6  w e e ks 
[±  7  D a ys ]) 
A ft e r  dis e as e 
p r o g r essi o n n 
-3 0 
D a ys  
 
-1 4 
D a ys  
C y cl e  1  
D a y  1  
C y cl e  1  
D a y  8  
  
E v e r y  2 1  D a ys  
 
E v e r y  3  
C y cl es   
( ±  7  D a ys) 
 
T ests  a n d  O bs er v ati o ns  
 
 
I nf or m e d  c o ns e nt 
X   
 
 
 
 
 
 
 
 
M e di c al  hist or y   
X   
  
X  
 
X  
 
X  
X  
 
S m o ki n g  hist or y  
X   
 
 
 
 
 
 
 
 
P h ysi c al  e x a m b   ( H ei g ht  o nl y  at first  visit)  
X   
 
X  
 
X  
 
X  
X  
 
Vit al  Si g ns c 
X   
  
X  
 
X  
 
X  
X   
 
E C O G  P S   
X    
  
X  
 
X  
 
 X  
X  
 
1 2 -l e a d E C G  
X   
 
 
  
 
 
 
 
 
A d v er s e  e v e nt  e v al u ati o n  
  
  
X  
 
X  
 
X  
 
 
C o n c o mit a nt  m e di c ati o n r e vi e w  
X   
  
X  
 
X  
 
X  
 
 
L a b or a t or y  O bs er v ati o ns 
 
 
C B C,  3 -p art  diff er e nti al,  a n d  pl at el ets   
  
X   
X a 
X  
X  
 
X  
 
 
C h e mistr y ( C M P) d 
  
X   
X a 
 
X  
 
X  
 
 
P T  or I N R e  
  
X  
 
 
 
 
 
 
 
Uri n e  di psti c k f 
  
X  
 
 
 
 
 
 
 
S er u m  or  Uri n e  Pr e g n a n c y  T est g 
  
X   
X a 
  
X  
 
X  
 
 
St a gi n g  a n d f oll o w  u p  
 
 
C T  S c a n  C h est,  a b d o m e n  a n d  p el vis   
X   
  
 
 
 
X h 
X h, i 
X h  
 
B o n e  S c a n  or  P E T  s c a n j 
( o nl y if  b o n e  m et ast as es  ar e s us p e ct e d)  
X  
 
 
 
 
 
X k 
X k,i 
X k 
 
F oll o w  u p  f or s ur vi v al 
  
 
  
 
 
 
 
 
X  
C orr el ati v e st u di es  
  
 
  
 
 
 
 
 
 
Ar c hi v e d  T u m or  Tiss u e  S a m pl es  
( 1 5 F F P E  sli d es of  5  µ M t hi c k n ess 
s e cti o ns)l 
X  
 
 
 
 
 
 
 
 
Tr e at m e nt  
  
 
  
 
 
 
 
 
 
N a b -p a clit a x el  i nf usi o n 
  
 
X   
X  
X  
 
 
 
 
G e m cit a bi n e  i nf usi o n 
  
 
X   
X  
 
 
 
 
 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 5  of  6 9  
A p p e n di x  D:   S c h e d ul e  of  Ass ess m e nts ( c o nti n u e d)    
 
a   
B as eli n e  bl o o d  c o u nts,  c h e mistri es  a n d  pr e g n a n c y t est  d o  n ot  h a v e t o  b e r e p e at e d  o n  C y cl e  1  D a y  1 if  o bt ai n e d  wit hi n  7 2  h o urs.  
b  
P h ysi c al  e x a mi n ati o n  will i n cl u d e  m e as ur e m e nts  of  h ei g ht ( pr e -tr e at m e nt  visit  o nl y),  w ei g ht.  M e as ur e m e nt  of  w ei g ht is  n ot r e q uir e d f or  visits  o c c urri n g 
aft er  c o m pl eti o n  of tr e at m e nt.     
c  
Vit al si g ns  will i n cl u d e r esti n g  h e art r at e,  bl o o d  pr ess ur e, r es pir at or y r at e,  a n d t e m p er at ur e.  
d  
C M P  will i n cl u d e  m e a s ur e m e nts  of  gl u c os e,  B U N,  cr e ati ni n e, s o di u m,  p ot assi u m,  c hl ori d e,  c al ci u m,  C O 2,  A L P ,  A S T ( S G O T),  A L T ( S G P T), t ot al 
bilir u bi n, t ot al  pr ot ei n,  a n d  al b u mi n .   
e    
If  P T  or I N R  ar e  n or mal  at  b as eli n e t h e y  d o  n ot  n e e d t o  b e r e p e at e d.   P ati e nts r e q uiri n g t h e i niti ati o n  of  a n  a nti -c o a g ul ati o n t h er a p y  d uri n g st u d y 
tr e at m e nt s h o ul d  h a v e  c o a g ul ati o n t ests  p erf or m e d  a c c or di n g t o st a n d ar d  pr a cti c e  g ui d eli n e s. 
f   
Uri n e  di psti c k ( p H,  pr ot ei n,  gl u c os e,  bl o o d,  k et o n es,  a n d l e u k o c yt e s)    
g  
S er u m  or  u ri n e pr e g n a n c y t ests  ar e t o  b e  c o n d u ct e d i n  w o m e n  of  c hil d b e ari n g  p ot e nti al  ( wit hi n  7 2  h o urs  of st u d y tr e at m e nt st art).   
h  
O nl y  C T s c a ns t h at  w er e  a b n or m al  at  b as eli n e  n e e d t o  b e r e p e at e d  at r est a gi n g,  u nl e ss  a d diti o n al  ar e as  ar e  cli ni c all y i n di c at e d.   
i  
O nl y if  P D  n ot  pr e vi o usl y  di a g n os e d  a n d  m ost r e c e nt s c a ns  w er e  d o n e   >  9  w e e ks  pri or   
j  
B o n e s c a ns  or  P E T s c a ns  will  b e  d o n e  3 0  d a ys  pri or t o st art  of tr e at m e nt  i n  p ati e nts  wit h si g ns/s y m pt o ms s us pi ci o us for  b o n e  m et ast a s es .  
k  
If  b as eli n e  b o n e s c a n ( or  P E T s c a n) is  a b n or m al, r e p e at  e v er y 6  c y cl es  ( 1 8  w e e ks)..   
l    
Ar c hi v al t u m or tiss u e s a m pl es fr o m  p ati e nts  ( w h o  h a v e  a n d  c o ns e nt e d t o  pr o vi d e it)s h o ul d  b e  o bt ai n e d  b y st u d y sit e  p ers o n n el f or  c orr el ati v e st u d i e s, 
pr ef er a bl y  pri or t o t h e  e n d  of  C y cl e  1.    
m  
If  p ossi bl e,  p ati e nts  w h o  dis c o nti n u e  st u d y tr e at m e nt  pri or t o  dis e as e  pr o gr essi o n s h o ul d  b e s e e n  e v er y  6  w e e ks ( ±  7  D a ys),  wit h r e-e v al u ati o ns  a s 
i n di c at e d,  u ntil  dis e as e  pr o gr e ssi o n is  d o c u m e nt e d. 
n  
Aft er  dis e as e  pr o gr essi o n,  p ati e nts  will  b e f oll o w e d  e v er y  3  m o nt hs f or s ur vi v al st at us (i. e.  d e at h  d at e  a n d  c a us e  of  d e at h) f or  t h e first  y e ar,  a n d t h e n 
e v er y  6  m o nt hs t h er e aft er  u p t o  5  y e ars.  P ati e nts  m a y  b e  c o nt a ct e d  d uri n g  visits  or  b y t el e p h o n e.  
 
   
  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 6  of  6 9  
A p p e n di x  E:    R es p o ns e  E v al u ati o n  C rit e ri a i n  S oli d  T u m o rs ( R E CI S T)  V e rsi o n  1. 1 
D efi niti o ns  
R es p o ns e  a n d  pr o gr essi o n  will  b e  e v al u at e d i n t his  st u d y usi n g t h e  R e s p o ns e  E v al u ati o n  Crit eri a i n  S oli d  T u m ors 
( R E CI S T)  v ersi o n  1. 1 ( Eis e n ha u er  et  al  2 0 0 9).   L esi o ns  ar e  eit h er  m e a s ur a bl e  or  n o n -m e as ur a bl e  usi n g t h e  crit eri a 
pr o vi d e d  b el o w.   T h e t er m  “ e v al u a bl e ” i n r ef er e n c e t o  m e a s ur a bilit y  will  n ot  b e  us e d,  as it  d o es  n ot  pr o vi d e 
a d diti o n al  m e a ni n g  or  a c c ur a c y.  
B as eli n e  Eli gi bilit y  
M e as u r a b l e  Dis e as e: 
T u m o r  l e si o ns:    M ust  b e  a c c ur at el y    m e a s ur e d  i n  at  l e a st  o n e  di m e nsi o n 
(l o n g est  di a m et er  i n  t h e  pl a n e  of    m e a s ur e m e nt  is  t o  b e  r e c or d e d)    wit h  a 
mi ni m u m si z e  of:  
•   1 0  m m  b y  C T  b y  c o m p ut eri z e d t o m o gr a p h y ( C T  s c a n  sli c e t hi c k n e ss 
n o  gr e at er t h a n  5  m m) . 
•   1 0  m m  c ali p er  m e as ur e m e nt  b y  cli ni c al  e x a m (l e si o ns t h at  c a n n ot  b e 
a c c ur at el y    m e as ur e d    wit h   c ali p ers  s h o ul d   b e  r e c or d e d   as   n o n -
m e as ur a bl e).  
•   2 0  m m  b y  c h e st  x -r a y. 
 
S ki n  l e si o ns:     D o c u m e nt ati o n  b y  c ol or  p h ot o gr a p h y,  i n cl u di n g  a  r ul er  t o 
esti m at e t h e  si z e  of t h e l esi o n, is r e c o m m e n d e d.  
 
M ali g n a nt  l y m p h  n o d e s:     T o  b e  c o nsi d er e d  p at h ol o gi c all y  e nl ar g e d  a n d 
m e as ur a bl e,  a l y m p h  n o d e  m ust  b e  ≥ 1 5  m m i n  s h ort  a xis  w h e n  ass ess e d  b y 
C T  s c a n.   At  b as eli n e  a n d i n f oll o w -u p,  o nl y t h e  s h ort  a xis  will  b e  m e as ur e d 
a n d f oll o w e d.   
N o n -M e as u r a bl e  Dis e as e:  
All   ot h er  l esi o ns,  i n cl u di n g   s m all  l esi o ns  (l o n g est   di a m et er  < < 1 0  m m   or 
p at h ol o gi c al  l y m p h  n o d es   wit h  ≥ 1 0 -  t o < < 1 5 -m m  s h ort  a xis)  as   w ell  as tr ul y 
n o n -m e as ur a bl e  l esi o ns.     L esi o ns  c o nsi d er e d  tr ul y  n o n -m e as ur a bl e  i n cl u d e: 
l e pt o m e ni n g e al  dis e as e,  as cit es,  pl e ur al  or  p eri c ar di al  eff usi o n,  i nfl a m m at or y 
br e ast  dis e as e,  l y m p h a n giti c  i n v ol v e m e nt  of  s ki n  or  l u n g,  a b d o mi n al    m ass es, 
a b d o mi n al  or g a n o m e g al y  i d e ntifi e d  b y  p h ysi c al  e x a m  t h at  is  n ot    m e as ur a bl e 
b y r e pr o d u ci bl e i m a gi n g t e c h ni q u es.   
T a r g et  L esi o ns:  
T h e  m ost r e pr o d u ci bl e  m e a s ur a bl e l esi o ns,  u p t o  a  m a xi m u m  of  2 l esi o ns  p er 
or g a n  a n d  5  l esi o ns i n t ot al,  r e pr es e nt ati v e  of  all i n v ol v e d  or g a ns  s h o ul d  b e 
i d e ntifi e d  as t ar g et l e si o ns  a n d r e c or d e d  a n d  m e a s ur e d  at  b as eli n e.   
T ar g et l esi o ns  s h o ul d  b e  s el e ct e d  o n t h e  b asis  of t h eir  si z e  (l esi o ns  wit h t h e 
l o n g e st  di a m et er),  s h o ul d  b e  r e pr es e nt ati v e  of  all  i n v ol v e d  or g a ns,  a n d  i n 
a d diti o n   s h o ul d   b e  t h os e  t h at  l e n d  t h e ms el v es  t o  r e pr o d u ci bl e  r e p e at e d 
m e as ur e m e nts.   P at h ol o gi c al  n o d es  w hi c h  ar e  d efi n e d  as  m e as ur a bl e  a n d t h at 
m a y  b e i d e ntifi e d  as t ar g et l e si o ns  m ust  m e et t h e  crit eri o n  or  a  s h ort  a xis  of 
≥ 1 5  m m  b y  C T s c a n.  
A  s u m  of t h e  di a m et ers  (l o n g est  f or  n o n -n o d al l esi o ns,  s h ort  a xis  f or  n o d al 
l esi o ns)  f or  all t ar g et l esi o ns  will  b e  c al c ul at e d  a n d  r e p ort e d  as t h e  b as eli n e 
s u m  di a m et ers.  If l y m p h  n o d es  ar e t o  b e i n cl u d e d i n t h e  s u m,  t h e n  as  n ot e d 
a b o v e,  o nl y t h e s h ort  a xis is  a d d e d i nt o t h e  s u m.   T h e  b as eli n e s u m  di a m et ers 
will   b e   us e d   as   r ef er e n c e   t o   f urt h er   c h ar a ct eri z e   a n y   o bj e cti v e   t u m or 
r es p o ns e. 
N o n -T a r g et  L esi o ns:  
All  ot h e r  l esi o ns  s h o ul d  b e  i d e ntifi e d  as  n o n -t a r g et  l esi o ns  at  b as eli n e.  
M e as u r e m e nts  of  t h es e  l esi o ns  a r e  n ot  r e q ui r e d,  b ut  t h e  p r es e n c e  o r 
a bs e n c e  of  e a c h s h o ul d  b e  n ot e d t h r o u g h o ut f oll o w -u p.  


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 7  of  6 9  
G ui d eli n es f o r  E v al u ati o n  of  M e as u r e a bl e  Dis e as e  
All  m e a s ur e m e nts s h o ul d  b e t a k e n  a n d r e c or d e d i n  m etri c  n ot ati o n,  usi n g  a r ul er  or  c ali p ers.   All  b as eli n e 
e v al u ati o ns s h o ul d  b e  p erf or m e d  as  cl os el y  as  p ossi bl e t o t h e  b e gi n ni n g  of tr e at m e nt,  as  p er  pr ot o c ol s cr e e ni n g 
r e q uir e m e nts. 
T h e s a m e  m et h o d  of  ass e ss m e nt  a n d t h e s a m e t e c h ni q u e s h o ul d  b e  us e d t o  c h ar a ct eri z e  e a c h i d e nt ifi e d  a n d r e p ort e d 
l esi o n  at  b as eli n e  a n d  d uri n g f oll o w-u p.  I m a gi n g -b as e d  e v al u ati o n is  pr ef err e d t o  e v al u ati o n  b y  cli ni c al  e x a mi n ati o n 
w h e n  b ot h  m et h o ds  h a v e  b e e n  us e d t o  ass ess t h e  a nti -t u m or  eff e ct  of  a tr e at m e nt. 
 
Cli ni c al  L e si o ns:  
Cli ni c al l esi o ns  wi ll  o nl y  b e  c o nsi d er e d  m e as ur a bl e  w h e n t h e y  ar e s u p erfi ci al 
( e. g.,  s ki n  n o d ul e s  a n d  p al p a bl e l y m p h  n o d es)  a n d  ≥ 1 0  m m i n  di a m et er.   I n 
t h e  c as e  of  s ki n  l esi o ns,  d o c u m e nt ati o n  b y  c ol or  p h ot o gr a p h y,  i n cl u di n g  a 
r ul er t o  esti m at e t h e si z e  of t h e l esi o n, is r e c om m e n d e d.  
C h est  X -r a y:  
L esi o ns  o n  c h e st  X -r a y  ar e  a c c e pt a bl e  as  m e as ur a bl e l esi o ns  w h e n t h e y  ar e 
cl e arl y  d efi n e d  a n d  s urr o u n d e d  b y  a er at e d  l u n g.      H o w e v er,  a    C T  s c a n  is 
pr ef er a bl e.  
C o n v e nti o n al  C T  a n d  M RI:  
C T,  M RI:   C T is t h e  b est  c urr e ntl y  a v ail a bl e  a n d r e pr o d u ci bl e  m et h o d t o 
m e as ur e l esi o ns s el e ct e d f or r es p o ns e  ass ess m e nt.   T his  g ui d eli n e  h a s 
d efi n e d  m e as ur a bilit y  of l esi o ns  o n  C T s c a n  b as e d  o n t h e  ass u m pti o n t h at  C T 
sli c e t hi c k n ess is  5 m m  or l ess.   W h e n  C T s c a ns  h a v e sli c e t hi c k n e ss  gr e at er 
t h a n  5 m m, t h e  mi ni m u m si z e f or  a  m e as ur a bl e l esi o n s h o ul d  b e t wi c e t h e 
sli c e t hi c k n ess.   M RI is  als o  a c c e pt a bl e i n  c ert ai n sit u ati o ns ( e. g. f or  b o d y 
s c a ns).  
Ult r as o u n d:  
W h e n  t h e  pri m ar y  st u d y e n d p oi nt  is  o bj e cti v e  r es p o ns e,  ultr as o u n d  s h o ul d 
n ot  b e  us e d t o  m e as ur e  t u m or l esi o ns.   It is,  h o w e v er,  a  p ossi bl e  alt er n ati v e 
t o  cli ni c al  m e as ur e m e nts  of  s u p erfi ci al  p al p a bl e l y m p h  n o d es,  s u b c ut a n e o us 
l esi o ns,  a n d t h yr oi d  n o d ul es.   Ultr as o u n d  m a y  als o  b e  us ef ul t o  c o nfir m t h e 
c o m pl et e  dis a p p e ar a n c e  of  s u p erfi ci al  l esi o ns  us u a ll y  a ss ess e d  b y  cli ni c al 
e x a mi n ati o n.  
E n d os c o p y  a n d  L a p a r os c o p y:  
Us e  of  e n d os c o p y  a n d l a p ar os c o p y f or  o bj e cti v e t u m or  e v al u ati o n  h a s  n ot  y et 
b e e n  f ull y  a n d    wi d el y  v ali d at e d.      T h er ef or e,  us e  of  t h e s e  t e c h ni q u es  f or 
o bj e cti v e  t u m or  r es p o ns e   s h o ul d   b e  r estri ct e d  t o   v ali d ati o n   p ur p os es  i n 
s p e ci ali z e d  c e nt ers.   S u c h t e c h ni q u es  c a n  b e  us ef ul i n  c o nfir mi n g  c o m pl et e 
p at h ol o gi c al r es p o ns e  w h e n  bi o psi es  ar e  o bt ai n e d.  
T u m o r  M a r k e rs:  
T u m or    m ar k ers  al o n e  c a n n ot  b e  us e d  t o  ass e ss  r es p o ns e.    If    m ar k ers  ar e 
i niti all y  a b o v e t h e  u p p er li mit  of  n or m al, t h e y  m ust  n or m ali z e f or  a s u bj e ct t o 
b e   c o nsi d er e d   i n   c o m pl et e   cli ni c al   r es p o ns e    w h e n   all   l esi o ns   h a v e 
dis a p p e ar e d.  
C yt ol o g y  a n d  Hist ol o g y:  
C yt ol o g y  a n d  hist ol o g y  c a n  b e  us e d t o  diff er e nti at e  b et w e e n  p arti al r es p o ns e 
( P R)  a n d  c o m pl et e  r es p o ns e  ( C R)  i n  r ar e  c as e s  ( e. g.,  aft er  tr e at m e nt  t o 
diff er e nti at e  b et w e e n  r esi d u al  b e ni g n l esi o ns  a n d  r esi d u al   m ali g n a nt l e si o ns 
i n t u m or t y p es  s u c h  as  g er m  c ell t u m or s). 


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 8  of  6 9  
R es p o ns e  C rit e ri a  
E v al u ati o n  of  T a r g et  L esi o ns 
C o m pl et e  R es p o ns e ( C R):   
Dis a p p e ar a n c e  of  all t ar g et l e si o ns.    
P a rti al  R es p o ns e ( P R):   
 
At l e a st  a  3 0 %  d e cr e as e i n t h e s u m  of  di a m et ers  of t ar g et  
l esi o ns, t a ki n g  a s r ef er e n c e t h e  b as eli n e s u m  di a m et ers.. 
St a bl e  Dis e as e ( S D):    
 
N eit h er  s uffi ci e nt  s hri n k a g e  t o   q u alif y  f or   P R   n o r  s uffi ci e nt  i n cr e as e  t o 
q u alif y  f or  P D,  t a ki n g  as  r ef er e n c e  t h e  s m all e st  ( n a dir)  s u m  of  di a m et ers 
si n c e t h e tr e at m e nt  st art e d.  
P r o g r essi v e  Dis e as e ( P D):    
 
At l e a st  a  2 0 % i n cr e as e i n t h e  s u m  of t h e  di a m et ers  of t ar g et l esi o ns, t a ki n g 
as  r ef er e n c e  t h e  s m a ll est  ( n a dir)  s u m  si n c e  t h e  tr e at m e nt  st art e d,   or  t h e 
a p p e ar a n c e  of  o n e  or  m or e  n e w l esi o ns.   R e q uir es  n ot  o nl y  2 0 % i n cr e as e,  b ut 
a bs ol ut e i n cr e a s e  of  a  mi ni m u m  of  5  m m  o v er s u m.  
 
E v al u ati o n  of  N o n -T a r g et  L esi o ns  
C o m pl et e  R es p o ns e ( C R):  
Dis a p p e ar a n c e  of  a ll  n o n-t ar g et l esi o ns  a n d  n or m ali z ati o n  of t u m or  m ar k er s.  
All l y m p h  n o d es  m ust  b e  n o n -p at h ol o gi c al i n si z e ( < < 1 0  m m s h ort  a xis).  
St a bl e  Dis e as e ( S D):     
 
P ersist e n c e  of  o n e  or    m or e  n o n -t ar g et  l esi o ns  a n d/ or  p ersist e n c e  of  t u m or 
m ar k er l e v el  a b o v e t h e  n or m al li mits.  
P r o g r essi v e  Dis e as e ( P D):   
 
A p p e ar a n c e  of  o n e  or    m or e  n e w  l esi o ns  a n d/ or  u n e q ui v o c al  pr o gr essi o n  of 
e xisti n g  n o n -t ar g et l esi o ns.   W h e n t h e s u bj e ct  als o  h as  m e a s ur a bl e  dis e as e, t o 
a c hi e v e  “ u n e q ui v o c al  pr o gr essi o n ”  o n  t h e  b asis  of  t h e  n o n -t ar g et  dis e as e, 
t h er e  m ust  b e  a n  o v er all l e v el  of  s u b st a nti al  w ors e ni n g i n  n o n-t ar g et  dis e as e 
s u c h  t h at,  e v e n  i n  pr es e n c e  of  S D  or  P R  i n  t h e  t ar g et  dis e as e,  t h e  o v er all 
t u m or  b ur d e n  h as i n cr e as e d s uffi ci e ntl y t o  m erit  dis c o nti n u ati o n  of t h er a p y. 
 
E v al u ati o n  of  B est  O v e r all  R es p o ns e  
As  d et a il e d a b o v e, t h e  b est  o v er all r es p o ns e is t h e  b est r es p o ns e r e c or d e d fr o m t h e st art  of t h e tr e at m e nt  u ntil  dis e as e 
pr o gr essi o n/r e c urr e n c e (t a ki n g  as r ef er e n c e f or  P D t h e s m all est  m e a s ur e m e nts r e c or d e d si n c e t h e tr e at m e nt st art e d ).  
I n  g e n er al, t h e s u bj e ct’s  b est r es p o ns e  assi g n m e nt  will  d e p e n d  o n t h e  a c hi e v e m e nt  of  b ot h  m e as ur e m e nt  a n d 
c o nfir m ati o n  crit eri a.    
C o nfir m ati o n  of r es p o ns e ( b y r e p e at s c a ns  aft er  4  w e e ks  or  as s p e cifi e d i n t h e  pr ot o c ol) is r e q uir e d f or  st u di es i n 
w hi c h  r es p o ns e r at e is t h e  pri m ar y  e n d p oi nt,  b ut is  n ot r e q uir e d i n r a n d o mi z e d st u di es or  st u di e s  wit h  pri m ar y 
s ur vi v al  e n d p oi nts (i. e.,  w h er e r es p o ns e is  n ot  a  pri m ar y  e n d p oi nt).


 
C o nfi d e nti al  
S T U D Y  D R U G (S ):  N A B -P A C LI T A X E L  A N D G E M CI T A BI N E       
  
S C RI  IN N O V A TI O N S  S T U D Y  N U M B E R : 
FI N A L  P R O T O C O L  D A T E :  0 2  M A Y  2 0 1 6   
   
   
 
           V E R SI O N   1. 0  
P a g e  6 9  of  6 9  
 
T a r g et  L esi o ns   
N o n -T a r g et  L esi o ns  
N e w  L esi o ns   
O v e r all  R es p o ns e  
C R  
C R  
N O  
C R  
C R  
S D  
N O  
P R  
C R  
N E  
N O  
P R  
P R  
S D  O R  N E  
N O  
P R  
S D  
S D  O R  N E  
N O  
S D  
P D  
A N Y  
Y E S  O R  N O  
P D  
A N Y  
P D  
Y E S  O R  N O  
P D  
A N Y  
A N Y  
Y E S  
P D  
 
I n s o m e  cir c u mst a n c es, it  m a y  b e  diffi c ult t o  disti n g uis h r esi d u al  dis e as e fr o m  n or m al tiss u e.   W h e n t h e  e v al u ati o n 
of  a  C R  d e p e n ds  u p o n  t his  d et er mi n ati o n, it is r e c o m m e n d e d t h at t h e r esi d u al l e si o n  b e i n v esti g at e d  b y fi n e  n e e dl e 
as pir at e  or  bi o ps y t o  c o nfir m t h e  C R st at us.   
W h e n  n o d al  dis e as e is i n cl u d e d i n t h e s u m  of t ar g et l esi o ns,  a n d t h e  n o d es  d e cr e as e t o  “ n or m al ” si z e ( < < 1 0  m m), 
t h ey  m a y still  h a v e  a  m e a s ur e m e nt r e p ort e d  o n s c a ns.   T his  m e as ur e m e nt  s h o ul d  b e r e c or d e d  e v e n t h o u g h t h e  n o d es 
ar e  n or m al i n  or d er  n ot t o  o v erst at e  pr o gr essi o n,  s h o ul d it  b e  b as e d  o n i n cr e as e i n  si z e  of t h e  n o d es.   As  n ot e d 
e arli er, t his  m e a ns t h at  s u bj e cts  wit h  C R  m a y  n ot  h a v e  a t ot al s u m  of  “ z er o ”  o n t h e  e C R F.