Clinical trial: NCT01817751
Section: Confidentiality
Subsections: C O N Fi D E N Ti A Li T Y

R e s e ar c h i nf or m ati o n a b o ut y o u will b e k e pt c o nfi d e nti al t hr o u g h t h e u s e of p a s s w or d pr ot e ct e d el e ctr o ni c fil e s, l o c k e d r e s e ar c h ar e a s, a n d t h e u s e of I D n u m b er s. All p er s o n al i d e ntif yi n g i nf or m ati o n will b e k e pt i n p a s s w or d pr ot e ct e d fil e s. A c c e s s t o all d at a will b e li mit e d t o st u d y p er s o n n el. S a m pl e s u s e d f or r e s e ar c h p ur p o s e s (t h e bi o p s y) will b e st or e d wit h t h e s a m e c o nfi d e nti alit y s af e g u ar d s a s t h e r e s e ar c h i nf or m ati o n. A d at a a n d s af et y m o nit ori n g pl a n i s e st a bli s h e d.  
Y o ur d o ct or will n e e d t o e v al u at e a n ol d bi o p s y o n y o u t o t e st f or t h e pr e s e n c e of c ert ai n pr ot ei n s t h at m a y h el p d et er mi n e w hi c h p ati e nt s ar e b e st tr e at e d wit h t hi s dr u g c o m bi n ati o n. N o n e w r e s e ar c h-r el at e d t e st s ar e r e q uir e d. T h e i nf or m ati o n will b e k e pt c o nfi d e nti al.  
T hi s st u d y d o e s n ot pl a n t o u s e y o ur bi o p s y s a m pl e s t o s e q u e n c e all or p art of y o ur D N A. I n t h e f ut ur e, t h e i d e ntifi er s c o ul d b e r e m o v e d fr o m t h e i nf or m ati o n a n d s a m pl e s y o u pr o vi d e f or t hi s st u d y. Aft er t h at r e m o v al, y o ur i nf or m ati o n a n d s a m pl e s c o ul d b e u s e d f or n e w st u di e s wit h o ut a s ki n g f or y o ur c o n s e nt a g ai n. T h o s e p o s si bl e n e w st u di e s c o ul d b e d o n e b y t hi s st u d y t e a m or ot h er r e s e ar c h er s a n d mi g ht i n v ol v e s e q u e n ci n g all or p art of y o ur D N A. If a n y i n v e nti o n s or di s c o v eri e s r e s ult fr o m t h e u s e of y o ur s a m pl e s, t h er e ar e n o pl a n s t o s h ar e a n y m o n e y or pr ofit s wit h y o u. I n g e n er al, w e will n ot gi v e y o u a n y i n di vi d u al r e s ult s f or t hi s st u d y.  
Y o u s h o ul d k n o w t h at r e s e ar c h i nf or m ati o n a b o ut y o u m a y b e r e vi e w e d or c o pi e d b y t h e s p o n s or of t h e r e s e ar c h or b y Vir gi ni a C o m m o n w e alt h U ni v er sit y. P er s o n al i nf or m ati o n a b o ut y o u mi g ht b e s h ar e d wit h or c o pi e d b y a ut h ori z e d offi ci al s of t h e F e d er al F o o d a n d Dr u g A d mi ni str ati o n, or t h e D e p art m e nt of H e alt h a n d H u m a n S er vi c e s, or ot h er offi ci al a g e n ci e s.  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov , as required by U. S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.  
Although results of this research may be presented at meetings or in publications, identifiable personal information pertaining to participants will not be disclosed.
Clinical trial: NCT01817751
Section: Duration of Study Involvement
Subsections: B Ef Or E Y O U B E Gi N T H E St U D Y:|D Uri N G T H E St U D Y:

Y o u will n e e d t o h a v e t h e f oll o wi n g e x a m s, t e st s or pr o c e d ur e s t o d et er mi n e w h et h er y o u c a n b e i n t h e st u d y:  
A n M RI or c o ntr a st- e n h a n c e d C T s c a n of y o ur br ai n  
Hi st or y a n d p h y si c al e x a mi n ati o n b y y o ur d o ct or A n E C G t o e v al u at e t h e el e ctri c al a cti vit y of y o ur h e art Bl o o d t e st s t o a s s e s s y o ur bl o o d, ki d n e y f u n cti o n, a n d li v er f u n cti o n  
Pr e g n a n c y t e st, if a p pli c a bl e T h e s e e x a m s, t e st s or pr o c e d ur e s ar e p art of r e g ul ar c a n c er c ar e a n d m a y b e d o n e e v e n if y o u d o n ot j oi n t h e st u d y. If y o u h a v e h a d s o m e of t h e m r e c e ntl y, t h e y m a y n ot n e e d t o b e r e p e at e d.  
T hi s will b e u p t o y o ur st u d y d o ct or.

Y o u will t a k e s or af e ni b, v al pr oi c a ci d, a n d sil d e n afil t a bl et s b y m o ut h t wi c e d ail y, o n a n e m pt y st o m a c h. Y o u will k e e p a d ail y dr u g di ar y.  
At e a c h vi sit, y o u s h o ul d bri n g all of y o ur r e m ai ni n g st u d y dr u g s u p pl y t o t h e r e s e ar c h cli ni c.  
Y o u will b e s e e n b y a r e s e ar c h n ur s e a n d/ or d o ct or e v er y 2 w e e k s f or t h e fir st 8 w e e k s - aft er w hi c h y o u will b e s e e n e v er y m o nt h.  
D o ct or s ar e tr yi n g t o l e ar n w hi c h t y p e s of br ai n t u m or s will r e s p o n d t o t hi s tr e at m e nt t h e b e st.  
D o ct or s will a n al y z e y o ur ti s s u e fr o m a pri or bi o p s y t o l o o k f or t h e pr e s e n c e of c ert ai n pr ot ei n s t h at m a y pr e di ct w h o will r e s p o n d t o tr e at m e nt. A n e w r e s e ar c h- o nl y bi o p s y will n ot b e n e e d e d; all t e st s c a n b e p erf or m e d o n ti s s u e t h at h a s alr e a d y b e e n c oll e ct e d.  
M RI or c o ntr a st- e n h a n c e d C T s c a n s will b e p erf or m e d at r e g ul ar i nt er v al s, t o f oll o w t h e st at u s of t h e c a n c er. T hi s h el p s d o ct or s d et er mi n e w h et h er t h e tr e at m e nt i s w or ki n g or n ot. M RI or c o ntr a st- e n h a n c e d C T s c a n s will b e p erf or m e d e v er y 1- 2 m o nt h s, d e p e n di n g o n w h et h er or n ot t h e t u m or a p p e ar s t o b e s hri n ki n g.  
Bl o o d t e st s —t e sti n g y o ur bl o o d, ki d n e y, a n d li v er f u n cti o n - will b e d o n e e v er y ot h er w e e k f or t h e fir st 8 w e e k s a n d t h e n at t h e b e gi n ni n g of e a c h c y cl e.  
E K G s will b e r e p e at e d aft er a b o ut t w o w e e k s a n d ei g ht w e e k s of tr e at m e nt.  
If y o u d e v el o p si d e eff e ct s fr o m t h e tr e at m e nt, pl e a s e t al k wit h y o ur st u d y t e a m or d o ct or a b o ut t h e m. Y o ur d o ct or m a y i n v e sti g at e wit h a d diti o n al t e st s, s u c h a s x-r a y s, C T s, E K G s or bl o o d t e st s. Y o u m a y n e e d a d diti o n al m e di c ati o n s, s u c h a s el e ctr ol yt e s b y m o ut h or i ntr a v e n o u sl y t o m a n a g e si d e eff e ct s. A d diti o n al s p e ci ali st s ( s u c h a s a c ar di ol o gi st) c o ul d b e a s k e d t o c o n s ult o n y o ur sit u ati o n. S o m eti m e s h o s pit ali z ati o n i s r e q uir e d t o m a n a g e si d e eff e ct s or p erf or m a d diti o n al m o nit ori n g. O c c a si o n all y, c ert ai n si d e eff e ct s m a y m a k e it i m p o s si bl e t o c o nti n u e st u d y tr e at m e nt. Y o ur d o ct or or n ur s e will di s c u s s wit h y o u t h e n at ur e of t h o s e t e st s, tr e at m e nt s, a n d d e ci si o n s at t h e ti m e t h e y ar e d et er mi n e d t o b e n e c e s s ar y. Aft er y o u ar e fi ni s h e d wit h t h e st u d y tr e at m e nt w e w o ul d li k e t o st a y i n t o u c h wit h y o u a n d y o ur f a mil y t o s e e h o w y o u ar e d oi n g. W e w o ul d li k e t o k e e p tr a c k of y o ur m e di c al c o n diti o n f or t h e r e st of y o ur lif e. W e w o ul d li k e t o d o t hi s b y c alli n g y o u o n t h e t el e p h o n e o n c e a m o nt h t o s e e h o w y o u ar e d oi n g. K e e pi n g i n t o u c h wit h y o u a n d c h e c ki n g o n y o ur c o n diti o n h el p s u s t o l o o k at t h e l o n g-t er m eff e ct s of t h e st u d y tr e at m e nt.
Clinical trial: NCT01817751
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: W H At Ar E T H E Ri S K S Of T A Ki N G P Art I N T Hi S St U D Y ?|W H At Ar E T H E B E N Efit S Of T A Ki N G P Art I N T Hi S St U D Y ?|Ri S K S A N D Di S C O M F O R T S|B E N E Fi T S T O Y O U A N D O T H E R S|Compensation For Injury Or Illness

W e w a nt t o m a k e s ur e y o u k n o w a b o ut a f e w k e y ri s k s ri g ht n o w. W e gi v e y o u m or e i nf or m ati o n i n t h e " Ri s k s a n d Di s c o mf ort s" s e cti o n.  
T h e c o m bi n ati o n of s or af e ni b, v al pr oi c a ci d, a n d sil d e n afil i s i n v e sti g ati o n al, w hi c h m e a n s t h at it s s af et y a n d eff e cti v e n e s s i s n ot k n o w n. T h e st u d y i s b ei n g c o n d u ct e d b e c a u s e t e st t u b e st u di e s s u g g e st t h at t h e c o m bi n ati o n m a y b e eff e cti v e f or t h e tr e at m e nt of hi g h- gr a d e gli o m a. It i s n ot cl e ar w h et h er t h e c o m bi n ati o n of t h e s e dr u g s will l e a d t o m or e si d e eff e ct s.  
S o m e of t h e m o st c o m m o n si d e eff e ct s t h at t h e st u d y d o ct or s k n o w a b o ut ar e:  
F ati g u e H air t hi n ni n g or p at c h y h air l o s s Di arr h e a N a u s e a L o s s of a p p etit e W ei g ht l o s s Hi g h bl o o d pr e s s ur e R a s h, i n cl u di n g a r e d, bli st eri n g, p ai nf ul r a s h of t h e h a n d s a n d f e et P ai n (i n cl u di n g h e a d a c h e, a b d o m e n, m o ut h, b o n e, a n d t u m or p ai n)  
Tr e m or

T h er e i s n o g u ar a nt e e t h at y o u will r e c ei v e a n y m e di c al b e n efit s fr o m b ei n g i n t hi s st u d y. T h e st u d y dr u g s m a y or m a y n ot b e h el pf ul f or y o ur t y p e of c a n c er. P ati e nt s i n t h e f ut ur e m a y b e n efit fr o m t h e k n o wl e d g e g ai n e d t hr o u g h y o ur p arti ci p ati o n i n t h e st u d y.

Y o ur c o n diti o n m a y n ot g et b ett er or m a y b e c o m e w or s e w hil e y o u ar e i n t hi s st u d y.  
O nl y t h e st u d y p arti ci p a nt s c a n t a k e t h e st u d y dr u g s. T h e y m u st b e k e pt o ut of t h e r e a c h of c hil dr e n a n d p er s o n s w h o m a y n ot b e a bl e t o r e a d or u n d er st a n d t h e l a b el.  
Y o u m a y h a v e s o m e si d e eff e ct s w hil e o n t h e st u d y. Si d e eff e ct s m a y b e mil d or s eri o u s, e v e n p o s si bl y f at al. Y o u m a y b e a s k e d t o t a k e a d diti o n al m e di ci n e s t o pr e v e nt or c o ntr ol si d e eff e ct s.  
S o m e si d e eff e ct s ar e pr e di ct a bl e fr o m p a st e x p eri e n c e wit h s or af e ni b, v al pr oi c a ci d, or sil d e n afil al o n e, b ut ot h er, n e w si d e eff e ct s m a y a p p e ar. M a n y si d e eff e ct s g o a w a y s o o n aft er st o p pi n g st u d y tr e at m e nt, b ut i n s o m e c a s e s si d e eff e ct s m a y n e v er g o a w a y. Y o u s h o ul d t al k t o y o ur st u d y d o ct or a b o ut a n y si d e eff e ct s t h at y o u h a v e w hil e t a ki n g p art i n t h e st u d y.  
```
P o s si bl e si d e eff e ct s a s s o ci at e d wit h t h e u s e of s or af e ni b i n cl u d e:

O c c urri n g i n 1 0 % or m or e of p ati e nt s:

R a s h, i n cl u di n g a r e d, bli st eri n g, p ai nf ul r a s h of t h e h a n d s a n d f e et

R e d n e s s, dr y n e s s, it c hi n g, or p e eli n g of y o ur s ki n

P ai n (i n cl u di n g h e a d a c h e, a b d o m e n, m o ut h, b o n e a n d j oi nt s, a n d t u m or p ai n)

F ati g u e

W e a k n e s s

W ei g ht l o s s

H air t hi n ni n g or p at c h y h air l o s s

N a u s e a

V o miti n g

Di arr h e a

C o n sti p ati o n

Bl e e di n g, i n cl u di n g i nt er n al bl e e di n g

C o n diti o n of t h e n er v o u s s y st e m t h at c a u s e s n u m b n e s s, ti n gli n g, b ur ni n g

L o w w hit e bl o o d c ell s, w hi c h m a y l e a d t o i nf e cti o n

C h e mi c al a b n or m aliti e s of t h e bl o o d (l o w p h o s p h at e, i n cr e a s e d li p a s e, i n cr e a s e d

a m yl a s e)

L o s s of a p p etit e

V oi c e c h a n g e s

C o u g h

I nf e cti o n

S h ort n e s s of br e at h

F e v er

Hi g h bl o o d pr e s s ur e

O c c urri n g i n 1 % t o 1 0 % of p ati e nt s:

A c n e

Fl u s hi n g

F olli c uliti s

T hi c k e ni n g of t h e s ki n, n ail s

S ki n c a n c er ( s q u a m o u s c ell)

I nfl a m m ati o n a n d s or e s of t h e m e m br a n e li ni n g t h e di g e sti v e tr a ct

Dr y or irrit at e d m o ut h a n d t o n g u e

I n di g e sti o n

```  
Diffi c ult y s w all o wi n g T a st e c h a n g e s H e art b ur n Fl u-li k e ill n e s s L o w r e d bl o o d c ell s, w hi c h m a y c a u s e tir e d n e s s or s h ort n e s s of br e at h L o w pl at el et s, w hi c h m a y c a u s e bl e e di n g a n d br ui si n g C h e mi c al a b n or m aliti e s of t h e li v er wit h o ut li v er d y sf u n cti o n L o w bl o o d l e v el s of p ot a s si u m ( p o s si bl e w e a k n e s s)  
L o w bl o o d l e v el s of c al ci u m ( p o s si bl e w e a k n e s s a n d/ or cr a m pi n g).  
L o w bl o o d l e v el s of s o di u m E x c e s s pr ot ei n i n t h e uri n e. T hi s m a y c a u s e fl ui d r et e nti o n M u s cl e p ai n, s p a s m s D e pr e s si o n Er e ctil e d y sf u n cti o n R u n n y n o s e N o s e bl e e d U n d er a cti v e t h yr oi d gl a n d ( p o s si bl e w ei g ht g ai n, h e art f ail ur e, c o n sti p ati o n)  
H e art f ail ur e D e cr e a s e d bl o o d fl o w t o t h e h e art or h e art att a c k (l e s s t h a n 3 % of p ati e nt s)  
Ki d n e y f ail ur e  
```
R ar e b ut s eri o u s ( o c c urri n g i n l e s s t h a n 1 % of p ati e nt s):

S e v er e i n cr e a s e i n bl o o d pr e s s ur e t h at c a n l e a d t o a str o k e

I nfl a m m ati o n of t h e p a n cr e a s or g all bl a d d er

I nt e sti n al d a m a g e, i n cl u di n g f or m ati o n of a l e a k

I nf e cti o n of t h e bil e d u ct

Li v er f ail ur e

P o s si bl e si d e eff e ct s a s s o ci at e d wit h t h e u s e of v al pr oi c a ci d i n cl u d e:

O c c urri n g i n 1 0 % or m or e of p ati e nt s:

H e a d a c h e

W e a k n e s s

N a u s e a

Di arr h e a

V o miti n g

A b d o mi n al p ai n

L o s s of a p p etit e

Tr e m or

Di z zi n e s s

Dr o w si n e s s

D o u bl e vi si o n

L a z y e y e

Bl urr e d vi si o n

Diffi c ult y sl e e pi n g

N er v o u s n e s s

R e s pir at or y i nf e cti o n

I nf e cti o n

```  
L o s s of pl at el et s, w hi c h m a y c a u s e bl e e di n g a n d br ui si n g. Bl e e di n g m a y b e s eri o u s or lif e-t hr e at e ni n g a n d m a y r e q uir e a bl o o d tr a n sf u si o n H air l o s s  
```
O c c urri n g i n 5 % t o 1 0 % of p ati e nt s:

F e v er

C o n sti p ati o n

I n di g e sti o n

Diffi c ult y w al ki n g

M o o d s wi n g s

T hi n ki n g a b n or m al

Br ui si n g

W ei g ht g ai n

W ei g ht l o s s

H air l o s s

R a s h

S w elli n g of t h e ar m s, l e g s

M e m or y c h a n g e s

I n v ol u nt ar y e y e m o v e m e nt

D e pr e s si o n

S or e t hr o at

S h ort n e s s of br e at h

Ri n gi n g i n t h e e ar s

B a c k p ai n

A c ci d e nt al i nj ur y


R ar e b ut s eri o u s ( o c c urri n g i n l e s s t h a n 1 % of p ati e nt s):

I nfl a m m ati o n of t h e p a n cr e a s ( p o s si bl y wit h a b d o mi n al p ai n, bl e e di n g)

Li v er i nj ur y/li v er f ail ur e


P o s si bl e si d e eff e ct s a s s o ci at e d wit h t h e u s e of sil d e n afil i n cl u d e:

Er e cti o n

H e a d a c h e

F a ci al fl u s hi n g

A b n or m al vi si o n, s u c h a s c h a n g e s i n c ol or vi si o n ( s u c h a s h a vi n g a bl u e c ol or ti n g e) a n d

bl urr e d vi si o n.

C h a n g e s i n bl o o d pr e s s ur e ( c a n l o w er bl o o d pr e s s ur e i n s o m e p e o pl e)

I n di g e sti o n

St uff y n o s e

B a c k p ai n

M u s cl e p ai n

N a u s e a

Di z zi n e s s

R a s h

U p s et st o m a c h


```  
R ar el y r e p ort e d si d e eff e ct s a s s o ci at e d wit h sil d e n afil i n cl u d e:  
A n er e cti o n t h at will n ot g o a w a y ( pri a pi s m). If y o u h a v e a n er e cti o n t h at l a st s m or e t h a n 4 h o ur s, g et m e di c al h el p ri g ht a w a y. If it i s n ot tr e at e d ri g ht a w a y, pri a pi s m c a n p er m a n e ntl y d a m a g e y o ur p e ni s.  
S u d d e n vi si o n l o s s i n o n e or b ot h e y e s. S u d d e n vi si o n l o s s i n o n e or b ot h e y e s c a n b e a si g n of a s eri o u s e y e pr o bl e m c all e d n o n- art eriti c a nt eri or i s c h e mi c o pti c n e ur o p at h y  
( N AI O N). St o p t a ki n g sil d e n afil a n d c all y o ur st u d y d o ct or ri g ht a w a y if y o u h a v e s u d d e n vi si o n l o s s i n o n e or b ot h e y e s.  
S u d d e n h e ari n g d e cr e a s e or h e ari n g l o s s. S o m e p e o pl e m a y al s o h a v e ri n gi n g i n t h eir e ar s (ti n nit u s) or di z zi n e s s. If y o u h a v e t h e s e s y m pt o m s, st o p sil d e n afil a n d c o nt a ct y o ur st u d y d o ct or ri g ht a w a y.  
H e art att a c k, str o k e, irr e g ul ar h e art b e at s a n d d e at h h a v e h a p p e n e d r ar el y i n i n di vi d u al s t a ki n g sil d e n afil. M o st, b ut n ot all, of t h e s e i n di vi d u al s h a d h e art pr o bl e m s b ef or e t a ki n g sil d e n afil. It i s n ot k n o w n if sil d e n afil c a u s e d t h e s e pr o bl e m s.  
All er gi c r e a cti o n t o s or af e ni b, v al pr oi c a ci d, or sil d e n afil i s p o s si bl e. S e v er e all er gi c r e a cti o n s c a n b e lif e-t hr e at e ni n g.  
Ot h er, l e s s fr e q u e nt si d e eff e ct s al s o h a v e b e e n r e p ort e d f or t h e s e dr u g s. O n e of t h e s e i n cl u d e s s o m e c h a n g e s t o y o ur h e art tr a ci n g ( E C G) t h at c a n si g n al a s eri o u s pr o bl e m. If y o u n oti c e a n y  
"fl utt eri n g" of y o ur h e art or h e art p al pit ati o n s; if y o u f e el di z z y or cl o s e t o f ai nti n g or " p a s si n g o ut", or if y o u d o f ai nt or p a s s o ut: s e e k e m er g e n c y m e di c al a s si st a n c e, a n d al s o t al k t o y o ur st u d y d o ct or a b o ut t hi s. T al k t o y o ur st u d y d o ct or if y o u w a nt m or e i nf or m ati o n a b o ut t h e s e or ot h er l e s s fr e q u e nt si d e eff e ct s.  
A n ot h er l e s s fr e q u e nt pr o bl e m i s irrit ati o n or i nfl a m m ati o n of t h e p a n cr e a s ( c all e d p a n cr e atiti s).  
If y o u h a v e p ai n i n y o ur a b d o m e n, n a u s e a, v o miti n g, or d e cr e a s e d a p p etit e, t al k t o y o ur st u d y d o ct or. W hil e t h e s e s y m pt o m s c a n o c c ur f or ot h er r e a s o n s, t h e y c a n al s o si g n al p a n cr e atiti s a n d mi g ht r e q uir e pr o m pt m e di c al e v al u ati o n.  
I nt er a cti o n s wit h ot h er m e di c ati o n s: T h er e ar e n u m er o u s m e di c ati o n s t h at c a n i nt er a ct wit h t h e st u d y dr u g s. Y o ur st u d y t e a m will r e vi e w y o ur c urr e nt m e di c ati o n s t o b e s ur e t h at t h er e ar e n o c o n c er n s b ef or e y o u st art t h e st u d y m e di c ati o n s. Y o u s h o ul d n ot st art t a ki n g a n y n e w m e di c ati o n s ( o v er-t h e- c o u nt er or pr e s cri pti o n) wit h o ut fir st c h e c ki n g wit h y o ur st u d y t e a m a b o ut p o s si bl e i nt er a cti o n s. Dr u g i nt er a cti o n s ar e a pr o bl e m b e c a u s e t h e y m a y c a u s e y o u t o h a v e m or e si d e eff e ct s. T h e y m a y al s o l e a d t o d e cr e a s e d eff e cti v e n e s s of m e di c ati o n s. C ert ai n m e di c ati o n s m a y e v e n m a k e it i m p o s si bl e t o c o nti n u e wit h t h e st u d y tr e at m e nt d u e t o t h e i n cr e a s e d ri s k s.  
W e a s k t h at y o u n ot st art a n y n o n- ur g e nt n e w m e di c ati o n s wit h o ut fir st c h e c ki n g wit h y o ur st u d y t e a m a b o ut p o s si bl e i nt er a cti o n s wit h t h e st u d y dr u g. Y o u will al s o b e gi v e n a p o c k et c ar d b y y o ur st u d y t e a m t h at i d e ntifi e s y o ur p arti ci p ati o n i n a cli ni c al tri al. C arr y t hi s wit h y o u at all ti m e s.  
Y o u c a n s h o w it t o a n y pr o vi d er y o u s e e o ut si d e of t h e st u d y t e a m s o t h at t h e y c a n c h e c k wit h a st u d y t e a m m e m b er or d o ct or a b o ut a n y p o s si bl e i nt er a cti o n s t h at m a y o c c ur wit h n e w m e di c ati o n s a d d e d w hil e y o u ar e i n t hi s tri al.  
A st u d y t e a m m e m b er i s a v ail a bl e d uri n g r e g ul ar b u si n e s s h o ur s ( M o n d a y - Fri d a y, 8 a m t o

T h er e i s n o g u ar a nt e e t h at y o u will r e c ei v e a n y m e di c al b e n efit s fr o m b ei n g i n t hi s st u d y. T h e i nf or m ati o n fr o m t hi s r e s e ar c h st u d y m a y l e a d t o a b ett er tr e at m e nt i n t h e f ut ur e f or p e o pl e wit h hi g h- gr a d e gli o m a.

If you are injured by, or become ill, from participating in this study, please contact your study doctor immediately. Medical treatment is available at the Virginia Commonwealth University Health System (VCU Health System). Your study doctor will arrange for short-term emergency care at the VCU Health System or for a referral if it is needed.  
Fees for such treatment may be billed to you or to appropriate third party insurance. Your health insurance company may or may not pay for treatment of injuries or illness as a result of your participation in this study.  
To help avoid research-related injury or illness it is very important to follow all study directions.
Clinical trial: NCT01817751
Section: Procedures
Subsections: W H At Will H A P P E N If I T A K E P Art I N T Hi S St U D Y ?|St U D Y Pl A N

If y o u d e ci d e t o t a k e p art i n t hi s r e s e ar c h st u d y, y o u will b e a s k e d t o si g n t hi s c o n s e nt f or m aft er y o u h a v e h a d all y o ur q u e sti o n s a n s w er e d.  
M o st of t h e e x a m s, t e st s, a n d pr o c e d ur e s y o u will h a v e ar e p art of t h e u s u al a p pr o a c h w h e n tr e ati n g a d v a n c e d c a n c er, if y o u pl a n t o h a v e c a n c er tr e at m e nt. Y o ur st u d y d o ct or or st u d y t e a m will t ell y o u a b o ut t h e s e. T h e r e s ult s of t h e u s u al e x a m s, t e st s, a n d pr o c e d ur e s m a y al s o b e u s e d f or t h e r e s e ar c h p ur p o s e s of t hi s st u d y. W e gi v e y o u m or e i nf or m ati o n i n t h e " Pr o c e d ur e s" s e cti o n.  
All t hr e e dr u g s ( s or af e ni b, v al pr oi c a ci d, a n d sil d e n afil) ar e t a k e n b y m o ut h t wi c e a d a y, e v er y d a y. T h er e i s n o I V c h e m ot h er a p y d uri n g t hi s st u d y. T h er e m a y b e ti m e s w h er e y o ur d o ct or will h a v e y o u n ot t a k e o n e or m or e of t h e t hr e e dr u g s, d e p e n di n g o n si d e eff e ct s. S h o ul d a n y c h a n g e s i n dr u g d o s e s b e c o m e n e c e s s ar y, t hi s will b e c o m m u ni c at e d t o y o u.  
Y o u will r e c ei v e st u d y tr e at m e nt f or a s l o n g a s t h e p o s si bl e b e n efit s o ut w ei g h t h e ri s k s a n d t h e st u d y r e m ai n s o p e n. T hi s i s li k el y t o b e a p eri o d of ti m e m e a s ur e d i n m o nt h s. If t h er e ar e si g nifi c a nt fi n di n g s t h at mi g ht aff e ct y o ur i nt er e st i n p arti ci p ati o n, t h e y will b e s h ar e d wit h y o u.  
U p o n c o m pl eti n g t h e st u d y tr e at m e nt, y o u will b e f oll o w e d f or l at e si d e eff e ct s.

T hi s st u d y pl a n o utli n e s all t e st s a n d e x a m s i n a d diti o n t o t h e a ct u al tr e at m e nt. T h e ti mi n g of s o m e r o uti n e a s s e s s m e nt s m a y v ar y fr o m t h at s h o w n, d e p e n di n g o n y o ur sit u ati o n. F or i n st a n c e, s o m e p arti ci p a nt s will c o nti n u e wit h r e s p o n s e e v al u ati o n aft er tr e at m e nt st o p s, w hil e ot h er s m a y n ot, d e p e n di n g o n t h e st at u s of t h eir c a n c er w h e n tr e at m e nt e n d s.  
| C y cl e 1                                                                                                                                      | C y cl e 2                                                      | Off st u d y tr e at m e nt  f oll o w- u p   |                 |    |    |    |    |    |    |                                |                                  |                           |
|-------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------|-----------------------------------------------|-----------------|----|----|----|----|----|----|--------------------------------|----------------------------------|---------------------------|
| Fir st 8 w e e k s                                                                                                                              |                                                                 |                                               |                 |    |    |    |    |    |    |                                |                                  |                           |
| B ef or e y o u                                                                                                                                 |                                                                 |                                               |                 |    |    |    |    |    |    |                                |                                  |                           |
| T e st                                                                                                                                          | st art st u d y  tr e at m e nt                                 | 1                                             | 2               | 3  | 4  | 5  | 6  | 7  | 8  | M o nt hl y aft er  w e e k 8* | I niti al  3 0- d a y  p eri o d | E xt e n d e d  p eri o d |
| Hi st or y a n d                                                                                                                                | X                                                               | X                                             | X               | X  | X  |    |    |    |    |                                |                                  |                           |
| p h y si c al e x a m  Vit al si g n s,                                                                                                         | X                                                               | X                                             | X               | X  | X  | X  | X  |    |    |                                |                                  |                           |
| w ei g ht Si d e eff e ct s                                                                                                                     | X                                                               | X                                             | X               | X  | X  |    |    |    |    |                                |                                  |                           |
| r e vi e w Dr u g di ar y a n d                                                                                                                 | X                                                               | X                                             | X               | X  |    |    |    |    |    |                                |                                  |                           |
| pill c o u nt R e vi e w of all  ot h er                                                                                                        | X                                                               | X                                             | X               | X  | X  |    |    |    |    |                                |                                  |                           |
| m e di c ati o n s Pr e g n a n c y t e st,  c o u n s eli n g                                                                                  | t h  w e e k of                                                 |                                               |                 |    |    |    |    |    |    |                                |                                  |                           |
| H e art t e st ( E K G)                                                                                                                         | X                                                               | tr e at m e nt                                |                 |    |    |    |    |    |    |                                |                                  |                           |
| R e s p o n s e                                                                                                                                 | E v er y 2 m o nt h s or m or e fr e q u e ntl y if n e e d e d |                                               |                 |    |    |    |    |    |    |                                |                                  |                           |
| e v al u ati o n A n al y si s of pri or  bi o p s y s a m pl e R o uti n e bl o o d                                                            | X                                                               | X                                             | X               | X  | X  |    |    |    |    |                                |                                  |                           |
| t e st s V al pr oi c a ci d                                                                                                                    | X                                                               | X                                             | A s n e e d e d |    |    |    |    |    |    |                                |                                  |                           |
| l e v el M e a s ur e m e nt of  h o w l o n g it t a k e s  f or y o ur bl o o d t o  cl ot (f or  p arti ci p a nt s  t a ki n g w arf ari n) | A s n e e d e d                                                 |                                               |                 |    |    |    |    |    |    |                                |                                  |                           |
| * N ot e: Ti mi n g m a y b e e xt e n d e d f or p arti ci p a nt s w h o r e m ai n o n st u d y f or l o n g er t h a n 3 6 m o nt h s       |                                                                 |                                               |                 |    |    |    |    |    |    |                                |                                  |                           |
Clinical trial: NCT01817751
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

The purpose of this research study is to test the safety, tolerability, and effectiveness of the combination of three drugs, sorafenib (Nexavar®), valproic acid (Depakote®), and sildenafil (Viagra®), when used to treat high-grade glioma, a type of brain tumor. Sorafenib is an anticancer drug approved by the FDA in other types of cancer, but not brain tumors. Valproic acid, available in generic form or a variety of trade names/forms, is used as a standard approach to treating or preventing seizures in patients with high-grade glioma and may enhance the effectiveness of sorafenib in treating cancer. Sildenafil is a medication used for the treatment of erectile dysfunction, and may help with getting sorafenib into the brain tumor. You are being asked to participate in this study because you have been diagnosed with recurrent high-grade approved gli o m a, a n d m a y m e et t h e st u d y e ntr y r e q uir e m e nt s. A p pr o xi m at el y 4 4 i n di vi d u al s will p arti ci p at e i n t hi s st u d y.
Clinical trial: NCT01817751
Section: Voluntary Participation
Subsections: Overview And Key Information Taking Part In This Study Is Your Choice|Voluntary Participation And Withdrawal|C O N S E N T

You can choose to take part or you can choose not to take part in this study. You also can change your mind at any time. Whatever choice you make, you will not lose access to your medical care or give up any legal rights or benefits. If you decide not to enter this study, there are other treatments available. You should talk with your doctor about other possible treatments. You do not have to participate in this study to be treated for high-grade glioma.

Your participation in this study is voluntary. You may decide to not participate in this study. Your decision not to take part will involve no penalty or loss of benefits to which you are otherwise entitled. If you do participate, you may freely withdraw from the study at any time. Your decision to withdraw will involve no penalty or loss of benefits to which you are otherwise entitled. Your participation in this study may be stopped at any time by the study doctor or the sponsor without your consent. The reasons might include: - the study doctor thinks it necessary for your health or safety;
- you have not followed study instructions;
- the sponsor has stopped the study; or - administrative reasons require your withdrawal. If you stop the study treatment, you should follow up with the study team to be checked for side effects.

I h a v e b e e n pr o vi d e d wit h a n o p p ort u nit y t o r e a d t hi s c o n s e nt f or m c ar ef ull y. All of t h e q u e sti o n s t h at I wi s h t o r ai s e c o n c er ni n g t hi s st u d y h a v e b e e n a n s w er e d.  
B y si g ni n g t hi s c o n s e nt f or m, I h a v e n ot w ai v e d a n y of t h e l e g al ri g ht s or b e n efit s, t o w hi c h I  
ot h er wi s e w o ul d b e e ntitl e d. M y si g n at ur e i n di c at e s t h at I fr e el y c o n s e nt t o p arti ci p at e i n t hi s r e s e ar c h st u d y. I will r e c ei v e a c o p y of t h e c o n s e nt f or m o n c e I h a v e a gr e e d t o p arti ci p at e.  
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I n v e sti g at or Si g n at ur e (if diff er e nt fr o m a b o v e) D at e