Conditions: Breastcancer
Keywords: breast cancer paclitaxel
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 28
Healthy volunteers: no

Brief summary:
This is a multicenter, open-label, single-arm PK study in patients for whom paclitaxel treatment is indicated.

Detailed description:
This is a multicenter, open-label, single-arm PK study in approximately 24 breast cancer patients for whom paclitaxel treatment is indicated. The study contains 3 periods: the Screening / Baseline Period, the Treatment Period, and the Follow-up Period. A Final Visit will occur within 7 days of the last dose of study treatment. If subjects achieve stable disease (SD), partial response (PR), or complete response (CR) at the end of the Treatment Period, they may continue Oraxol treatment in a separate extension study.

Arms:
arm 1: Subjects will receive Oraxol 205 mg/m2 daily x 3 days weekly for up to 16 weeks.

Interventions: intervention 1: Oraxol
Intervention descriptions: intervention 1: HM30181 methanesulfonate monohydrate - supplied as 15-mg HM30181AK-US tablets, Paclitaxel - supplied as 30-mg capsules

Protocol document:
Prot_SAP_003.pdf: 
 
Document Title:  
Clinical Study Protocol 
Study Protocol Number: KX-ORAX-007 
Title: A Clinical Study to Determine the Pharmacokinetics of Oraxol in Breast Cancer 
Patients 
 
NCT Number: 03165955 
 
Document Date: 14 August 2018 
 
 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
1 
REVISION HISTORY 
Revisions to KX-ORAX-007 Amendment 05 v6.0_09 Jul 2018 
Current Version and Date:  Amendment 06 v7.0_14 Aug 2018 
Change 
Rationale 
Affected Protocol Sections 
Add a Central Radiology Review 
Committee to review all radiology 
images for activity assessment 
when the patients completed Final 
Visit. 
Further quality assurance of 
efficacy. 
• 
Protocol summary 
- Assessments/Activity 
• 
Section 8.1.2.2  
Add Central Radiology Review for 
response rate to statistical 
analyses. 
To align with collection of Central 
Radiology Review result for tumor 
response. 
• 
Protocol Summary 
- Activity Analyses 
• 
Section 11.5 
 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
2 
 
Revisions to KX-ORAX-007 Amendment 04 v5.0_10 Jul 2017 
Current Version and Date:  Amendment 05 v6.0_09 Jul 2018 
Change 
Rationale 
Affected Protocol Sections 
Added a provision for patients to 
undergo an optional follow-up 
contact every 2 months after the 
study to assess progression-free 
survival, overall survival, and new 
anti-cancer therapy treatment. 
To obtain long-term 
progression-free survival, overall 
survival and new anti-cancer 
therapy data. 
• 
List of Abbreviations 
• 
Protocol Summary 
- Secondary Objectives 
- Secondary Endpoints 
- Study Design 
- Assessments/Activity 
• 
Section 3.2 
• 
Section 3.3.2 
• 
Section 4 
• 
Section 5.3.4 
• 
Section 7.3 
• 
Section 8.1.2.2 
• 
Table 6/footnote b 
Added progression-free survival 
and overall survival to statistical 
analyses. 
To align with collection of long-term 
progression-free survival and 
overall survival data. 
• 
Protocol Summary 
- Activity Analyses 
• 
Section 11.5 
Revised Clinical Pharmacology 
and Biostatistics signatories for the 
Sponsor. 
Administrative. 
• 
Sponsor Signature Page 
 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
3 
 
 
Revisions to KX-ORAX-007 Amendment 03 v4.0_08 May 2017 
Current Version and Date:  Amendment 04 v5.0_10 Jul 2017 
Change 
Rationale 
Affected Protocol Sections 
Revised inclusion for hemoglobin 
from ≥10 g/dL to ≥9 g/dL 
As many patients with cancer may 
have mild anemia, the hemoglobin 
was lowered to 9 g/dL to facilitate 
patient enrollment without 
compromising patient safety. 
• 
Protocol Summary/ 
Inclusion Criteria #5 
• 
Section 5.1/ 
Inclusion Criteria #5 
Added to inclusion criteria GGT 
values (<10 x ULN at Screening) to 
demonstrate adequate liver 
function. 
Preliminary data suggest that 
subjects who receive Oraxol with 
screening GGT ≥10 x ULN may be 
at increased risk for early onset of 
severe neutropenia or serious 
adverse events. 
• 
Protocol Summary/ 
Inclusion Criteria #6 
• 
Section 5.1/ 
Inclusion Criteria #6 
 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
4 
 
Revisions to KX-ORAX-007 Amendment 02 v3.0_08 Jul 2016 
Current Version and Date:   Amendment 03 v4.0_08 May 2017 
Change 
Rationale 
Affected Protocol Sections 
Changed the frequency of 
Hematology testing after Week 4 
from bi-weekly to weekly; adjusted 
volumes of blood samples 
accordingly. 
 
After Week 1, collection of samples 
for laboratory assessments is 
changed from within 72 hours prior 
to dosing to within 48 hours before 
dosing.  Baseline laboratory tests 
and urine pregnancy testing will be 
done within 96 hours before the 
first dose of drug to allow time for 
results to become available prior to 
Week 1 Day 1 dosing. 
 
Changed the visit window for clinic 
visits after Week 4 from ±5 days to 
±2 days. 
To assure that Hematology 
parameters are assessed more 
frequently due to the concern for 
neutropenia. 
 
 
As a consequence of more frequent 
Hematology testing, to assure that 
the most current laboratory results 
are considered for dosing decisions 
each week. 
• 
Section 9.2.3 
• 
Table 6, footnote m 
• 
Table 6 
 
 
 
 
• 
Protocol Summary/ 
Inclusion Criteria #14 
• 
Section 5.1, #14 
• 
Section 9.2.3 
• 
Table 5, footnote b 
• 
Table 6, footnotes f, l, m 
 
 
 
 
 
 
• 
Table 6 
Deleted “If significant bone marrow 
suppression occurs requiring oral 
paclitaxel dose modification or 
withholding treatment, weekly 
hematology tests will be performed 
until drug is restarted and for an 
additional 4 weeks.”  
No longer needed as the frequency 
of hematology testing after Week 4 
has been changed to weekly. 
• 
Section 9.2.3 
• 
Table 6, footnote m 
For subjects receiving Oraxol, the 
definition of an unacceptable 
toxicity was changed from a 
Grade 4 ANC of <0.5x10 9/L to an 
ANC of ≤0.8x109/L, which is not 
Grade 4.  Therefore, any subject 
receiving Oraxol with an ANC 
≤0.8x109/L will have their study 
treatment delayed until the toxicity 
improves to Grade 1 or baseline, 
and then have their dose reduced. 
With weekly dosing of Oraxol, the 
time course of neutropenia 
development may be longer than 
the interdose interval, thus a higher 
threshold for dose unacceptable 
toxicity is proposed. 
• 
Section 6.3.1 
 
 
 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
5 
 
Revisions to KX-ORAX-007 Amendment 02 v3.0_08 Jul 2016 
Current Version and Date:   Amendment 03 v4.0_08 May 2017 
Change 
Rationale 
Affected Protocol Sections 
Inclusion criterion changed to 
restrict the allowed total bilirubin 
level at Screening to ≤1.5 mg/dL in 
all cases.  Previously, subjects 
who had liver metastasis were 
allowed a total bilirubin of ≤2.0 
mg/dL. 
IV paclitaxel usage may have an 
initial dose reduction based on 
initial bilirubin concentration. 
Oraxol is bioequivalent or similar to 
IV paclitaxel. 
• 
Protocol Summary/ 
Inclusion Criteria #6 
• 
Inclusion Criteria #6 
• 
Section 5.1, #6 
Previously, subjects taking Oraxol 
were not allowed any 
premedication before the first 
dose.  Now, for subjects receiving 
Oraxol, anti-emetics should be 
given on each day of Oraxol 
administration, with the first dose 
of anti-emetic given at the same 
time as HM30181. 
Specified that steroids or H-1 
receptor antagonists are not 
allowed as anti-emetics for 
subjects taking Oraxol. 
To improve subject comfort. 
 
 
 
 
 
 
 
Clarification. 
• 
Section 2.3.2 
• 
Section 6.2.3.2 
• 
Section 6.6 
Duration of fasting before and after 
Oraxol dosing is changed from at 
least 8 hours before and 4 hours 
after dosing to at least 6 hours 
before and 2 hours after dosing. 
To facilitate compliance with fasting 
requirements. 
• 
Protocol Summary/ 
Inclusion Criteria #10 
• 
Protocol Summary/ 
Study Treatments 
• 
Section 5.1, #10 
• 
Section 6.2.3.1 
Designated clinic visits on the 
Schedule of Procedures and 
Assessments. 
Clarification. 
• 
Table 6 
Added a ±1 day visit window to the 
Week 4 Day 1 clinic visit. 
Clarification. 
• 
Table 6 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
6 
 
 
Revisions to KX-ORAX-007 Amendment 01 v2.0_03 Apr 2016 
Current Version and Date:   Amendment 02 v3.0_08 Jul 2016 
Change 
Rationale 
Affected Protocol Sections 
Wording describing how long 
subjects may be treated is 
currently as follows:  
Subjects may be treated until 
disease progression, or 
unacceptable toxicity requiring 
more than 2 dose reductions, or a 
maximum of 16 weeks.  
Change from:  Subjects will be 
treated until disease progression, 
or recurrent unacceptable toxicity 
requiring more than 2 dose 
reductions, or a maximum of 
16 weeks. 
Reasons for withdrawal from the 
study include unacceptable 
toxicity; NOT as previously stated:  
recurrent unacceptable toxicity 
requiring more than 2 dose 
reductions.  
Clarification of terms for 
continuation of treatment 
and terms for withdrawal 
from study. 
• 
Protocol Summary/Treatment 
• 
Section 4 
• 
Section 5.3.3 
Added Week 3 to frequency of vital 
signs measurements. 
Correction. 
• 
Section 9.2.6 
Revised text to reflect subjects 
who do not complete Week 4 PK 
assessments will be replaced; 
qualified language about 
replacement of subjects who 
discontinue from the study. 
In response to TFDA 
feedback. 
• 
Protocol Summary/Statistical 
Methods 
• 
Section 5.3.4 
• 
Section 11 
Description of prohibited P-gp 
inhibitors or inducers changed to 
“strong” from “known”. 
Clarification.  
• 
Protocol Summary/Exclusion 
Criteria 
• 
Section 5.2 
• 
Section 6.6 
Restructuring of unacceptable 
toxicity and dose reduction 
sections so that it is clear when 
subjects will be discontinued 
because of unacceptable toxicity 
including when dose reduction will 
occur. 
 
Clarification. 
• 
Protocol Summary/Study 
Treatments 
• 
Section 6.3.1 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
7 
 
Revisions to KX-ORAX-007 Amendment 01 v2.0_03 Apr 2016 
Current Version and Date:   Amendment 02 v3.0_08 Jul 2016 
Change 
Rationale 
Affected Protocol Sections 
With the potential of oral paclitaxel 
dose reduction in this study due to 
unacceptable toxicity, it is noted 
that the dose of HM30181 will 
remain the same. 
Clarification. 
• 
Protocol Summary/Dose 
Reductions 
• 
Section 6.3.1 
Stated that a Pharmacy Manual 
will be provided to the sites with 
dosing and dispensing instructions. 
Clarification. 
• 
Section 6.2.3 
Removal of “IV or sublingual” from 
the description of ondansetron as 
an example of an anti-emetic that 
can be used to manage nausea or 
vomiting following the first dose or 
subsequent doses of Oraxol. 
Clarification. 
• 
Section 6.2.3.2 
Removed timeframe/window 
associated with Oraxol dosing. 
Not needed; clear 
instruction is already 
provided. 
• 
Section 6.5 
Added text that subjects will be 
given information cards on which 
they will record their dosing. 
Clarification. 
• 
Section 6.5 
• 
Table 6, footnote k 
Results of any assessments 
performed at unscheduled visits 
will be entered into the clinical 
database. 
Clarification. 
• 
Section 7.5 
• 
Table 6, footnote c 
Results of unscheduled CT and/or 
MRI scans will be entered into the 
clinical database. 
Clarification. 
• 
Section 8.1.2.1 
• 
Table 6, footnote n 
It is noted that CT and/or MRI 
scans of the chest, abdomen, and 
pelvis should be conducted at 
Baseline and repeated at all 
assessment times to determine the 
possible change in tumor size at 
the respective sites. 
Additional instructions for 
CT and/or MRI are provided 
for clarity. 
• 
Section 8.1.2.1 
Deleted reference to imaging 
acquisition guidelines. 
Not needed; scans will be 
handled according to each 
site’s process. 
• 
Section 8.1.2.1 
Deleted reference to a laboratory 
manual for laboratory parameters. 
Correction; the laboratory 
manual is for PK samples 
only. 
• 
Section 8.2.1 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
8 
 
Revisions to KX-ORAX-007 Amendment 01 v2.0_03 Apr 2016 
Current Version and Date:   Amendment 02 v3.0_08 Jul 2016 
Change 
Rationale 
Affected Protocol Sections 
Specified that AEs will be 
assessed and recorded at all clinic 
visits, and that subjects will be 
instructed to call study personnel if 
they experience AEs in between 
clinic visits. 
Clarification. 
• 
Section 9.2.1 
• 
Table 6, footnote p 
The hematology assessments are 
weekly assessments for the first 
4 weeks of treatment (change is 
the addition of an assessment at 
Week 3 to the previously 
designated assessments at 
Weeks 1, 2, & 4). 
After Week 4, hematology testing 
will be performed every other 
week.  If significant bone marrow 
suppression occurs requiring oral 
paclitaxel dose modification or 
withholding treatment, weekly 
hematology tests will be performed 
until drug is restarted and for an 
additional 4 weeks. 
Any additional hematology tests 
may be done at the discretion of 
the Investigator.  All hematology 
data obtained on subjects during 
this study will be included in the 
clinical database. 
Additional hematology 
assessments according to 
standard safety practices 
including additional tests if 
there is bone marrow 
suppression after Oraxol 
treatment. 
 
 
 
 
 
 
 
Clarification of procedures 
for additional hematology 
testing and for the data 
obtained. 
• 
Section 9.2.3 
• 
Table 6, footnote m 
Urinalysis will be conducted at 
Screening/Baseline and within 
72 hours prior to Day 1 dosing at 
Weeks 1, 4, 8, 12, and 16 instead 
of at Day 1 of every week up to 
Week 16 as previously stated. 
Microscopic urinalysis will be 
conducted only when clinically 
indicated based on dipstick results 
(laboratory protocol) or as 
determined by the Investigator, not 
for all urinalyses as previously 
stated. 
Change in frequency of 
urinalysis testing necessary 
for safety analysis. 
 
 
 
Correction of stated 
procedures. 
• 
Section 9.2.3 
• 
Table 5, footnote c 
• 
Table 6, footnote l 
Notation that depending on 
laboratory certain hematological 
parameters may not be collected.  
Clarification. 
• 
Table 5, footnote a 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
9 
 
Revisions to KX-ORAX-007 Amendment 01 v2.0_03 Apr 2016 
Current Version and Date:   Amendment 02 v3.0_08 Jul 2016 
Change 
Rationale 
Affected Protocol Sections 
Revised description of timing of 
ECGs. 
Clarification. 
• 
Section 9.2.5 
Specified that concomitant 
medications will be assessed and 
recorded at all clinic visits, and that 
subjects will be instructed to call 
study personnel with any AEs they 
experience in between clinic visits, 
as well as any associated 
concomitant medications. 
Clarification. 
• 
Section 9.2.8 
• 
Table 6, footnote e 
Standard safety language was 
added for reporting of a pregnancy 
and subject withdrawal due to 
pregnancy. 
Clarification. 
• 
Section 9.3.3.3 
The safety follow-up procedures 
have been clarified to the following:  
Subjects with onset of study drug-
related AEs will be followed until 
resolution, resolved with sequelae, 
or under medical care.  Previously 
the following was stated:  
Treatment -emergent AEs will be 
followed through the last subject 
contact. 
Clarification. 
• 
Section 9.4 
On the schedule, revised footnote 
for adverse events to reflect that 
AEs will be collected from the time 
the informed consent is signed. 
Clarification 
• 
Table 6, footnote p 
The Table of Procedures and 
Assessments was changed to 
reflect the above changes.  Clinic 
visit days are noted on the table. 
Clarification. 
• 
Table 6 
Minor formatting, section 
organization, and editorial changes 
were made. 
Changed for consistency. 
• 
Throughout document 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
10 
 
Revisions to KX-ORAX-007 protocol v1.0_20 Jan 2016 (original protocol) 
Current Version and Date:  v2.0_03 Apr 2016 
Change 
Rationale 
Affected Protocol Sections 
Revised PK sampling timepoints. 
The 1-hr PK sampling 
timepoint was added to 
cover the Oraxol Tmax 1~1.5 
hr observed in a previous 
study. 
The 3-hr PK sampling 
timepoint was added to 
support PK modeling. 
• 
Protocol 
Summary/Pharmacokinetic 
• 
Section 8.2 
• 
Table 2 
• 
Table 3 
• 
Table 4 
Revised text describing the study 
period. 
The study period duration 
of 8 months is unchanged 
from original protocol. The 
planned clinical study start 
and end dates were 
removed because the 
protocol is pending TFDA 
approval. 
• 
Protocol Summary/Study Period 
• 
Section 4 
Reorganized information in 
protocol summary. 
Clarification. 
• 
Protocol Summary 
Revised text to say all 24 subjects 
will undergo PK sampling in Week 
4, instead of the first 12 subjects. 
To provide additional PK 
information regarding 
Oraxol chronic dosing.  
• 
Protocol 
Summary/Pharmacokinetic 
• 
Section 4 
• 
Section 7.2 
• 
Section 8.2 
• 
Table 2 
• 
Table 3 
• 
Table 4 
• 
Table 6 
Revised text to say that in addition 
to those who achieve stable 
disease or partial response, 
subjects who achieve complete 
response may also continue 
treatment in an extension study. 
Complete responders 
should be offered the option 
of continued Oraxol 
treatment for the same 
reasons it is offered to 
those with stable disease or 
partial response. 
• 
Protocol Summary/Study Design 
• 
Section 4 
Added a co-Sponsor for the study. 
PharmaEssentia is the local 
Sponsor for KX-ORAX-007 
in Taiwan. 
• 
Title Page 
• 
Protocol Summary (added 
Sponsors) 
• 
Section 1 
Revised description of study 
treatments. 
Clarification. 
• 
Protocol Summary/Study 
Treatments 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
11 
 
Revisions to KX-ORAX-007 protocol v1.0_20 Jan 2016 (original protocol) 
Current Version and Date:  v2.0_03 Apr 2016 
Change 
Rationale 
Affected Protocol Sections 
Revised background information. 
Clarification. 
• 
Protocol Summary/Background 
• 
Section 2.1 
Added information regarding dose 
reductions. 
Clarification (previously was 
in Section 6.3.1, but not in 
the Protocol Summary). 
• 
Protocol Summary/Study 
Treatments 
Stipulated that subjects who do not 
have Week 4 PK assessments will 
not be replaced; specified the 
number of evaluable subjects for 
analysis. 
Clarification. 
• 
Protocol Summary/Statistical 
Methods 
• 
Section 11 
Added a 10-minute window to PK 
sampling times; provided 
instructions regarding collection 
times for all PK samples. 
Clarification. 
• 
Section 8.2 
• 
Table 3 
• 
Table 4 
Revised text pertaining to gastric 
cancer diagnosis in oncology 
history. 
Correction (study is in 
breast cancer patients). 
• 
Section 8.1.1.3 
Indicated pregnancy testing on 
Week 1, Day 1 of the schedule of 
assessments. 
Correction. 
• 
Table 6 
 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
12 
 
 
 
Clinical Study Protocol 
 
Study Protocol 
Title: 
A Clinical Study to Determine the Pharmacokinetics of Oraxol in Breast 
Cancer Patients 
 
 
Study Protocol 
Number: 
KX-ORAX-007 
 
 
UTN: 
U1111-1176-4228 
 
 
Investigational 
Product Name: 
Oraxol (Oral paclitaxel + HM30181AK-US) 
 
 
Sponsor: 
Kinex Pharmaceuticals, Inc. 
20 Commerce Drive 
Cranford, New Jersey 07016 USA 
Tel: (908) 272-0628 
PharmaEssentia Inc. 
13F, No. 3, YuanQu Street 
NanKang District, Taipei 115, 
Taiwan (Nangang Software Park) 
Tel: +886-2-2655-7688 
 
 
Principal 
Investigator: 
Tsu-Yi Chao MD, DMS, PhD 
Taipei Medical University Shuang Ho Hospital 
No.291, Zhongzheng Road 
Zhonghe District  
New Taipei City, 23561, Taiwan 
+886227361661 ext 3229  
 
 
Approval Date:  
v1.0 
v2.0  
v3.0 
v4.0 
v5.0 
v6.0 
v7.0 
20 January 2016 FINAL (original protocol) 
03 April 2016 FINAL (Amendment 01)  
08 July 2016  FINAL (Amendment 02) 
08 May 2017  FINAL (Amendment 03) 
10 Jul 2017    FINAL  (Amendment 04) 
09 Jul 2018    FINAL  (Amendment 05) 
14 Aug 2018  FINAL  (Amendment 06) 
 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
13 
 
STATEMENT OF COMPLIANCE 
This study is to be performed in full compliance with International Conference on Harmonisation 
of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and all 
applicable local Good Clinical Practice (GCP) and regulations.  All required study documentation 
will be archived as required by regulatory authorities. 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
SIGNATURE PAGES 
SPONSOR 
Study Protocol Number: 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
Study Protocol Title: 
A Clinical Study to Determine the Pharmacokinetics of Oraxol in 
Breast Cancer Patients 
lnvestigational Product 
Oraxol (Oral paclitaxel + HM30181AK-US) 
Name: 
UTN Number: 
U 1111-1176-4228 
SIGNATURES 
David Cutler, MD, FRCP(C) 
Study Director 
Kinex Pharmaceuticals, Inc. 
Alissa Verone-Boyle, PhD 
Scientist, Clinical Pharmacology 
Kinex Pharmaceuticals, Inc. 
Cynthia Chang, MS 
Biostatistician 
Kinex Pharmaceuticals, Inc. 
Date 
Date 
Date 
14 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
SIGNATURE PAGES 
SPONSOR 
Study Protocol Number: KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
Study Protocol Title: 
A Clinical Study to Determine the Pharmacokinetics of Oraxol in 
Breast Cancer Patients 
lnvestigational Product 
Oraxol (Oral paclitaxel + HM30181AK-US) 
Name: 
UTN Number: 
U 1111-1176-4228 
SIGNATURES 
David Cutler, MD, FRCP(C) 
Study Director 
Kinex Pharmaceuticals, Inc. 
sA~e, PhD 
Scientist, Clinical Pharmacology 
Kinex Pharmaceuticals, Inc. 
Cynthia Chang, MS 
Biostatistician 
Kinex Pharmaceuticals, Inc. 
Date 
IY ~Uf:::l 7..1!> 'co 
Date 
Date 
14 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
SIGNATURE PAGES 
SPONSOR 
Study Protocol Number: 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
Study Protocol Title: 
A Clinical Study to Determine the Pharmacokinetics of Oraxol in 
Breast Cancer Patients 
lnvestigational Product 
Oraxol (Oral paclitaxel + HM30181AK-US) 
Name: 
UTN Number: 
U1111-1176-4228 
SIGNATURES 
David Cutler, MD, FRCP(C) 
Study Director 
Kinex Pharmaceuticals, Inc. 
Alissa Verone-Boyle, PhD 
Scientist, Clinical Pharmacology 
Kinex Pharmaceuticals, Inc. 
" 
Cynthia Chang, MSJ 
Biostatistician 
Kinex Pharmaceuticals, Inc. 
Date 
Date 
14 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
15 
 
INVESTIGATOR 
Study Protocol Number: KX-ORAX-007 
Study Protocol Title: 
A Clinical Study to Determine the Pharmacokinetics of Oraxol in 
Breast Cancer Patients 
Investigational Product 
Name: 
Oraxol (Oral paclitaxel + HM30181AK-US) 
UTN Number: 
U1111-1176-4228 
 
I have read this protocol and agree to conduct this study in accordance with all stipulations of the 
protocol and in accordance with International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH) and all applicable local 
Good Clinical Practice (GCP) guidelines, including the Declaration of Helsinki. 
 
 
 
<Name of institution> 
Medical Institution 
 
<Name, degree(s)> 
  
  
Investigator 
 Signature 
 Date 
 
 
 
 
 


Clinical Study Protocol_Amendment 06 
KX-ORAX-007 
Final (Version 7.0) 
14 Aug 2018 
 
 
page 
16 
TABLE OF CONTENTS 
REVISION HISTORY .................................................................................................................. 1 
STATEMENT OF COMPLIANCE .............................................................................................. 13 
SIGNATURE PAGES ................................................................................................................ 14 
TABLE OF CONTENTS ............................................................................................................ 16 
LIST OF ABBREVIATIONS ....................................................................................................... 19 
PROTOCOL SUMMARY ........................................................................................................... 21 
 
Key Roles ......................................................................................................................... 28 
 
Background Information and Scientific Rationale.............................................................. 29 
 
Background Information ........................................................................................ 29 
 
Rationale .............................................................................................................. 32 
 
Potential Risks and Benefits ................................................................................. 33 
 
Potential Risks .......................................................................................... 33 
 
Known Potential Benefits........................................................................... 33 
 
Objectives ........................................................................................................................ 34 
 
Primary Study Objective ....................................................................................... 34 
 
Secondary Study Objectives ................................................................................. 34 
 
Study Outcome Measures .................................................................................... 34 
 
Primary Outcome Measures ...................................................................... 34 
 
Secondary Outcome Measures ................................................................. 34 
 
Study Design .................................................................................................................... 35 
 
Study Enrollment and Withdrawal ..................................................................................... 36 
 
Subject Inclusion Criteria ...................................................................................... 36 
 
Subject Exclusion Criteria ..................................................................................... 37 
 
Treatment Assignment Procedures ....................................................................... 38 
 
Randomization Procedures ....................................................................... 38 
 
Masking Procedures .................................................................................. 38 
 
Reasons for Withdrawal ............................................................................ 38 
 
Handling of Withdrawals ............................................................................ 39 
 
Termination of Study ................................................................................. 39 
 
Study Intervention/Investigational Product ........................................................................ 41 
 
Study Product Description .................................................................................... 41 
 
Formulation, Packaging, and Labeling....................................................... 41 
 
Product Storage and Stability .................................................................... 43 
 
Dosage, Preparation and Administration of Study Intervention/Investigational 
Product ................................................................................................................. 43 
 
Description and Justification of Dosage Regimen ...................................... 43 
 
Treatments Administered .......................................................................... 43 
 
Dosing Administration of Study Drugs ....................................................... 44 
 
Modification of Study Intervention/Investigational Product for a Subject ................ 45 
 
Unacceptable Toxicity, Dose Interruption, and Dose Reduction ................ 45 


Clinical Study Protocol_Amendment 06 
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17 
 
 
Accountability Procedures for the Study Intervention/Investigational Products ...... 46 
 
Assessment of Subject Compliance with Study Intervention / Investigational 
Product ................................................................................................................. 48 
 
Concomitant Medications/Treatments ................................................................... 48 
 
Study Schedule ................................................................................................................ 50 
 
Screening / Baseline ............................................................................................. 50 
 
Treatment ............................................................................................................. 50 
 
Follow-up .............................................................................................................. 50 
 
Early Termination Visit .......................................................................................... 51 
 
Unscheduled Visit ................................................................................................. 51 
 
Study Procedures/Evaluations .......................................................................................... 52 
 
Clinical Evaluations ............................................................................................... 52 
 
Screening/Baseline Assessments ............................................................. 52 
 
Assessment of Activity .............................................................................. 53 
 
Pharmacokinetics ................................................................................................. 54 
 
Specimen Preparation, Handling, and Shipping ........................................ 56 
 
Assessment of Safety ....................................................................................................... 57 
 
Specification of Safety Parameters ....................................................................... 57 
 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters
 ............................................................................................................................. 57 
 
Adverse Events ......................................................................................... 57 
 
Serious AEs and Other Events of Interest ................................................. 59 
 
Laboratory Evaluations .............................................................................. 60 
 
Procedures to be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings ........................................................ 63 
 
Electrocardiograms ................................................................................... 64 
 
Vital Signs ................................................................................................. 64 
 
Physical Examinations .............................................................................. 64 
 
Concomitant Medications .......................................................................... 64 
 
Reporting Procedures ........................................................................................... 64 
 
Serious Adverse Events ............................................................................ 65 
 
Regulatory Reporting ................................................................................ 65 
 
Other Adverse Events ............................................................................... 65 
 
Type and Duration of Follow-up of Subjects after Adverse Events ........................ 67 
 
Clinical Monitoring ............................................................................................................ 68 
 
Site Monitoring Plan .............................................................................................. 68 
 
Statistical Considerations ................................................................................................. 69 
 
Study Hypotheses ................................................................................................. 69 
 
Planned Interim Analyses ..................................................................................... 69 
 
Pharmacokinetic Analyses .................................................................................... 70 
 Calculation of Noncompartmental Pharmacokinetic Parameters ............... 70 
11.3.2 Population Pharmacokinetic Analysis ........................................................ 70 


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Safety Analyses .................................................................................................... 70 
 Extent of Exposure .................................................................................... 70 
 Adverse Events ......................................................................................... 70 
 Laboratory Values ..................................................................................... 71 
 Vital Signs ................................................................................................. 71 
 Other Special Tests ................................................................................... 71 
 
Activity Analyses ................................................................................................... 72 
 
Final Analysis Plan ............................................................................................... 72 
 
Source Documents and Access to Source Data/Documents ............................................ 73 
 
Quality Control and Quality Assurance ............................................................................. 74 
 
Auditing Procedures and Inspection ...................................................................... 74 
 
Database Quality Assurance ................................................................................. 74 
 
Ethics/Protection of Human Subjects ................................................................................ 75 
 
Ethical Standard ................................................................................................... 75 
 
Institutional Review Board/Independent Ethics Committee ................................... 75 
 
Informed Consent Process ................................................................................... 75 
 
Subject Confidentiality .......................................................................................... 75 
 
Future Use of Stored Specimens .......................................................................... 76 
 
Subject Insurance and Indemnity .......................................................................... 76 
 
Data Handling and Record Keeping ................................................................................. 77 
 
Data Management Responsibilities ....................................................................... 77 
 
Data Capture Methods .......................................................................................... 77 
 
Types of Data ....................................................................................................... 77 
 
Study Records Retention ...................................................................................... 78 
 
Protocol Deviations ............................................................................................... 78 
 
Publication Policy ............................................................................................................. 79 
 
Literature References ....................................................................................................... 80 
Supplements/Appendices ......................................................................................................... 81 
Appendix A:  Schedule of Events .............................................................................................. 82 
Appendix B:  ECOG Performance Status .................................................................................. 85 
Appendix C:  RECIST CRITERIA .............................................................................................. 86 
 
 


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19 
LIST OF ABBREVIATIONS 
Abbreviation 
Terms 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC0-∞ 
area under the curve extrapolated to infinity  
BSA 
body surface area 
CI 
confidence interval  
Cmax 
maximum observed concentration  
CNS 
central nervous system 
CR 
complete response 
CRA 
contract research associate 
CRO 
contract research organization 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration (US) 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HEENT 
head, eyes, ears, nose, and throat 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation ( of Technical 
Requirements for Registration of Pharmaceuticals for Human 
Use) 
IEC 
Independent Ethics Committee 
IP 
investigational product 


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Abbreviation 
Terms 
IRB 
Institutional Review Board  
IV 
intravenous(ly) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTD 
maximum tolerated dose 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 
OS 
overall survival 
PFS 
progression-free survival 
P-gp 
P-glycoprotein 
PK 
pharmacokinetics 
PR 
partial response 
PT 
preferred term 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SOC 
System Organ Class 
SOP 
standard operating procedure 
TEAE 
treatment-emergent adverse event 
TNM 
Tumor, Node, Metastases (Classification of Malignant Tumours) 
ULN 
upper limit of normal 
 


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PROTOCOL SUMMARY 
Sponsors 
Kinex Pharmaceuticals, Inc., USA and PharmaEssentia, Inc., Taiwan 
Study Number 
KX-ORAX-007 
Name of Active Ingredient 
Paclitaxel: 
5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13- ester with 
(2R,3S)-N-benzoyl-3-phenylisoserine 
HM30181 methanesulfonate monohydrate:  
N-(2-(2-(4-(2-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-2H-tetrazol-5-yl)-4,5-
dimethoxyphenyl)-4-oxo-4H-chromene-2-carboxamide Methanesulfonate monohydrate 
Title of Study 
A Clinical Study to Determine the Pharmacokinetics of Oraxol in Breast Cancer Patients  
Phase of Development 
This is a pharmacokinetic (PK) study. 
Study Sites 
Approximately 6 sites in Taiwan 
Background 
Intravenous (IV) paclitaxel is an approved treatment for breast cancer.  Paclitaxel 80 mg/m2 weekly is 
the most commonly used regimen for treatment of breast cancer patients.  Effective blood concentrations 
of paclitaxel and duration (AUC) can predict clinical outcomes. 
Oraxol is an oral dosage form of the chemotherapeutic agent paclitaxel administered with a novel 
P-glycoprotein (P-gp) inhibitor, HM30181, to enhance the oral absorption of paclitaxel in cancer patients. 
Phase1 and 2 clinical studies with HM30181A and oral paclitaxel (Oraxol) in 111 oncology patients 
showed that Oraxol was well tolerated.  The MTD was not reached, and no anaphylactic reactions were 
observed.  Premedication was not required for Oraxol treatment.  The overall safety profile of oral 
paclitaxel may be better than IV paclitaxel.  A Phase 2 clinical trial showed encouraging survival efficacy 
data in the treatment of gastric cancer.  
A clinical PK study showed that HM30181 15 mg plus oral paclitaxel 205 mg/m2 administered for 
3 consecutive days per week can produce a paclitaxel exposure (AUC) similar to that of 80 mg/m2 IV 
paclitaxel per week in cancer patients. 
Objectives 
Primary Objective: 
• 
To investigate the PK (AUC) of orally administered paclitaxel (as Oraxol) in breast cancer 
patients 
 
 


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Secondary Objectives: 
• 
To determine the safety and activity (response rate, progression-free survival [PFS], overall 
survival [OS]) of Oraxol in breast cancer patients 
Endpoints: 
Primary Endpoint: 
• 
Evaluation of PK parameters for oral paclitaxel  
Secondary Endpoints: 
• 
Safety 
- Incidence of all AEs, including SAEs 
- Laboratory values 
- Other safety assessments including vital signs, physical exams, electrocardiograms (ECGs) 
• 
Activity 
- Tumor response rate, which is defined as the number of subjects with complete response (CR) 
or partial response (PR) at any post-baseline assessments expressed as the proportion of the 
total number of subjects in the Full Analysis Set 
- PFS and OS 
Study Design 
This is a multicenter, open-label, single-arm PK study in approximately 24 breast cancer patients for 
whom paclitaxel treatment is indicated.  Subjects must have measurable disease as per RECIST v1.1 
criteria.  The study contains 3 periods:  the Screening / Baseline Period, the 16-week Treatment Period, 
and the 1-week Follow-up Period.  A Final Visit will occur within 7 days of the last dose of study treatment.  
After completion of Final Visit assessments, subjects will be contacted every 2 months to follow 
progression-free survival and overall survival. New anti-cancer therapy will be collected. 
If subjects achieve stable disease (SD), partial response (PR), or complete response (CR) at Week 16, 
they may continue Oraxol treatment in a separate extension study.  The schedule of assessments is 
presented in Appendix A. 
Treatment 
Subjects will receive Oraxol 205 mg/m2 daily x 3 days weekly for up to 16 weeks.  Subjects may be 
treated until disease progression, or unacceptable toxicity requiring more than 2 dose reductions, or a 
maximum of 16 weeks. 
Study Period 
Approximately 8 months (first person first visit to last person last visit [FPFV-LPLV]); approximately 
21 weeks for each subject (4 weeks Screening/Baseline; 16 weeks for treatment; 1 week follow-up). 
Inclusion Criteria 
Subjects must meet all of the following criteria to be included in this study: 
1. Signed written informed consent 
2. Women ≥18 years of age on day of consent 
3. Breast cancer in patients for whom treatment with IV paclitaxel at 80 mg/m2 as monotherapy has 
been recommended by their oncologist  


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4. Measurable disease as per RECIST v1.1 criteria 
5. Adequate hematological status as demonstrated by not requiring transfusion support or 
granulocyte-colony stimulating factor (G-CSF) to maintain: 
• 
Absolute neutrophil count (ANC) ≥1.5 x 109/L 
• 
Platelet count ≥100 x 109/L 
• 
Hemoglobin (Hgb) ≥9 g/dL 
6. Adequate liver function as demonstrated by: 
• 
Total bilirubin of ≤1.5 mg/dL 
• 
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of 
normal (ULN) or ≤5 x ULN if liver metastasis is present 
• 
Alkaline phosphatase (ALP) ≤3 x ULN or ≤5 x ULN if bone metastasis is present 
• 
Gamma glutamyl transferase (GGT) <10 x ULN  
7. Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN 
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
9. Life expectancy of at least 3 months 
10. Willing to fast for 6 hours before and 2 hours after Oraxol administration on all treatment days 
11. Willing to abstain from alcohol consumption for 3 days before the first dose of study drug through 
the completion of the second inpatient PK sampling period 
12. Willing to refrain from caffeine consumption for 12 hours before each inpatient dosing period 
(Weeks 1 and 4) through the completion of protocol-specified PK sampling for that week 
13. Subjects must be postmenopausal (>12 months without menses) or surgically sterile (ie, by 
hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie, oral 
contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree 
to continue use of contraception for 30 days after their last dose of assigned study treatment. 
14. Subjects who are of childbearing potential must have a negative serum pregnancy test at 
Screening and within 96 hours before Week 1 dosing. 


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Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from this study: 
1. Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous 
investigational products (IPs) 
2. If previously treated with a taxane (paclitaxel or docetaxel) as part of anthracycline-based 
adjuvant chemotherapy or for metastatic disease, the subject relapsed less than 1 year following 
treatment 
3. Subjects unable to swallow study medication in its intact form or have clinically significant 
malabsorption syndrome 
4. Only site of metastatic disease is unmeasurable according to RECIST v1.1 criteria 
5. Known CNS metastasis, including leptomeningeal involvement 
6. Received IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer 
7. Are currently receiving other medications intended for the treatment of their malignancy 
8. Women who are pregnant or breastfeeding 
9. Taking any of the following prohibited medications: 
• 
Strong inhibitors (eg, ketoconazole) or inducers (eg, rifampin or St. John's Wort) of CYP3A4 
(within 2 weeks prior to the start of dosing in the study) 
• 
Strong inhibitors (eg, gemfibrozil) or inducers (eg, rifampin) of CYP2C8 (within 2 weeks prior 
to the start of dosing in the study) 
• 
Strong P-gp inhibitors or inducers.  Subjects who are taking such medications but who are 
otherwise eligible may be enrolled if they discontinue the medication ≥1 week before dosing 
and remain off that medication through the end of study treatment. 
• 
An oral medication with a narrow therapeutic index known to be a P-gp substrate (eg, 
digoxin, dabigatran) within 24 hours prior to start of dosing in the study 
10. Use of warfarin.  Subjects receiving warfarin who are otherwise eligible and who may be 
appropriately managed with low molecular weight heparin, in the opinion of the Investigator, may 
be enrolled in the study provided they are switched to low molecular weight heparin at least 7 
days prior to receiving study treatment. 
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 
symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable 
angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring oxygen, known 
bleeding disorders, or any concomitant illness or social situation that would limit compliance with 
study requirements 
12. Known allergic reaction or intolerance to study medication components 
13. Known allergic reaction or intolerance to contrast media 
14. Subjects who, in the Investigator’s opinion, are not suitable for participation in this study 
Study Treatments 
Test drug:  Oraxol (oral HM30181AK-US + oral paclitaxel) 
• 
HM30181 methanesulfonate monohydrate – supplied as 15-mg HM30181AK-US tablets 
• 
Paclitaxel – supplied as 30-mg capsules 


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Treatment: 
• HM30181 15 mg tablet administered orally 1 hour before oral paclitaxel daily x 3 days weekly
x 16 weeks 
• Oral paclitaxel 205 mg/m2 daily x 3 days weekly x 16 weeks
• Subjects should fast for 6 hours before and 2 hours after Oraxol administration on all treatment
days
Management of Unacceptable Toxicity: 
Subjects experiencing unacceptable toxicity who have completed the first week of Oraxol treatment will 
have their Oraxol treatment delayed until the toxicity improves. 
Subjects whose unacceptable toxicity improves to CTCAE Grade 1 or baseline within 2 weeks of their 
last dose of Oraxol may continue treatment with dose reduction as described below: 
Dose Reduction after First Occurrence of Unacceptable Toxicity 
Treatment will resume at an oral paclitaxel dose of 165 mg/m2 per day for 3 consecutive days each 
week.  The HM30181 dose of 15 mg will be kept the same. 
Dose Reduction after Second Occurrence of Unacceptable Toxicity 
Treatment will resume at an oral paclitaxel dose of 130 mg/m2 per day for 3 consecutive days each 
week.  The HM30181 dose of 15 mg will be kept the same. 
Once the dose has been reduced, it cannot be increased at a later date.  
Discontinuation due to Unacceptability Toxicity: 
Oraxol treatment will be permanently discontinued for subjects who are unable to complete the first week 
of dosing due to unacceptable toxicity. 
After 2 dose reductions, subjects whose unacceptable toxicity does not improve to Grade 1 or baseline 
within 2 weeks of their last dose of Oraxol will have their Oraxol treatment permanently discontinued. 
Subjects who continue to experience unacceptable toxicity after 2 dose reductions will be discontinued 
from the study. 
Assessments 
Pharmacokinetic: 
PK sampling times for measurement of plasma concentrations of study drug are 
shown below. 
Treatment 
PK Sampling Timepointsa 
Oraxol 
(HM30181AK-US tablet + 
paclitaxel capsule) 
Week 1 (Days 1,2,3): Predose, and at 1,2, 3, and 4 hours 
postdose (all 24 subjects) 
Week 4 (Days 1,2,3): Predose, and at 1, 2, 3, and 4 hours 
postdose (all 24 subjects) 
a:  For purposes of PK sampling, study weeks will be counted consecutively from Week 1.  Week 4 PK 
sampling may be delayed at the discretion of the Investigator, eg, to allow the subject to recover from 
unacceptable toxicity.  In the event of a treatment delay, Week 4 PK samples should be obtained as soon as 
possible once the subject resumes treatment. 


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Safety: Safety will be assessed by evaluating the following parameters: 
• 
determining and recording all AEs including Common Terminology Criteria for Adverse Events 
(CTCAE) grades (for both increasing and decreasing severity) and SAEs 
• 
laboratory evaluation of hematology, blood chemistry, and urinalyses 
• 
vital sign measurements, physical examinations, and ECGs 
Activity:  Tumor assessment and response will be evaluated using RECIST v1.1 criteria both by 
investigator and by independent central radiology review committee.; PFS and OS 
Bioanalytical Methods 
Plasma concentrations of study drug will be measured using a validated liquid chromatography-tandem 
mass spectrometry (LC-MS/MS) assay. 
Statistical Methods 
A total of 24 evaluable subjects receiving Oraxol will be analyzed.  Subjects who do not have Week 4 
PK assessments for any reason will be replaced. 
Statistical analyses will be reported using summary tables, graphs, and data listings. Continuous 
variables will be summarized using the mean, standard deviation, median, minimum, and maximum.  
Categorical variables will be summarized by counts and by percentage of subjects in corresponding 
categories.  All raw data obtained from the eCRF as well as any derived data will be included in data 
listings. 
Analysis Sets 
Safety/Full Analysis Set:  The Safety population / Full Analysis Set will include all subjects who receive 
at least 1 dose of study treatment. 
Evaluable Set: The Evaluable population will include all protocol-eligible subjects who receive at least 
1 dose of study treatment and have at least 1 post-treatment PK evaluation. 
Pharmacokinetic Analyses 
Plasma concentrations for paclitaxel only will be analyzed to determine the following PK parameters:  
Cmax, Cmin, Cavg, AUC0-t, and AUCτ. 
Pharmacokinetic parameters will be summarized using the mean, standard deviation, median, minimum, 
and maximum.  Summaries of PK parameters will also include the geometric mean and the coefficient 
of variation. 
Summary PK and individual timepoints will be tabulated and displayed graphically and listed for all 
subjects. 
Safety Analyses 
For AEs, verbatim terms on the eCRF will be mapped to preferred terms (PTs) and system organ classes 
(SOCs) using the Medical Dictionary for Regulatory Activities (MedDRA; version 16.0 or higher).  The 
CTCAE criteria v4.03 will be used to grade severity of the AEs.  Subject incidence of AEs will be displayed 
by SOC.  The incidence of AEs will be summarized.  Adverse events will also be summarized by severity 
and relationship to study drug.  Subject incidence of SAEs will be displayed. 
Activity Analyses 
Tumor response rate and its 95% confidence interval (CI) will be evaluated based on the number of 
subjects with any postbaseline CR or PR per RECIST criteria both as evaluated by investigator and by 


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central radiology review committee. In addition, the incidence of tumor response at each clinical visit 
will be summarized.  Progression-free survival and overall survival will be estimated. 
Version and date 
v7.0_14 Aug 2018 
 
Schematic of Study Design: 
An overview of the study design is presented in Figure 1. 
 
 
Figure 1 
Schematic of Study Design for KX-ORAX-007 


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KEY ROLES 
PRINCIPAL INVESTIGATOR 
 
Name:  
Tsu-Yi Chao MD, DMS, PhD 
 
Address: 
Taipei Medical University Shuang Ho Hospital 
No.291, Zhongzheng Road 
Zhonghe District  
New Taipei City, 23561, Taiwan 
 
Telephone Number: 
+886227361661 ext 3229  
 
 
INVESTIGATORS 
 
This study will be conducted by qualified Investigators under the sponsorship of Kinex 
Pharmaceuticals, Inc. and PharmaEssentia (Taiwan) (the Sponsors) at approximately 6 sites in 
Taiwan. 
 


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BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
 
Background Information 
The name of the investigational product (IP) is Oraxol, an oral dosage form of the 
chemotherapeutic agent paclitaxel administered with a novel P-glycoprotein (P-gp) inhibitor, 
HM30181 methanesulfonate monohydrate (referred to in this document as HM30181).  
Experience to date indicates that co-administration of HM30181 allows for clinically relevant blood 
levels of paclitaxel to be achieved following oral dosing.  Oraxol is intended to allow for oral 
treatment of cancers that would otherwise be treated with intravenous (IV) paclitaxel.  
Intravenous paclitaxel is an approved treatment for breast cancer.  Paclitaxel 80 mg/m2 weekly is 
the most commonly used regimen for treatment of breast cancer patients.  Effective blood 
concentrations of paclitaxel and duration (AUC) can predict clinical outcomes. 
Oraxol is an oral dosage form of the chemotherapeutic agent paclitaxel administered with a novel 
P-glycoprotein (P-gp) inhibitor, HM30181, to enhance the oral absorption of paclitaxel in cancer 
patients. 
Phase1 and 2 clinical studies with HM30181A and oral paclitaxel (Oraxol) in 111 oncology 
patients showed that Oraxol was well tolerated.  The MTD was not reached, and no anaphylactic 
reactions were observed.  Premedication was not required for Oraxol treatment.  The overall 
safety profile of oral paclitaxel may be better than IV paclitaxel.  A Phase 2 clinical trial showed 
encouraging survival efficacy data in the treatment of gastric cancer.  
A clinical pharmacokinetic (PK) study showed that HM30181 15 mg plus oral paclitaxel 
205 mg/m2 administered for 3 consecutive days per week can produce a paclitaxel exposure 
(AUC) similar to that of 80 mg/m2 IV paclitaxel per week in cancer patients. 
Summary of Nonclinical Studies  
Results of primary and secondary pharmacodynamic studies confirm that HM30181A is effective 
in inhibiting P-gp, and when administered with paclitaxel as Oraxol, allows the systemic 
absorption of paclitaxel to therapeutically effective levels. 
In a battery of central nervous system (CNS), respiratory and cardiovascular safety pharmacology 
studies, HM30181A caused no adverse effects.  Oraxol caused minor reductions in body 
temperature in a CNS safety pharmacology study in rats, and reductions in PR and QRS intervals 
in cardiovascular safety pharmacology in dogs.  No effect doses were achieved for these effects.  
The effects caused by Oraxol are interpreted as being caused by the paclitaxel component of 
Oraxol, because of their absence in studies of HM30181A alone. 


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Pharmacokinetic and metabolism studies showed that HM30181A is poorly absorbed after oral 
administration, and absorption is less than dose proportional.  Absorbed HM30181A is widely 
distributed in tissues, but is present in low or non-detectable concentrations in the eye and 
nervous tissue.  HM30181A is not an inhibitor of major cytochrome P450 (CYP) enzymes.  Protein 
binding is high.  The PK of HM30181A is not affected by co-administration with paclitaxel. 
Paclitaxel is readily absorbed in therapeutically relevant concentrations when administered orally 
in combination with HM30181A.  Paclitaxel is widely distributed into tissues after oral 
administration, in a pattern similar to that seen after IV administration as Taxol.  HM30181A may 
modestly increase the tissue concentrations of paclitaxel after oral administration of both agents 
in combination. 
In oral toxicity studies of HM30181, no toxicity was observed after a single dose of 2000 mg/kg in 
rats.  Administration of HM30181A to rats was characterized by the occurrence of small increases 
in leucocyte counts and small decreases in lymphocyte counts; these changes were recoverable.  
Mesenteric lymph nodes were enlarged at doses ≥ 50 mg/kg, and histiocytosis in these lymph 
nodes was observed at doses ≥ 10 mg/kg (4-week study) or ≥ 50 mg/kg (13-week study).  In dogs, 
increases in total leucocyte and eosinophil counts occurred at doses of ≥50 mg/kg.  Enlargement 
of mesenteric lymph nodes associated with microscopically observed histiocytosis was also 
observed at these doses.  The HM30181A-related effects in dogs were reversible.  No other toxic 
effects of HM30181A occurred in oral toxicity studies of up to 13 weeks duration in rats and dogs.  
HM30181A is not genotoxic and caused no reproductive or fetal toxicity.  
Single and repeat dose administration of Oraxol caused toxicities characteristic of paclitaxel.  
These included leucopenia related to decreases in circulating neutrophils, lymphocytes and other 
leucocyte types; anemia associated with bone marrow suppression; hypocellularity/atrophy of 
lymphoid organs including the thymus; villous stunting and epithelial hyperplasia in the intestinal 
mucosa in dogs; and hepatic necrosis in dogs.  These changes were partially or fully reversible.  
All of the toxic effects seen in toxicity studies of Oraxol in rats and dogs are typical of the effects 
of paclitaxel.  None of the toxicity of Oraxol appears to be caused by the HM30181A component 
of the Oraxol.  Oraxol was not tested in genotoxicity or reproductive toxicity studies because its 
effects in such studies can be presumed to be the same as those caused by paclitaxel. 
Comprehensive data on the preclinical, toxicology, and clinical experience to date can be found 
in the Investigator’s Brochure. 
Summary of Clinical Data  
Previous human experience with HM30181 methanesulfonate monohydrate comes from 3 PK 
studies in healthy male subjects.  In these studies, a total of 81 individuals received single oral 
doses of HM30181 ranging from 1 to 900 mg and 24 individuals received multiple doses ranging 
from 60 to 360 mg per day for 5 days.  In addition to evaluating single- and multiple-dose safety 
and PK, 2 of these studies evaluated the effect of HM30181 methanesulfonate monohydrate on 


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the PK of loperamide, a P-gp substrate, and 1 study also compared the effects of HM30181 
methanesulfonate monohydrate to quinidine, a known P-gp inhibitor.  These data indicate that 
exposure to HM30181 methanesulfonate monohydrate increases with dose, but not in a dose-
proportional manner, and that the effect of HM30181 methanesulfonate monohydrate on P-gp 
may last for up to 15 days following a single dose of 10 mg or higher but is not as pronounced as 
that of 600 mg of quinidine. 
The HM-OXL-101 study attempted to define the maximum tolerated dose (MTD) for Oraxol in 
24 subjects with advanced solid cancer.  This was a “3+3” design in which cycles were 28 days 
and dosing with HM30181A tablets and an oral liquid formulation of paclitaxel was given on Days 
1, 8, and 15 of each cycle.  Paclitaxel doses evaluated ranged from 60 to 420 mg/m2.  HM30181A 
doses were half of paclitaxel doses (30 to 210 mg/m2).  The MTD was not reached in this study 
and dose escalation was stopped because of PK nonlinearity at paclitaxel doses above 
300 mg/m2.  The most common nonserious adverse events (AEs) were gastrointestinal (GI), 
hematologic, and alopecia.  Neutropenia was the event that led to either temporary (4 cases) or 
permanent (1 case) discontinuation of Oraxol.  The only serious adverse event (SAE) occurred at 
the paclitaxel dose of 420 mg/m2.  This subject was hospitalized with cholangio-hepatitis and 
recovered after treatment with endoscopic retrograde biliary drainage.  The event was considered 
unrelated to the study medication. 
HM-OXL-201 is a 2-part study including an initial MTD assessment of Oraxol doses 90, 120, or 
150 mg/m2 paclitaxel per day for 2 days (as liquid-filled capsules), with paclitaxel given 
concomitantly with a 15-mg HM30181AK tablet on Day 1 in patients with advanced malignant 
tumors, including advanced gastric cancer.  In the second part of this study, the selected dose of 
Oraxol, 150 mg/m2 per day, was given for 2 days per week, every 3 weeks out of a 4-week cycle.  
The Investigators were also given the flexibility of giving an additional 15-mg tablet of HM30181AK 
on Day 2 of each dosing week.  A total of 56 subjects enrolled in this study, 10 subjects with 
advanced malignant tumors in Part 1 and 46 subjects with advanced gastric cancer in Part 2.  The 
most common AEs were neutropenia, anorexia, diarrhea, nausea, and abdominal pain.  In the 
first part of this study, 1 subject had SAEs of pyrexia and bacteremia (probably not related to 
study treatment).  In the second part of the study, 26 SAEs occurred in 15 subjects.  Of these, 
3 subjects experienced at least 1 SAE considered at least possibly related to study treatment.  
These included 1 subject with diarrhea and neutropenia, 1 subject with fatigue, and 1 subject with 
nausea and vomiting.  Among 43 patients with advanced gastric cancer in the Intent-to-Treat (ITT) 
Population in Part 2 of this study, 4 patients (9.3%) had a partial response by Response 
Evaluation Criteria in Solid Tumors (RECIST) criteria.  The median overall survival was 10.7 
months (95% confidence interval [CI], 7.2-14.2). 
Pharmacokinetic results from these 2 studies showed that the paclitaxel maximum concentration 
(Cmax) and area under the curve extrapolated to infinity (AUC0-∞) increased with dose up to 
300 mg/m2 following administration of Oraxol.  At doses above 300 mg/m2, both Cmax and AUC0-∞ 
plateaued.  Half-life (t1/2) ranged from 19.9 to 32.1 hours, consistent with published values for 


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paclitaxel.  Metabolic ratios of p-3-hydroxy paclitaxel and 6α-hydroxy paclitaxel metabolites were 
0.1 ~ 0.25 and 0.04 ~ 0.13, respectively.  Following 2 consecutive daily doses of Oraxol at doses 
of 60, 90, or 150 mg/m2, minimal to no accumulation occurred in paclitaxel Cmax and AUC.  The 
Cmax and AUC0-24 ranged from 202 to 280 (Day 1) and 159 to 315 ng/mL (Day 2), and 611 to 894 
(Day 1) and 735 to 1081 ng·h/mL (Day 2), respectively, with minimal increase in Cmax across the 
dose levels.  Overall exposure on Day 2 was about 20% to 30% higher.  These data indicate that 
Oraxol may represent a clinically useful alternative to IV paclitaxel. 
Study ORAX-01-13-US is an ongoing “3+3” MTD study of Oraxol at a fixed dose of 270 mg 
(approximately 150 mg/m2 per day for a person with a body surface area [BSA]) of 1.8 m2) orally 
given 2 to 5 consecutive days per week for 3 out of 4 weeks.  Preliminary data indicate that the 
most common AEs are gastrointestinal.  Ten SAEs have been reported in 7 subjects; 1 case each 
of neoplasm posterior fossa mass, syncope, right upper quadrant pain, urosepsis, liver 
dysfunction, nausea, vomiting, abdominal pain, febrile neutropenia, and pain (not otherwise 
specified [NOS]).  Of these, febrile neutropenia, occurring in the 5-day cohort in Cycle 1 is the 
only SAE considered related to study treatment and is the only dose-limiting toxicity reported to 
date. 
A Phase 1 crossover study (Study ORAX-01-14-NZ) to determine the absolute bioavailability of 
Oraxol was conducted in New Zealand and is clinically complete.  Oraxol doses were 270 mg 
(approximately 150 mg/m2) (n=6), 274 mg/m2 (n=2) and 313 mg/m2 administered per day for 
2 consecutive days (n=2).  The reference treatment was paclitaxel 80 mg/m2 IV, administered 
over 1 hour as a one-time infusion.  Results show that the absolute bioavailability of paclitaxel in 
Oraxol is approximately 14% but the total drug exposure (AUC) of oral paclitaxel plateaus at a 
dose of approximately 300 mg/m2.  Therefore, an oral paclitaxel dose of approximately 205 mg/m2 
administered daily for 3 consecutive days per week (ie, a total weekly dose of 615 mg/m2) is likely 
to produce a paclitaxel exposure similar to that of 80 mg/m2 IV paclitaxel per week.  The only SAE 
reported in this study was urosepsis which occurred prior to receiving study treatment. 
 
Rationale 
Intravenous paclitaxel is an approved treatment for breast cancer.  Paclitaxel 80 mg/m2 weekly is 
the most commonly used regimen for treatment of breast cancer patients.  Effective blood 
concentrations of paclitaxel and duration (AUC) can predict clinical outcomes.  Data from Study 
ORAX-01-14-NZ (described above) showed that the dose used in this current study (KX-ORAX-
007) (Oraxol 205 mg/m2 administered for 3 consecutive days per week) is likely to produce a 
paclitaxel exposure (AUC) similar to that of 80 mg/m2 IV paclitaxel per week. 


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Potential Risks and Benefits 
 Potential Risks 
The toxicity caused by Oraxol appears to be caused by the paclitaxel component of the Oraxol, 
and those effects are predictable from the known toxicity profile of paclitaxel administered by the 
IV route.  It is therefore predicted from nonclinical and clinical studies that the human safety risks 
from Oraxol will be similar to those known to occur with paclitaxel, and precautions similar to those 
required when administering paclitaxel should be exercised when administering Oraxol. 
Serious AEs commonly occur in patients with cancer even in the absence of study drug exposure.  
Manifestations typically reflect progression of disease, with the clinical presentation varying 
depending on the affected organ system. 
 Known Potential Benefits 
Oraxol treatment resulted in encouraging survival results in the Phase 1/2 Study HM-OXL-201, 
with a median overall survival of 10.7 months (95% CI, 7.2-14.2), in patients with advanced gastric 
cancer who failed first-line chemotherapy.  Oraxol was given at a dose of 150 mg/m2 per day, 
taken 2 days per week for 3 weeks out of a 4-week cycle and was well tolerated. 
 


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OBJECTIVES 
 
Primary Study Objective 
The primary objective of the study is to investigate the PK (AUC) of orally administered paclitaxel 
(as Oraxol) in breast cancer patients. 
 
Secondary Study Objectives 
The secondary study objectives are to determine the safety and activity (response rate, 
progression-free survival [PFS], overall survival [OS]) of Oraxol in breast cancer patients. 
 
Study Outcome Measures 
 Primary Outcome Measures 
Primary Endpoint 
• 
Evaluation of PK parameters for oral paclitaxel 
 Secondary Outcome Measures 
Secondary Endpoints 
• 
Safety 
- Incidence of all AEs, including SAEs 
- Laboratory values 
- Other safety assessments including vital signs, physical exams, electrocardiograms 
(ECGs) 
• 
Activity 
- Tumor response rate, which is defined as the number of subjects with complete response 
(CR) or partial response (PR) at any post-baseline assessments expressed as the 
proportion of the total number of subjects in the Full Analysis Set  
- PFS and OS 


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STUDY DESIGN 
This is a multicenter, open-label, single-arm PK study in approximately 24 breast cancer patients 
for whom paclitaxel treatment is indicated.  Subjects will receive Oraxol 205 mg/m2 daily x 3 days 
weekly for up to 16 weeks.  Subjects must have measurable disease as per RECIST v1.1 criteria 1. 
The study will be conducted at approximately 6 sites in Taiwan.  The study period will be 
approximately 8 months (first person first visit to last person last visit [FPFV-LPLV]).  The duration 
of the study for each subject is approximately 21 weeks (up to 4 weeks for Screening/Baseline, 
16 weeks for treatment, and 1 week for follow-up). 
The study contains 3 periods:  the Screening / Baseline Period, the 16-week Treatment Period, 
and the 1-week Follow-up Period (Section 7).  A Final Visit will occur within 7 days of the last dose 
of study treatment.  After completion of Final Visit assessments, subjects will be contacted 
every 2 months to follow progression-free survival and overall survival.  New anti-cancer 
therapy will be collected. 
Subjects may be treated until disease progression, or unacceptable toxicity requiring more than 
2 dose reductions, or a maximum of 16 weeks.  If subjects achieve stable disease (SD), CR, or 
PR at Week 16, they may continue Oraxol treatment in a separate extension study. 
Pharmacokinetic parameters will be analyzed and various safety assessments (eg, AEs, 
laboratory tests) will be conducted throughout the study (Table 6), as well as imaging and tumor 
assessments which will be performed to evaluate tumor response. 
For purposes of PK sampling, study weeks will be counted consecutively from Week 1.  Week 4 
PK sampling may be delayed at the discretion of the Investigator, eg, to allow the subject to 
recover from unacceptable toxicity.  In the event of a treatment delay, Week 4 PK samples should 
be obtained as soon as possible once the subject resumes treatment. 
An overview of the study design is presented in Figure 1. 


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STUDY ENROLLMENT AND WITHDRAWAL 
In this study, the PK, safety, and activity of Oraxol (oral paclitaxel dose 205 mg/m2 daily x 3 days 
weekly) will be evaluated in adult females with breast cancer patients for whom paclitaxel 
treatment is indicated.  Subjects must have measurable disease as per RECIST v1.1 criteria.  
Approximately 24 subjects will be treated at approximately 6 sites in Taiwan.  
Subjects who do not meet all of the inclusion criteria or who meet any of the exclusion criteria will 
not be eligible to receive study treatment.  
 
Subject Inclusion Criteria 
Subjects must meet all of the following criteria to be included in this study: 
1. Signed written informed consent 
2. Women ≥18 years of age on day of consent 
3. Breast cancer in patients for whom treatment with IV paclitaxel at 80 mg/m2 as monotherapy 
has been recommended by their oncologist  
4. Measurable disease as per RECIST v1.1 criteria 
5. Adequate hematological status as demonstrated by not requiring transfusion support or 
granulocyte-colony stimulating factor (G-CSF) to maintain: 
• 
Absolute neutrophil count (ANC) ≥1.5 x 109/L 
• 
Platelet count ≥100 x 109/L 
• 
Hemoglobin (Hgb) ≥9 g/dL 
6. Adequate liver function as demonstrated by: 
• 
Total bilirubin of ≤1.5 mg/dL 
• 
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper 
limit of normal (ULN) or ≤5 x ULN if liver metastasis is present 
• 
Alkaline phosphatase (ALP) ≤3 x ULN or ≤5 x ULN if bone metastasis is present 
• 
Gamma glutamyl transferase (GGT) <10 x ULN 
7. Adequate renal function as demonstrated by serum creatinine ≤1.5 x ULN 
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
9. Life expectancy of at least 3 months 
10. Willing to fast for 6 hours before and 2 hours after Oraxol administration on all treatment 
days 
11. Willing to abstain from alcohol consumption for 3 days before the first dose of study drug 
through the completion of the second inpatient PK sampling period 


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12. Willing to refrain from caffeine consumption for 12 hours before each inpatient dosing period 
(Weeks 1 and 4) through the completion of protocol-specified PK sampling for that week 
13. Subjects must be postmenopausal (>12 months without menses) or surgically sterile (ie, by 
hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie, 
oral contraceptives, intrauterine device, double barrier method of condom and spermicide) 
and agree to continue use of contraception for 30 days after their last dose of assigned 
study treatment. 
14. Subjects who are of childbearing potential must have a negative serum pregnancy test at 
Screening and within 96 hours before Week 1 dosing. 
 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from this study: 
1. Have not recovered to ≤ Grade 1 toxicity from previous anticancer treatments or previous 
IPs 
2. If previously treated with a taxane (paclitaxel or docetaxel) as part of anthracycline-based 
adjuvant chemotherapy or for metastatic disease, the subject relapsed less than 1 year 
following treatment 
3. Subjects unable to swallow study medication in its intact form or have clinically significant 
malabsorption syndrome 
4. Only site of metastatic disease is unmeasurable according to RECIST v1.1 criteria 
5. Known CNS metastasis, including leptomeningeal involvement 
6. Received IPs within 14 days or 5 half-lives of the first study dosing day, whichever is longer 
7. Are currently receiving other medications intended for the treatment of their malignancy 
8. Women who are pregnant or breastfeeding 
9. Taking any of the following prohibited medications: 
• 
Strong inhibitors (eg, ketoconazole) or inducers (eg, rifampin or St. John's Wort) of 
CYP3A4 (within 2 weeks prior to the start of dosing in the study) 
• 
Strong inhibitors (eg, gemfibrozil) or inducers (eg, rifampin) of CYP2C8 (within 
2 weeks prior to the start of dosing in the study) 
• 
Strong P-gp inhibitors or inducers.  Subjects who are taking such medications but who 
are otherwise eligible may be enrolled if they discontinue the medication ≥1 week 
before dosing and remain off that medication through the end of study treatment. 
• 
An oral medication with a narrow therapeutic index known to be a P-gp substrate (eg, 
digoxin, dabigatran) within 24 hours prior to start of dosing in the study 
10. Use of warfarin.  Subjects receiving warfarin who are otherwise eligible and who may be 
appropriately managed with low molecular weight heparin, in the opinion of the 


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Investigator, may be enrolled in the study provided they are switched to low molecular 
weight heparin at least 7 days prior to receiving study treatment. 
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 
symptomatic congestive heart failure, myocardial infarction within the last 6 months, 
unstable angina pectoris, cardiac arrhythmia, chronic pulmonary disease requiring 
oxygen, known bleeding disorders, or any concomitant illness or social situation that would 
limit compliance with study requirements 
12. Known allergic reaction or intolerance to study medication components 
13. Known allergic reaction or intolerance to contrast media 
14. Subjects who, in the Investigator’s opinion, are not suitable for participation in this study 
 
Treatment Assignment Procedures 
 Randomization Procedures 
Not applicable; this is a nonrandomized, open-label study. 
 Masking Procedures 
Not applicable; this is a nonrandomized, open-label study. 
 Reasons for Withdrawal 
A subject may elect to discontinue from the study at any time for any reason. 
The Investigator may discontinue treating a subject with study treatment or withdraw the subject 
from the study at any time for safety or administrative reasons. 
Subjects may continue the study treatment until any of the following primary reasons for 
discontinuation occurs:  
• 
Death 
• 
Progression of disease 
○ computed tomography (CT) or magnetic resonance imaging (MRI) confirmed by 
RECIST v1.1 criteria and 
 
 
−  Progression of disease not associated with AE(s) or 
 
 
−  Progression of disease associated with AE(s) 
○ other clinical findings indicating disease progression, eg, pain with bone 
metastases or seizure with brain metastases 
• 
Unacceptable toxicity  
• 
AEs not associated with progression of disease 


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• 
Noncompliance (Investigator needs to describe) 
• 
Withdrawal of consent (subject asked but not required to give a reason) 
- Withdrawal of consent must be qualified as with or without permission to obtain 
additional assessments after the time of withdrawal 
• 
Termination of the study by the Sponsor 
• 
Other (Investigator must describe) 
In addition to the primary reason, the subject may have indicated one or more of the above as 
secondary reasons for discontinuation.  Investigators must document the actual reason(s) why 
they decided to discontinue subjects or why subjects withdrew consent, as applicable. 
Study disposition information will be collected and documented on the electronic case report form 
(eCRF). 
 Handling of Withdrawals 
If a subject discontinues study treatment, the subject will complete the protocol-specified 
procedures and assessments for the Final Visit unless the subject withdraws consent.  The 
Investigator should confirm whether a subject will withdraw from study treatment but agree to 
continue 
protocol-specified, 
off-treatment 
procedures 
and 
long-term 
follow-up 
for 
progression-free survival, overall survival, and new anti-cancer therapy at the Final Visit (as 
indicated in Table 6) or whether the subject will withdraw consent.  If a subject withdraws consent, 
the date will be documented in the source documents.  The Discontinuation from Treatment eCRF 
page will be completed indicating the primary reason for discontinuation and all other reason(s) 
contributing to the subject’s discontinuation from treatment.  In addition, the date of last dose of 
study drug(s) will be recorded on the Study Drug Dosing eCRF page. 
A subject who has ceased to return for visits will be followed up by mail, phone, or other means 
to gather information such as the reason for failure to return, the status of treatment compliance, 
the presence or absence of AEs, and clinical courses of signs and symptoms.  This information 
will be recorded on the eCRF. 
Subjects who do not have Week 4 PK assessments for any reason will be replaced. 
Subjects who have their Week 4 PK assessments and subsequently discontinue will not be 
replaced. 
 Termination of Study  
The Sponsor reserves the right to discontinue the study for medical reasons or any other reason 
at any time.  If a study is prematurely terminated or suspended, the Sponsor will promptly inform 
the Investigators/institutions and regulatory authorities of the termination or suspension and the 
reason(s) for the termination or suspension.  The Institutional Review Board (IRB)/Independent 


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Ethics Committee (IEC) will also be informed promptly and provided the reason(s) for the 
termination or suspension by the Sponsor or by the Investigator/institution, as specified by the 
applicable regulatory requirement(s). 
The Investigator reserves the right to discontinue the study should his/her judgment so dictate.  If 
the Investigator terminates or suspends a study without prior agreement of the Sponsor, the 
Investigator should inform the institution where applicable, and the Investigator/institution should 
promptly inform the Sponsor and the IRB/IEC and provide the Sponsor and the IRB/IEC with a 
detailed written explanation of the termination or suspension.  Study records must be retained as 
noted above. 


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STUDY INTERVENTION/INVESTIGATIONAL PRODUCT 
 
Study Product Description 
 Formulation, Packaging, and Labeling 
 
Formulations 
Oral paclitaxel will be supplied as 30 mg capsules.  HM30181AK-US will be supplied as 15 mg 
tablets. 
 
Chemical Name, Structural Formula of Paclitaxel 
• 
Study drug code: 
Paclitaxel 
• 
Chemical name: 
5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 
4,10-diacetate 2-benzoate 13- ester with (2R,3S)-N-benzoyl-3-phenylisoserine 
• 
Molecular formula: C47H51NO14 
• Molecular weight: 
853.91 
• 
Structural formula:  
 


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Chemical Name, Structural Formula of HM30181 Methanesulfonate 
Monohydrate 
• 
Study drug code: 
 
HM30181AK-US 
• 
Chemical name: 
 
N-(2-(2-(4-(2-(6,7-Dimethoxy-3,4-
dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-2H-tetrazol-5-yl)-4,5-
dimethoxyphenyl)-4-oxo-4H-chromene-2-carboxamide Methanesulfonate 
monohydrate 
• 
Molecular formula: C38H36N6O7·CH3SO3H·H2O 
• 
Molecular weight: 
802.85 (methanesulfonate monohydrate salt) / 688.72 (free base) 
• Structural formula: 
NH
H3CO
H3CO
O
O
O
N
N
N
N
N
OCH3
OCH3
S
O
O
OH
H3C
H2O
 
 
Packaging and Labeling 
Investigational product will be packaged and labeled in a manner consistent with the study and 
will be designed by:  
Kinex Pharmaceuticals, Inc. 
1001 Main Street 
Suite 600 
Buffalo, NY 14203 
United States 
Lot information, including expiration dates, if necessary, will be recorded for Oraxol (HM3018AK-
US tablets and oral paclitaxel capsules). 
Labels will be nonremovable in nature.  Labels for the IP (Oraxol [oral paclitaxel and HM30181AK-
US]) will be in accordance with regional/local regulations and will include (but will not be limited 
to) the following information: 
• 
For clinical study use only 
• 
Name and address of the Sponsor 
• 
Chemical name/drug identifier 
• 
Lot number/batch number 
• 
Storage conditions, expiration date if necessary 


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 Product Storage and Stability 
Study drug will be stored in accordance with labelled storage conditions.  Temperature monitoring 
is required at the storage location to ensure that the study drug is maintained within an established 
temperature range.  The Investigator is responsible for ensuring that the temperature is monitored 
throughout the total duration of the trial and that records are maintained; the temperature should 
be monitored continuously by using either an in-house validated data acquisition system, a 
mechanical recording device, such as a calibrated chart recorder, or by manual means, such that 
minimum and maximum thermometric values over a specific time period can be recorded and 
retrieved as required. 
 
Dosage, Preparation and Administration of Study 
Intervention/Investigational Product 
The IP in the study is Oraxol.  Oraxol is an oral dosage form of the chemotherapeutic agent 
paclitaxel administered with a novel P-gp inhibitor, HM30181.  See sections below and Table 1 
for a description of treatments administered. 
 Description and Justification of Dosage Regimen 
Previous experience with HM30181 indicates clinically significant P-gp inhibition with an 
acceptable safety profile.  Systemic P-gp inhibition is not observed.  Currently, HM30181 is being 
given at a dose of 15 mg on each dosing day.  Absorption of orally administered paclitaxel appears 
to plateau at doses above 300 mg/m2 when given with HM30181.  The dose of HM30181A of 
15 mg daily is being used in current studies of Oraxol based on PK data from healthy volunteer 
studies that examined the inhibitory effect of HM30181A on gut P-gp (see the Investigator's 
Brochure). 
Intravenous paclitaxel is an approved treatment for breast cancer.  Paclitaxel 80 mg/m2 weekly is 
the most commonly used regimen for treatment of breast cancer patients.  Effective blood 
concentrations of paclitaxel and duration (AUC) can predict clinical outcomes.  As shown in Study 
ORAX-01-14-NZ (described above), the dose used in this study (Oraxol 205 mg/m2 administered 
for 3 consecutive days per week) is likely to produce a paclitaxel exposure (AUC) similar to that 
of 80 mg/m2 IV paclitaxel per week. 
 Treatments Administered 
Information regarding study treatment is provided in Table 1. 


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Table 1 
Treatments Administered in KX-ORAX-007 
 
Strength 
Dose Form / 
Route of 
Administration 
Number Dispensed and 
Frequency 
Study Days Administered 
Investigational Product 
HM30181AK-US 
15 mg 
Tablet taken 
orally 
1 × 15-mg tablet, on 
designated treatment 
mornings, 1 hour before 
oral paclitaxel 
Days 1-3, weekly for 16 weeks 
Paclitaxel 
30 mg 
Capsules taken 
orally 
Number dispensed based 
on calculated doses 
(205 mg/m2 once on 
designated treatment 
mornings) 
Days 1-3, weekly for 16 weeks 
 Dosing Administration of Study Drugs 
Information regarding dosing and dispensing will be included in a Pharmacy Manual provided to 
the sites. 
 
Fasting Requirements 
Subjects will be instructed to fast, having nothing to eat or drink (except water) for at least 6 hours 
before HM30181 dosing on each Oraxol dosing day and to continue to fast for 2 hours after oral 
paclitaxel dosing.  Subjects may take other medications as directed.  Subjects may have water 
1 hour after completion of Oraxol dosing and as needed with other prescribed medications. 
 
Premedication 
Anti-emetics should be given on each day of Oraxol administration, with the first dose of anti-
emetic given at the same time as HM30181.  5-HT3 or NK-1 antagonists should be used for 
prophylaxis or initial treatment of nausea or vomiting.  Steroids or H-1 receptor antagonists are 
not allowed as anti-emetics for subjects taking Oraxol. 
Steroids or H-1 receptor antagonists should be given only if hypersensitivity-type reactions occur 
(including dyspnea with or without bronchospasm, urticaria, flushing or rashes, blood pressure 
changes, or angioedema).  For subjects who may experience hypersensitivity type-reactions, 
premedication with steroids or H-1 antagonists may be given before subsequent doses, if clinically 
indicated. 
 
Oraxol Dosing 
The calculated oral paclitaxel dose (based on BSA) for each subject will be rounded up to the 
closest number of 30-mg paclitaxel capsules to administer Oraxol (oral paclitaxel dose 205 mg/m2 
QD) for 3 consecutive days weekly. 
 
 


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Oraxol will be administered as follows: 
•
HM30181AK-US tablet will be administered as a single oral dose of 15 mg on each dosing
day approximately 1 hour before paclitaxel capsules.
•
Paclitaxel capsules will be administered as a single oral dose with water each dosing day.
•
Both HM30181 and paclitaxel should be taken with approximately 120 to 240 mL of water.
The amount of water consumed with HM30181AK-US and oral paclitaxel dosing in the clinic must 
be documented. 
On PK sampling days, in the event vomiting occurs within 4 hours postdose of oral paclitaxel, the 
Investigator should contact Kinex Pharmaceuticals, Inc., Taiwan immediately. 
Modification of Study Intervention/Investigational Product for a 
Subject 
Unacceptable Toxicity, Dose Interruption, and Dose Reduction 
Unacceptable toxicity occurs when any of the following events, graded according to Common 
Terminology Criteria for Adverse Events (CTCAE) v4.03 2 (or later) criteria, are considered at 
least possibly related to Oraxol: 
•
ANC ≤0.8 x 109/L
•
Grade 3 or 4 ANC plus fever or Grade 3 or 4 ANC with bacteremia or sepsis
•
Grade 3 thrombocytopenia (<50 x 109/L platelets) for more than 7 days, or
accompanied by clinically significant bleeding
•
Grade 4 thrombocytopenia (<25 x 109/L platelets) regardless of duration or clinical
manifestations
•
Grade ≥3 nausea, vomiting, or diarrhea persisting for more than 48 hours despite
optimal medical management
•
Grade ≥3 nonhematologic abnormalities not listed above.  This does not include:
o
laboratory abnormalities not considered to be SAEs and which resolve back
to Grade 1 or baseline within 7 days
o
alopecia
o
anorexia or asthenia which resolves within 7 days
•
Nonhematologic toxicities and hematologic toxicities not mentioned above which cause
a dose delay of >7 days
Management of Unacceptability Toxicity: 


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Subjects experiencing unacceptable toxicity who have completed the first week of Oraxol 
treatment will have their Oraxol treatment delayed until the toxicity improves.   
Subjects whose unacceptable toxicity improves to CTCAE Grade 1 or baseline within 2 weeks of 
their last dose of Oraxol may continue treatment with dose reduction as described below: 
Dose Reduction after First Occurrence of Unacceptable Toxicity 
Treatment will resume at an oral paclitaxel dose of 165 mg/m2 per day for 3 consecutive days 
each week.  The HM30181 dose of 15 mg will be kept the same. 
Dose Reduction after Second Occurrence of Unacceptable Toxicity 
Treatment will resume at an oral paclitaxel dose of 130 mg/m2 per day for 3 consecutive days 
each week.  The HM30181 dose of 15 mg will be kept the same. 
Once the dose has been reduced, it cannot be increased at a later date. 
Discontinuation due to Unacceptability Toxicity: 
Oraxol treatment will be permanently discontinued for subjects who are unable to complete the 
first week of dosing due to unacceptable toxicity. 
After 2 dose reductions, subjects whose unacceptable toxicity does not improve to Grade 1 or 
baseline within 2 weeks of their last dose of Oraxol will have their Oraxol treatment permanently 
discontinued. 
Subjects who continue to experience unacceptable toxicity after 2 dose reductions will be 
discontinued from the study. 
Accountability Procedures for the Study Intervention / 
Investigational Products 
All study drugs will be supplied to the Principal Investigator (or a designated pharmacist) by the 
Sponsor.  Drug supplies must be kept in an appropriate secure area (eg, locked cabinet) and 
stored according to the conditions specified on the drug labels.  The Investigator (or a designated 
pharmacist) must maintain an accurate record of the shipment and dispensing of the study drug 
in a drug accountability ledger, a copy of which must be given to the Sponsor at the end of the 
study.  An accurate record of the date and amount of study drug dispensed to each subject must 
be available for inspection at any time.  Designated study personnel will visit the site and review 
these documents along with all other study conduct documents at appropriate intervals once study 
drug has been received by the site. 


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All drug supplies are to be used only for this study and not for any other purpose.  The Investigator 
(or site personnel) must not destroy any drug labels or any partly used or unused drug supply 
before approval to do so by the Sponsor.  At the conclusion of the study and as appropriate during 
the study, the Investigator (or a designated pharmacist) will return all used and unused drug 
containers, drug labels, and a copy of the completed drug disposition form to personnel 
designated by the Sponsor or, when approval is given by the Sponsor, will destroy supplies and 
containers at the site. 
The Investigator and the study staff (or if regionally required, the head of the medical institution 
or the designated pharmacist) will be responsible for the accountability of all study drugs 
(dispensing, inventory, and record keeping) following the Sponsor’s standard operating 
procedures (SOPs) and adherence to Good Clinical Practice (GCP) guidelines as well as local or 
regional requirements. 
Under no circumstances will the Investigator allow the study drugs to be used other than as 
directed by this protocol.  Study drugs will not be dispensed to any individual who is not enrolled 
in the study. 
The site must maintain an accurate and timely record of the following:  receipt of all study drugs, 
dispensing of study drugs to the subject, collection and reconciliation of unused study drugs that 
are either returned by the subjects or shipped to the site but not dispensed to subjects, and return 
of reconciled study drugs to the Sponsor or (where applicable) destruction of reconciled study 
drugs at the site.  This includes, but may not be limited to: (a) documentation of receipt of study 
drugs, (b) study drugs dispensing/return reconciliation log, (c) study drugs accountability log, (d) 
all shipping service receipts, (e) documentation of returns to the Sponsor, and (f) certificates of 
destruction for any destruction of study drugs that occurs at the site.  All forms will be provided by 
the Sponsor.  Any comparable forms that the site wishes to use must be approved by the Sponsor. 
The study drugs and inventory records must be made available, upon request, for inspection by 
a designated representative of the Sponsor or a representative of a health authority (eg, United 
States Food and Drug Administration [FDA]).  As applicable, all unused study drugs and empty 
and partially empty containers from used study drugs are to be returned to the Investigator (or if 
regionally required, the head of the medical institution or the designated pharmacist) by the 
subject and, together with unused study drugs that were shipped to the site but not dispensed to 
subjects, are to be returned to the Sponsor’s designated central or local depot(s) during the study 
or at the conclusion of the study, unless provision is made by the Sponsor for destruction of study 
drugs and containers at the site.  Destruction at the site will only occur under circumstances where 
regulation or supply type prohibits the return of study drugs to the central or local depot(s).  
Approval for destruction to occur at the site must be provided by the Sponsor in advance.  Upon 
completion of drug accountability and reconciliation procedures by the site’s personnel and 
documentation procedures by the Sponsor’s personnel, study drugs that are to be returned to the 
Sponsor’s designated central or local depot(s) must be boxed, sealed, and shipped back to the 


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central or local depot(s) following all local regulatory requirements.  In some regions, study drugs 
may be removed from the site and hand delivered to the central or local depot by Sponsor 
representatives.  Where study drugs are approved for destruction at the site, destruction will occur 
following the site’s standard procedures and certificates of destruction will be provided to the 
Sponsor. 
Drug accountability will be reviewed during site visits and at the completion of the study. 
 
Assessment of Subject Compliance with Study Intervention / 
Investigational Product  
Subjects will be assessed for adherence to dosing schedule.  At the scheduled clinic visits, 
subjects should bring all used and unused study drug to the clinical site.  These will be checked 
by site personnel and a capsule and tablet count will be performed before subjects are dispensed 
a new supply of study drugs.  
Study drug should be taken on consecutive days of the week at approximately the same time 
each morning.   
Subjects will be given information cards on which they will record their dosing information.  
Records of treatment compliance for each subject will be kept during the study.  Designated study 
personnel will review treatment compliance during site visits and at the completion of the study. 
 
Concomitant Medications/Treatments 
All medications (prescription and nonprescription), treatments, and therapies taken from 28 days 
before the initiation of the study through the final study visit, must be recorded on the eCRF.  A 
complete oncologic treatment history will be recorded on the Oncologic Treatment History eCRF. 
Any medication (including nonprescription remedies) or therapy administered to the subject during 
the course of the study (starting at the date of informed consent) will be recorded on the 
Concomitant Medication eCRF.  The Investigator will record any AE on the Adverse Events eCRF 
for which the concomitant medication/therapy was administered. 
Subjects are excluded from participation in this study are those who are currently taking: 
• 
strong inhibitors (eg, ketoconazole) or inducers (eg, rifampin or St. John's Wort) of 
cytochrome P450 (CYP) 3A4 (within 2 weeks prior to the start of dosing in the study) 
• 
strong inhibitors (eg, gemfibrozil) or inducers (eg, rifampin) of CYP2C8 (within 2 weeks 
prior to the start of dosing in the study) 
• 
strong P-glycoprotein (P-gp) inhibitors or inducers.  Subjects who are taking such 
medications but who are otherwise eligible may be enrolled if they discontinue the 


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medication ≥1 week before dosing and remain off that medication through the end of 
study treatment. 
• 
an oral medication with a narrow therapeutic index known to be a P-gp substrate (eg, 
digoxin, dabigatran) within 24 hours prior to start of dosing in the study 
A list of drugs prohibited due to potential drug-drug interactions will be provided to the sites as 
part of the Pharmacy Manual. 
Subjects should not start prohibited medications while enrolled in this protocol. 
Use of warfarin is not permitted (use of low molecular weight heparin is allowed). 
Anti-emetics should be given on each day of Oraxol administration, with the first dose of anti-
emetic given at the same time as HM30181.  5-HT3 or NK-1 antagonists should be used for 
prophylaxis or initial treatment of nausea or vomiting.  Steroids or H-1 receptor antagonists are 
not allowed as anti-emetics for subjects taking Oraxol. 
Steroids or H-1 receptor antagonists should be given only if hypersensitivity-type reactions occur 
(including dyspnea with or without bronchospasm, urticaria, flushing or rashes, blood pressure 
changes, or angioedema).  For subjects who may experience hypersensitivity type-reactions, 
premedication with steroids or H-1 antagonists may be given before subsequent doses, if clinically 
indicated. 
The decision to administer a prohibited medication/treatment is done with the safety of the study 
subject as the primary consideration. 


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STUDY SCHEDULE 
Screening/Baseline 
The Screening/Baseline Period will last no longer than 28 days.  Subjects will be screened within 
28 days of the first dose of study drug.  All screening assessments/evaluations, as detailed in 
Table 6, will be performed after the subject provides informed consent and eligibility criteria are 
met. 
 
Treatment 
The Treatment Period will begin on Day 1, Week 1.  The dose and timing of administration of 
study treatments are as follows: 
•
Oraxol – 15 mg oral HM30181 methanesulfonate monohydrate plus 205 mg/m2 oral
paclitaxel administered once daily for 3 consecutive days, weekly for 16 weeks (HM30181
will be administered 1 hour before oral paclitaxel on all dosing days.)
All subjects will be housed in the clinic from the night before dosing on Week 1, Day 1 through 
the end of PK sampling on Day 3. 
For Week 4 PK sampling, subjects will be housed in the clinic from the night before dosing on 
Week 4, Day 1 through the end of PK sampling on Day 3. 
During PK sampling days, Oraxol will be administered to the subject in the clinic on scheduled 
dosing days. 
Safety and activity assessments evaluations, as detailed in Table 6, will be performed during the 
Treatment Period. 
Follow-up 
Subjects will be requested to participate in long-term follow-up for progression-free survival and 
overall survival.  New anti-cancer therapy will be collected.  After completion of this study, subjects 
or designated family members or physicians may be contacted every 2 months to determine if the 
patient has had progressive disease or whether the subject remains alive, or if any new anti-
cancer therapy has been taken. 
If a subject completes the study or discontinues the study at any time, a Final Visit will occur within 
7 days after the last dose of study treatment.  Safety assessments, as detailed in Table 6, will be 
performed at the Final Visit.  If a subject discontinues the study due to progression of disease, 


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the Final Visit assessments can be performed at the last on-treatment visit.  If possible, this visit 
should be scheduled before the subject receives additional chemotherapy. 
 
Early Termination Visit 
Subjects may continue treatment until any of the discontinuation criteria occurs as described in 
Section 5.3.3.  If a subject discontinues the study at any time, a Final Visit will occur within 7 days 
after the last dose.  Safety assessments, as detailed in Table 6, will be performed at the Final 
Visit. 
 
Unscheduled Visit  
Unscheduled visits will occur only at the discretion of the Investigator.  Results of any 
assessments performed at unscheduled visits will be entered into the clinical database. 


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STUDY PROCEDURES/EVALUATIONS 
 
Clinical Evaluations 
All assessments should be performed on the specified weeks/day(s) designated on the Schedule 
of Procedures and Assessments (Table 6). 
 Screening/Baseline Assessments 
Subjects must be screened within 28 days prior to Week 1 Day 1 dosing. 
 
Demography 
Subject demographic information will be collected at the Screening/Baseline Visit.  Demographic 
information includes date of birth (or age), sex, race/ethnicity. 
 
Body Surface Area 
Height (recorded at Screening/Baseline) and weight (with indoor clothing) will be measured to 
calculate BSA.  Sites may use any of the established formula for BSA, but must use the same 
formula for all subjects at their site, and the method of BSA calculation must be recorded on the 
eCRF for each subject. 
 
Medical/Surgical/Oncology History 
Medical history will be obtained at Screening/Baseline and will include:  
• 
a complete medical and surgical history; childhood diseases are not required and common 
colds are not required unless it is ongoing at Screening/Baseline 
• 
a complete oncology history (including all malignancies, if known, and currently, 
regardless of diagnosis date or status, eg, skin cancer >5 years).  The Tumor, Node, 
Metastases (TNM) status at time of diagnosis and Screening/Baseline will be recorded.  
For the subject’s qualifying breast cancer diagnosis, estrogen receptor status, 
progesterone receptor status, and human epidermal growth factor receptor 2 status will 
be recorded (positive, negative, or unknown). 
• 
complete oncology treatment history including all commercial and IPs, radiation and other 
prescribed and nonprescription therapies dating back to the initial diagnosis  
All medical and surgical history must be noted on the eCRF.  A complete oncology history and a 
complete oncology treatment history will also be recorded on the Oncology History and Oncology 
Treatment History eCRF. 


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Eastern Cooperative Oncology Group Performance Status 
The subject’s performance status should be assessed according to ECOG criteria 3 (Appendix B).  
ECOG will be assessed at Screening/Baseline.  Subjects with an ECOG >1 at Screening/Baseline 
must be excluded from the study. 
Prior Medications 
Prior non-oncologic medications taken within 28 days before Day 1, including nonprescription 
remedies, vitamins, etc, will be recorded at Screening/Baseline. 
Assessment of Activity 
Computed Tomography/Magnetic Resonance Imaging 
To assess tumors, CT and/or MRI scans will be conducted as designated on the Schedule of 
Procedures and Assessments (Table 6) as follows.  During the Screening/Baseline Period, a 
baseline scan will be conducted before the first dose on Week 1, Day 1 of Oraxol treatment, as 
close to Day 1 as possible.  Subsequent scans will be conducted every 8 weeks (at Weeks 8 and 
16) until documented progression.  Unscheduled scans should be conducted, if clinically
indicated, per the discretion of the Investigator.  Results of these unscheduled scans will be 
entered into the clinical database. 
Computed tomography and/or MRI scans of the chest, abdomen, and pelvis will be conducted at 
Baseline and repeated at all assessment times to determine the possible change in tumor size at 
the respective sites.  
RECIST Tumor Assessment 
Tumor status will be evaluated using RECIST v1.1 criteria (Appendix C) by the Investigator at 
each tumor assessment timepoint as discussed above in Section 8.1.2.1. 
All radiologic imaging should be sent to the independent central radiology review committee for 
evaluation when the patients completed Final Visit. Detailed information please refer to the charter 
for Central Radiology Review Committee. 
In addition to using the RECIST criteria, the Investigator must consider all other clinical 
information as part of tumor status evaluation.  The Investigator must record his/her tumor 
assessment based on each of these factors, including descriptions of nonmeasurable disease 
and other clinical information.  Results and interpretations of all scans or x-rays performed will be 
recorded on the eCRF. 
Long-term follow up for progression-free survival and overall survival: 
Subjects will be requested to participate in long-term follow-up for progression-free survival and 
overall survival.  Subjects or designated family members or physicians may be contacted every 


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2 months to determine if the patient has had progressive disease or whether the subject remains 
alive or is taking any new anti-cancer therapy. 
 
 
Pharmacokinetics 
For purposes of PK sampling, study weeks will be counted consecutively from Week 1.  Week 4 
PK sampling may be delayed at the discretion of the Investigator, eg, to allow the subject to 
recover from unacceptable toxicity.  In the event of a treatment delay, Week 4 PK samples should 
be obtained as soon as possible once the subject resumes treatment. 
All subjects will be housed in the clinic from the night before dosing on Week 1, Day 1 through 
the end of PK sampling on Day 3. 
For Week 4 PK sampling, subjects will be housed in the clinic from the night before dosing on 
Week 4, Day 1 through the end of PK sampling on Day 3. 
During PK sampling days, Oraxol will be administered to the subject in the clinic on scheduled 
dosing days. 
As designated on the Schedule of Procedures/Assessments (Table 6), blood samples 
(approximately 5 mL per testing timepoint) will be collected for analysis of plasma concentrations 
of oral paclitaxel starting at Week 1, Days 1-3, and again at Week 4, Days 1-3.  PK sampling 
times are presented in Table 3 (Week 1) and Table 4 (Week 4).  A ±10-minute window will be 
allowed for all PK sampling timepoints.  The actual times of PK sampling will be recorded.  
Reasons must be provided for all samples collected outside of the ±10-minute window.  All 
samples collected early, even within the 10-minute window, must also have reasons provided. 
Table 2 presents the amounts of blood (mL) that will be collected over the course of the study for 
PK analysis. 


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Table 2 
Blood Collection Volumes for Pharmacokinetic 
Analyses 
 
Oraxol 
(paclitaxel and HM30181) 
 
Week 1 
Week 4 
Volume per timepoint (mL) 
5 
5 
Number of timepoints 
15 
15 
Total (mL) 
75 
75 
Total (mL) 
150 
Samples will be analyzed for paclitaxel levels using validated liquid chromatography-tandem 
mass spectrometry (LC-MS/MS) assay. 
 
 


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Table 3 
Pharmacokinetic Sampling for Oral Paclitaxel - Week 1:  Days 1 to 3  
Week 1:  
Dosing Days 
Dosing Days 1a, 2b, and 3c 
Time after dosing on 
designated dosing days 
0 
(predose) 
1 h 
2 h 
3 h 
4 h 
PK Sample 
X 
X 
X 
X 
X 
h = hours; PK = pharmacokinetic. 
Note:  A ±10-minute window will be allowed for all PK sampling timepoints.  The actual times of PK sampling will be 
recorded.  Reasons must be provided for all samples collected outside of the ±10-minute window.  All samples 
collected early, even within the 10-minute window, must also have reasons provided. 
a:  Day 1 dosing:  predose, and at 1, 2, 3, and 4 h after the first dose (PK sampling times on Day 1). 
b:  Day 2 dosing:  predose, and at 1, 2, 3, and 4 h after the second dose (PK sampling times on Day 2). 
c:  Day 3 dosing:  predose, and at 1, 2, 3, and 4 h after the third dose (PK sampling times on Day 3). 
 
 
Table 4 
Pharmacokinetic Sampling for Oral Paclitaxel - Week 4:  Days 1 to 3  
Week 4:  
Dosing Days 
Dosing Days 1a, 2b, and 3c 
Time after dosing on 
designated dosing 
days 
0 
(predose) 
1 h 
2 h 
3 h 
4 h 
PK Sample 
X 
X 
X 
X 
X 
h = hours; PK = pharmacokinetic. 
Note:  A ±10-minute window will be allowed for all PK sampling timepoints.  The actual times of PK sampling will be 
recorded.  Reasons must be provided for all samples collected outside of the ±10-minute window.  All samples collected 
early, even within the 10-minute window, must also have reasons provided. 
a:  Day 1 dosing:  predose, and at 1, 2, 3, and 4 h after the first dose (PK sampling times on Day 1). 
b:  Day 2 dosing:  predose, and at 1, 2, 3, and 4 h after the second dose (PK sampling times on Day 2). 
c:  Day 3 dosing:  predose, and at 1, 2, 3, and 4 h after the third dose (PK sampling times on Day 3). 
 Specimen Preparation, Handling, and Shipping 
A description of collection, handling, and shipping procedures for PK samples will be provided to 
the sites in a laboratory manual. 


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ASSESSMENT OF SAFETY 
 
Specification of Safety Parameters 
Safety will be assessed by evaluating the following parameters: 
• 
determining and recording all AEs including CTCAE grades (for both increasing and 
decreasing severity) and SAEs 
• 
laboratory evaluation of hematology, blood chemistry, and urinalyses (Table 5) 
• 
vital sign measurements, physical examinations, and ECGs  
 
Methods and Timing for Assessing, Recording, and Analyzing 
Safety Parameters 
 Adverse Events 
Adverse events will be assessed and recorded at all clinic visits.  In between clinic visits, subjects 
will be instructed to call designated study personnel if they experience any adverse events. 
An AE is any untoward medical occurrence in a patient or clinical investigation subject, and 
includes events occurring from the time a subject signs the informed consent form (ICF) through 
the last subject contact.  An AE does not necessarily have a causal relationship with the medicinal 
product. 
Treatment-emergent adverse events (TEAEs) are those AEs which occur at any time from the 
initiation of dosing with the study medication up through the last subject contact.  Adverse events 
occurring at any time following the subject’s signing of the ICF up to the time immediately prior to 
dosing initiation with study medication are, unless associated with performance of a required 
study procedure, typically considered unrelated a priori to study medication, but are nonetheless 
reported.  
For this study, the study drug is Oraxol. 
The criteria for identifying AEs are: 
• 
any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of an IP, whether or not 
considered related to the IP 
• 
any new disease or exacerbation of an existing disease.  This includes any AEs 
associated with progression of disease.  Note, however that in this protocol, progression 
of disease is captured as a secondary endpoint under RECIST 1.1, and is not itself 


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considered an AE. 
• 
any deterioration in nonprotocol-required measurements of a laboratory value or other 
clinical test (eg, ECG or x-ray) that results in symptoms, a change in treatment, or 
discontinuation from study drug 
• 
recurrence of an intermittent medical condition (eg, headache) not present at baseline 
All AEs observed during the study will be reported on the eCRF.  All AEs, regardless of 
relationship to study drug or procedure, should be collected beginning from the time the subject 
signs the study ICF through the last subject contact.  Adverse events will be assessed during 
clinic visits. 
Every effort must be made by the Investigator to categorize each AE according to its severity and 
its relationship to the study treatment. 
 
Assessing Severity of Adverse Events 
Adverse events will be graded on a 5-point scale according to CTCAE v4.03 as follows: 
Grade 1 = 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
Grade 2 = 
Moderate; minimal, local, or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living 
Grade 3 = 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living 
Grade 4 = 
Life-threatening consequences; urgent intervention indicated 
Grade 5 = 
Death related to AE. 
Investigators will collect all CTCAE grades for AEs (for both increasing and decreasing severity).  
All AEs reported using CTCAE classification and graded as 4 or 5 are to be considered serious.  
The criteria for assessing severity are different from those used for seriousness (see Serious 
Adverse Events and Other Events of Interest for the definition of an SAE). 
 
Assessing Relationship of Adverse Events to Study Treatment 
Items to be considered when assessing the relationship of an AE to the study treatment are: 
• 
temporal relationship of the onset of the event to the initiation of the study treatment 
• 
the course of the event, especially the effect of discontinuation of study treatment or 
reintroduction of study treatment, as applicable 


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• 
whether the event is known to be associated with the study treatment or with other similar 
treatments 
• 
the presence of risk factors in the study subject known to increase the occurrence of the 
event 
• 
the presence of nonstudy, treatment-related factors that are known to be associated with the 
occurrence of the event  
 
Classification of Causality 
The relationship of each AE to the study drug will be recorded on the eCRF using the following 
criteria: 
Definitely Related:  A clinical event, including laboratory test abnormality, occurring in a plausible 
time relationship to drug administration, and which cannot be explained by concurrent or 
underlying disease or other drugs or conditions 
Probably Related:  A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the drug, unlikely to be attributed to concurrent or underlying 
disease or other drugs or conditions  
Possibly Related:  A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the drug, but which could also be explained by concurrent or 
underlying disease or other drugs or conditions 
Unlikely Related:  A clinical event, including laboratory test abnormality, with a temporal 
relationship to drug administration which makes a causal relationship improbable, and in which 
other drugs, conditions or concurrent or underlying disease provide plausible explanations. 
 Serious AEs and Other Events of Interest 
An SAE is any untoward medical occurrence that at any dose: 
• 
results in death 
• is life-threatening (ie, the subject was at immediate risk of death from the AE as it 
occurred; this does not include an event that, had it occurred in a more severe form or 
was allowed to continue, might have caused death) 
• requires inpatient hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity 
• 
is a congenital anomaly/birth defect (in the child of a subject who was exposed to the 
study drug) 
See Section 9.3.1 for SAE regulatory reporting requirements. 


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Other important medical events that may not be immediately life-threatening or result in death or 
hospitalization but, when based on appropriate medical judgment, may jeopardize the subject or 
may require intervention to prevent one of the outcomes in the definition of SAE listed above 
should also be considered SAEs.  Medical and scientific judgment should be exercised in deciding 
whether expedited reporting is appropriate in such situations. 
In addition to the above, other events of interest which include pregnancy, overdose, and 
treatment-emergent significant laboratory abnormality, are to be captured using the SAE 
procedures (see Section 9.3.3) but are to be considered as SAEs only if they meet one of the 
above criteria.  All AEs associated with events of interest are to be reported on the eCRF whether 
or not they meet the criteria for SAEs. 
The following hospitalizations are not considered to be SAEs because there is no “AE” (ie, there 
is no untoward medical occurrence) associated with the hospitalization: 
• planned hospitalizations required by the protocol 
• hospitalization planned before informed consent (where the condition requiring the 
hospitalization has not changed after study drug administration) 
 Laboratory Evaluations 
The Schedule of Procedures and Assessments (Table 6) show the visits at which blood and urine 
will be collected for clinical laboratory tests.  Collection of both blood and urine may be conducted 
at a local laboratory or at the clinic site.  Approximately 20 mL of blood will be collected for clinical 
laboratory (hematology and chemistry) testing (or approximately 10 mL for hematology testing 
alone) at Screening and Baseline within 96 hours prior to Week 1 Day 1 dosing, and within 48 
hours prior to Day 1 dosing at each subsequent designated week:  Chemistry will be tested at 
Weeks 1, 2, 4, 8, 12, and 16.  Hematology testing will be conducted weekly from Week 1 through 
Week 16.  Any additional hematology tests may be done at the discretion of the Investigator.  All 
hematology data obtained on subjects during this study will be included in the clinical database. 
Subjects must be fasted for the Screening/Baseline laboratory assessments.  It is recommended 
but not required, that subjects be fasted for the remaining weekly laboratory assessments.  It must 
be noted if subjects were in a fasted or fed state at the time of blood collection. 
Urinalysis will be conducted at Screening and Baseline within 96 hours prior to Week 1 Day 1 
dosing, and within 48 hours prior to Day 1 dosing at Weeks 4, 8, 12, and 16.  Microscopic 
urinalysis will be conducted only when clinically indicated based on dipstick results (laboratory 
protocol) or as determined by the Investigator.  When conducted, microscopic urinalysis will be 
recorded on the eCRF. 
Laboratory results must be reviewed and acceptable to the Investigator prior to dosing and 
following any treatment delays for unacceptable toxicity. 


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Serum pregnancy tests will be obtained in females of childbearing potential (ie, premenopausal 
women and postmenopausal women who have been amenorrheic for less than 12 months) at 
Screening/Baseline and every 8 weeks (Weeks 8 and 16).  A urine pregnancy test will be 
performed within 96 hours prior to Week 1, Day 1 dosing.  Test results must be reviewed prior to 
dosing.  Additional pregnancy testing will be performed as needed per local/country regulatory 
authority requirement. 
The clinical laboratory tests to be measured during the study are provided in Table 5. 
 
 


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A laboratory abnormality may meet the criteria to qualify as an AE as described in this protocol 
(see Adverse Events and Other Events of Interest) and the eCRF Completion Guidelines.  In 
these instances, the AE corresponding to the laboratory abnormality will be recorded on the 
Adverse Event eCRF. 
For laboratory abnormalities meeting the criteria of SAEs (see Serious Adverse Events and Other 
Events of Interest); the site must fax or send via email the SAE report including the laboratory 
report (if required by regional regulations) to the Sponsor using the SAE form (see Reporting of 
Serious Adverse Events [Section 9.3.1]). 
Table 5 
Clinical Laboratory Parameters 
Category 
Parameters 
Hematology 
red blood cells (RBC), hemoglobin, hematocrit, platelets, and white 
blood cells (WBC) with automated differential (neutrophils, 
lymphocytes, monocytes, eosinophils, basophils), mean corpuscular 
volume (MCV), mean corpuscular hemoglobin (MCH), mean 
corpuscular hemoglobin concentration (MCHC), RBC distribution 
width (RDW)a 
Chemistry 
Electrolytes 
sodium, potassium, chloride, bicarbonate (HCO3) 
Liver function tests 
alkaline phosphatase (ALP), aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), gamma-glutamyl transferase 
(GGT), total bilirubin, direct bilirubin 
Renal function parameter 
blood urea/blood urea nitrogen, creatinine  
Other 
glucose, calcium, magnesium, albumin, cholesterol, 
triglycerides, phosphorus, lactate dehydrogenase (LDH), 
total protein, uric acid, pregnancy testb 
Urinalysisc 
hydrogen ion concentration (pH), protein, glucose, ketones, occult 
blood, RBC, WBC, epithelial cells, bacteria, casts, crystals, 
specific gravity, pregnancy testb 
a. 
Some of the hematology parameters may not be collected, depending on the laboratory (eg, RDW). 
b. 
Pregnancy tests are performed with serum samples at scheduled assessments (Table 6), except for the timepoint 
of 96 hours prior to Week 1, Day 1 dosing, when a urine sample will be tested. 
c. 
Microscopic urinalysis will be conducted only when clinically indicated based on dipstick results (laboratory protocol) 
or as determined by the Investigator. 


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 Procedures to be Followed in the Event of Abnormal Laboratory Test 
Values or Abnormal Clinical Findings 
An abnormal laboratory test result should be considered as an AE if the identified laboratory 
abnormality leads to any type of intervention whether prescribed in the protocol or not. 
A treatment-emergent significant abnormal laboratory result should be considered by the 
Investigator to be an AE if it: 
• 
results in the withdrawal of study drug 
• 
results in withholding of study drug pending some investigational outcome 
• 
results in the initiation of an intervention, based on medical evaluation (eg, potassium 
supplement for hypokalemia) 
• 
results in any out of range laboratory value that in the Investigator’s judgment fulfills the 
definitions of an AE with regard to the subject’s medical profile 
• 
increases in severity compared with baseline by ≥2 CTCAE grades, with the exception 
of lymphocytes, albumin, cholesterol, glucose, and phosphate; for these tests, any 
change of ≥2 grades will be evaluated by the Investigator to determine if it is of clinical 
significance and, if so, will be considered an AE 
• 
is otherwise considered by the Investigator to meet serious criteria as defined in 
Section 9.2.2 (Serious Adverse Events and Other Events of Interest) 
Abnormal laboratory values should not be listed as separate AEs if they are considered to be part 
of the clinical syndrome that is being reported as an AE.  Any laboratory abnormality considered 
to constitute an AE should be reported on the Adverse Event eCRF. 
It is the responsibility of the Investigator to review all laboratory findings in all subjects and 
determine if they constitute an AE.  Medical and scientific judgment should be exercised in 
deciding whether an isolated laboratory abnormality should be classified as an AE. 
A laboratory result should be considered a treatment-emergent significant abnormality if the 
result: 
• increases in severity compared with baseline by ≥2 CTCAE grades, with the exception 
of lymphocytes, albumin, cholesterol, glucose, and phosphate; for these tests, any 
change of ≥2 grades will be evaluated by the Investigator to determine if it is of clinical 
significance and, if so, will be considered an AE 
• 
is otherwise considered by the Investigator to meet serious criteria as defined in 
Section 9.2.2 (Serious Adverse Events and Other Events of Interest) 


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 Electrocardiograms 
A 12-lead ECG is to be completed at Screening/Baseline and on Day 1 at Weeks 4, 8, 12, and 16 
(Table 6).  The Screening/Baseline ECG may be performed at a convenient time during the visit 
and 1 hour after Oraxol dosing on dosing days.  Subjects must be in the recumbent position for a 
period of 5 minutes prior to the ECG.  The ECG data recorded on the eCRF must include rate, 
rhythm, intervals, and QTc/QTcF. 
 Vital Signs  
Vital sign (pulse rate, systolic and diastolic blood pressure, respiratory rate, and body 
temperature) measurements will be taken after the subject has been seated for at least 5 minutes 
at Screening/Baseline, prior to dosing Day 1 of Weeks 1, 2, 3, 4, 8, 12, and 16, and at the Final 
Visit (Table 6).  All blood pressure measurements should be performed on the same arm, 
preferably by the same person at the designated visits.  Serial vital signs may be obtained to 
confirm accurate readings. 
 Physical Examinations 
Complete physical examinations will be performed at Screening/Baseline and every 8 weeks, 
(Weeks 8 and 16) (Table 6). 
A complete physical examination will include weight and an assessment of head, eyes, ears, 
nose, and throat (HEENT), GI, cardiovascular, respiratory, integumentary, muscular-skeleton, 
and neurological systems.  Height will only be measured and recorded at Screening/Baseline. 
Documentation of the physical examination will be included in the source documentation at the 
site.  Only changes from screening/baseline physical examination findings that meet the definition 
of an AE will be recorded on the Adverse Events eCRF. 
 Concomitant Medications 
The subject’s concomitant medications will be assessed and recorded at all clinic visits.  In 
between clinic visits, subjects will be instructed to call designated study personnel if they 
experience any AEs and/or associated concomitant medications taken (Table 6). 
 
Reporting Procedures 
Adverse events will be reported from the time of consent through the last subject contact. 
Adverse events will be reported by the Sponsor or a third party acting on behalf of the Sponsor to 
regulatory authorities in compliance with local and regional law and established guidance.  The 
format of these reports will be dictated by the local and regional requirements. 


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Serious Adverse Events 
Serious AEs will be reported from the time of signing informed consent through the last subject 
contact; in addition, any SAEs that are reported to the Investigator in the 30 days following the 
last subject contact are also reported. 
Serious AEs reported at any time following the subjects’ participation in the study must be 
reported, if, in the opinion of the Investigator, they are possibly related to study treatment, 
regardless of the amount of time that may have elapsed since the end of the study. 
All SERIOUS ADVERSE EVENTS, regardless of their relationship to study treatment, must 
be reported on a completed SAE form by email or fax as soon as possible but no later than 
1 business day from the date the Investigator becomes aware of the event. 
Deaths and life-threatening events should be reported immediately by telephone.  The 
immediate report should be followed up within 1 business day by emailing or faxing the 
completed SAE form. 
Detailed contact information for reporting of SAEs will be provided in the Investigator Study File. 
It is very important that the SAE report form be filled out as completely as possible at the time of 
the initial report.  This includes the Investigator’s assessment of causality. 
Any follow-up information received on SAEs should be forwarded within 1 business day of its 
receipt.  If the follow-up information changes the Investigator’s assessment of causality, this 
should also be noted on the follow-up SAE form. 
Preliminary SAE reports should be followed as soon as possible by detailed descriptions including 
copies of hospital case reports, autopsy reports, and other documents requested by the Sponsor. 
Regulatory Reporting 
The Sponsor must inform Investigators (or as regionally required, the head of the medical 
institution) and regulatory authorities of reportable events, in compliance with applicable 
regulatory requirements, on an expedited basis (ie, within specific timeframes).  For this reason, 
it is imperative that sites provide complete SAE information in the manner described above. 
Other Adverse Events 
Reporting of Overdose 
Study drug overdose is defined as the accidental or intentional use of the study drug in an amount 
higher than the dose being studied. 


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Any study drug overdose during the study should be noted on the Study Medication eCRF. 
All AEs associated with an overdose should be entered both on the Adverse Event eCRF and 
reported using the procedures detailed in reporting of Serious Adverse Events (Section 9.3.1) 
even if the events do not meet serious criteria.  If the AE associated with an overdose does not 
meet serious criteria, it must still be reported using the SAE form and in an expedited manner but 
should be noted as nonserious on the SAE form and the Adverse Event eCRF. 
 
Reporting of Significant Laboratory Abnormality 
Only treatment-emergent significant laboratory abnormalities are required to be reported.  
Treatment-emergent significant laboratory abnormalities are those which occur following the first 
dose of study medication up through 30 days following last subject contact. 
A laboratory result should be considered a treatment-emergent significant abnormality if the result 
meets the criteria described in Section 9.2.4. 
Any treatment-emergent significant laboratory abnormality observed during the clinical study 
should be entered on the Adverse Event eCRF and reported using the procedures detailed in 
Section 9.3.1, even if the laboratory abnormality does not meet serious criteria.  If the significant 
laboratory abnormality does not meet serious criteria, it must still be reported using the SAE form 
and in an expedited manner but should be noted as nonserious on the SAE form and the Adverse 
Event eCRF. 
 
Reporting of Pregnancy 
Any pregnancy, whether occurring in a subject or in the female partner of a male subject, for which 
the estimated date of conception falls within either of the following timeframes must be reported: 
• 
anytime from signing informed consent until 30 days after last study treatment, or  
• 
any exposure to study drug through breastfeeding during study treatment or within 30 days 
after last study treatment 
If an adverse outcome of a pregnancy is suspected to be related to study drug exposure, this 
should be reported regardless of the length of time that has passed since the exposure to study 
treatment. 
A congenital anomaly, death during perinatal period, an induced abortion, or a spontaneous 
abortion are considered to be an SAE and should be reported in the same timeframe and in the 
same format as all other SAEs (Section 9.3.1). 
Pregnancies or exposure to study drug through breastfeeding must be reported by fax or email 
as soon as possible but no later than 1 business day from the date the Investigator becomes 
aware of the pregnancy.  The contact information for the reporting of pregnancies and exposure 
to study drug through breastfeeding is provided in the Investigator Study File.  The Pregnancy 


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Report Form must be used for reporting.  All pregnancies must be followed to outcome.  The 
outcome of the pregnancy must be reported as soon as possible but no later than 1 business day 
from the date the Investigator becomes aware of the outcome. 
A subject who becomes pregnant must be withdrawn from the study.  If the female partner of a 
male subject becomes pregnant, that male subject also needs to be withdrawn from the study. 
 
Type and Duration of Follow-up of Subjects after Adverse 
Events 
Subjects with onset of study drug-related AEs will be followed until resolution, resolved with 
sequelae, or the subject is under medical care.   
All SAEs must be followed to resolution or, if resolution is unlikely, to stabilization. 


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CLINICAL MONITORING 
 Site Monitoring Plan 
The Sponsor’s/ contract research organization’s (CRO’s) contract research associate (CRA) will 
maintain contact with the Investigator and designated staff by telephone, letter, or email between 
study visits.  Monitoring visits to each site will be conducted by the assigned CRA as described in 
the monitoring plan.  The Investigator (or if regionally required, the head of the medical institution) 
will allow the CRA to inspect the clinical, laboratory, and pharmacy facilities to assure compliance 
with GCP and local regulatory requirements.  The eCRFs and subject’s corresponding original 
medical records (source documents) are to be fully available for review by the sponsor’s 
representatives at regular intervals.  These reviews verify adherence to study protocol and data 
accuracy in accordance with local regulations.  All records at the site are subject to inspection by 
the local auditing agency and to IRB/IEC review. 
In accordance with International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH) E64, Section 1.52, source documents 
include, but are not limited to, the following: 
• 
clinic, office, or hospital charts 
• 
copies or transcribed health care provider notes that have been certified for accuracy 
after production 
• 
recorded data from automated instruments such as IxRS, x-rays, and other imaging 
reports (eg, sonograms, CT scans, MRIs, radioactive images, ECGs, rhythm strips, 
EEGs, polysomnographs, pulmonary function tests) regardless of how these images are 
stored, including microfiche and photographic negatives 
• 
pain, quality of life, or medical history questionnaires completed by subjects 
• 
records of telephone contacts 
• 
diaries or evaluation checklists 
• 
drug distribution and accountability logs maintained in pharmacies or by research 
personnel 
• 
laboratory results and other laboratory test outputs (eg, urine pregnancy test result 
documentation and urine dip-sticks) 
• 
correspondence regarding a study subject’s treatment between physicians or 
memoranda sent to the IRBs/IECs 
• 
CRF components (eg, questionnaires) that are completed directly by subjects and serve 
as their own source 


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STATISTICAL CONSIDERATIONS 
All statistical analyses will be performed by the Sponsor or designee after the study is completed 
and the database is locked and released.  Statistical analyses will be performed using SAS 
software or other validated statistical software as required.  Details of the statistical analyses will 
be included in a separate statistical analysis plan (SAP). 
A total of 24 evaluable subjects receiving Oraxol will be analyzed.  Subjects who do not have 
Week 4 PK assessments for any reason will be replaced. 
Statistical analyses will be reported using summary tables, graphs, and data listings. Continuous 
variables will be summarized using the mean, standard deviation, median, minimum, and 
maximum.  Categorical variables will be summarized by counts and by percentage of subjects in 
corresponding categories.  All raw data obtained from the eCRF as well as any derived data will 
be included in data listings. 
The statistical analyses of study data are described in this section.  Further details of the analytical 
plan will be provided in the SAP, which will be finalized before database lock. 
The definitions of the Analysis Sets which will be used in the study are as follows: 
Safety/Full Analysis Set:  The Safety population / Full Analysis Set will include all subjects who 
receive at least 1 dose of study treatment. 
Evaluable Set: The Evaluable population will include all protocol-eligible subjects who receive at 
least 1 dose of study treatment and have at least 1 post-treatment PK evaluation. 
 Study Hypotheses 
This is a PK study with a single treatment arm.  No statistical tests will be applied to the primary 
endpoints.  For the secondary activity endpoint tumor response rate, its 95% CI will be evaluated 
per a binomial test. 
 Planned Interim Analyses 
None 


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 Pharmacokinetic Analyses 
 Calculation of Noncompartmental Pharmacokinetic Parameters 
Plasma concentrations for paclitaxel only will be analyzed to determine the following PK 
parameters:  Cmax, Cmin, Cavg, AUC0-t, and AUCτ. 
Pharmacokinetic parameters will be summarized using the mean, standard deviation, median, 
minimum, and maximum.  Summaries of PK parameters will also include the geometric mean 
and the coefficient of variation. 
Summary PK and individual timepoints will be tabulated and displayed graphically and listed for 
all subjects. 
11.3.2 Population Pharmacokinetic Analysis 
Using the PK samples collected at designated timepoints, a population PK analysis will be 
explored and then used to estimate individual AUCs or clearance (CL) of paclitaxel.  The effect of 
patient factors on paclitaxel PK will be explored that may explain interpatient variability in PK 
parameters.  Both inter- and intra-patient variability in paclitaxel AUC will also be assessed.  
Paclitaxel AUC, as well as Cmax, will then be tested for association of changes with toxicity 
endpoints, such as neutropenia or incidence of neuropathy.  If an observable trend exists among 
changes in any of these AEs, a pharmacokinetic/pharmacodynamic (PK/PD) model will be 
developed to evaluate the exposure-response relationship between the time course of paclitaxel 
plasma exposure (eg, AUC, Cmax) in relation to changes in neutropenia and/or neuropathy.  
Demographic and clinical data (ie, ethnicity, age, BSA, ECOG performance status, etc) will be 
utilized to assess interpatient variability in the model.  
Time to maximum concentration (Tmax) and other summary PK and individual timepoints will be 
tabulated and displayed graphically and listed for all subjects. 
 Safety Analyses 
 Extent of Exposure 
The actual number of doses will be summarized by visit. 
 Adverse Events 
For AEs, verbatim terms on the eCRF will be mapped to preferred terms (PTs) and system organ 
classes (SOCs) using the Medical Dictionary for Regulatory Activities (MedDRA; version 16.0 or 
higher).  The CTCAE criteria v4.03 will be used to grade severity of the AEs.  Subject incidence 
of AEs will be displayed by SOC.  The incidence of AEs will be summarized.  Adverse events will 


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also be summarized by severity and relationship to study drug.  Subject incidence of SAEs will be 
displayed. 
For analysis purposes, a TEAE is defined as an AE that emerges after the first dose of study 
treatment, having been absent at pretreatment (Baseline) or 
• 
re-emerges after the first dose of study treatment, having been present at Baseline but 
stopped prior to treatment, or 
• 
worsens in severity after the first dose of study treatment relative to the pretreatment state, 
when the AE is continuous 
Only those AEs that were treatment emergent will be included in summary tables.  All AEs, 
treatment emergent or otherwise, will be presented in subject data listings.  
Treatment-emergent AEs will be summarized.  The incidence of TEAEs will be reported as the 
number (percentage) of subjects with TEAEs by SOC and PT.  Subjects will be counted only once 
within a SOC and PT, even if the subject experienced more than one TEAE within a specific SOC 
and PT.  The number (percentage) of subjects with TEAEs will also be summarized by 
seriousness, maximum severity (highest CTCAE grade), outcome, action taken with IP, other 
treatment given, relationship to the IP, and relationship to progression of disease. 
The number (percentage) of subjects with TEAEs leading to death will be summarized by 
MedDRA SOC and PT.  A subject data listing of all AEs leading to death will be provided. 
The number (percentage) of subjects with TEAEs leading to discontinuation from study drug will 
be summarized by MedDRA SOC and PT.  A subject data listing of all AEs leading to 
discontinuation from study drug will be provided. 
 Laboratory Values 
Laboratory parameters will be summarized using descriptive statistics at baseline and at each 
subsequent time-point.  Changes from baseline will also be summarized.  Treatment-emergent 
significant abnormalities (as defined in Section 9.2.4) will be summarized. 
 Vital Signs 
Vital sign values will be evaluated on an individual basis by subject.  Abnormal vital sign values 
will be identified as those outside (above or below) the reference range. 
 Other Special Tests 
Eastern Cooperative Oncology Group performance status will be summarized. 


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 Activity Analyses 
Tumor response rate and its 95% CI will be evaluated based on the number of subjects with any 
postbaseline CR or PR per RECIST criteria both as evaluated by investigator and by central 
radiology review committee.5  In addition, the incidence of tumor response at each clinical visit 
will be summarized. 
Progression-free survival and overall survival will be estimated.  PFS is defined as the 
time from the first dose of study drug in study KX-ORAX-007 to the time of documented 
disease progression or death. OS is defined as the time from the first dose of study drug 
in study KX-ORAX-007 to date of death. 
 Final Analysis Plan 
The final analysis plan will be presented in the SAP, including procedures for accounting for 
missing, unused, and spurious data. 
The SAP will be issued prior to database lock and final analyses and will include plans for any 
exploratory analyses, as well as any changes in the other statistical analyses. 
If the prespecified plans need to be revised after the study starts, the Sponsor will determine how 
the revision impacts the study and how the revision should be implemented.  The details of the 
revision will be documented and described in the clinical study report. 


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SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
All data to be recorded on the eCRF must reflect the corresponding source documents. 


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QUALITY CONTROL AND QUALITY ASSURANCE 
 Auditing Procedures and Inspection 
In addition to routine monitoring procedures, the Sponsor’s Clinical Quality Assurance department 
(or designee) conducts audits of clinical research activities in accordance with the sponsor’s 
SOPs to evaluate compliance with the principles of ICH GCP and all applicable local regulations.  
If a government regulatory authority requests an inspection during the study or after its 
completion, the Investigator must inform the Sponsor immediately. 
 Database Quality Assurance 
All software applications used in the collection of data will be properly validated following standard 
computer system validation that is compliant with all regulatory requirements.  Validation 
requirements will be documented in the Data Management Plan. 


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ETHICS/PROTECTION OF HUMAN SUBJECTS 
 Ethical Standard 
This study will be conducted in accordance with SOPs of the Sponsor (or designee), which are 
designed to ensure adherence to the requirements and principles of ICH GCP guidelines (ICH - 
E6 Guideline for GCP Harmonised Tripartite Guideline)4, the World Medical Association 
Declaration of Helsinki 2013, and other applicable national or local regulations.  All required study 
documentation will be archived as required by regulatory authorities. 
 Institutional Review Board/Independent Ethics Committee 
The protocol, any protocol amendments, and the ICF will be reviewed and approved by an 
IRB/IEC constituted and functioning in accordance with ICH E6, Section 3, and any local 
regulations of the national authority before subjects are screened for entry.  Any protocol 
amendment and/or revision to the ICF will receive appropriate approval prior to implementation.  
Verification of unconditional approval of the protocol will be transmitted to the Sponsor prior to the 
shipment of drug supplies to the investigational site.  The Investigators or the Sponsor will submit, 
depending on local regulations, periodic reports and inform the IRB/IEC of any reportable AEs 
per ICH guidelines and local IRB/IEC standards of practice. 
 Informed Consent Process 
The Investigator or the Investigator’s staff will obtain written consent directly from subjects prior 
to the screening examination.  After giving informed consent, each subject will be registered and 
assigned a subject number, which will be recorded.  The Investigator or the Investigator’s staff 
will record the subject number (3-digit trial site number + 4-digit sequential serial number) and the 
date of written informed consent on the medical records and eCRF. 
 Subject Confidentiality 
The contents of this protocol and any amendments and results obtained during the study should 
be kept confidential by the Investigator, the Investigator’s staff, and the IRB/IEC and will not be 
disclosed in whole or in part to others, or used for any purpose other than reviewing or performing 
the study, without the written consent of the Sponsor.  No data collected as part of this study will 
be used in any written work, including publications, without the written consent of the Sponsor.  
These obligations of confidentiality and non-use shall in no way diminish such obligations as set 
forth in either the Confidentiality Agreement or Clinical Trial Agreement executed between the 
Sponsor/CRO and the institution/Investigator. 


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All persons assisting in the performance of this study must be bound by the obligations of 
confidentiality and non-use set forth in either the Confidentiality Agreement or Clinical Trial 
Agreement executed between the institution/Investigator and the Sponsor/CRO. 
 Future Use of Stored Specimens 
Residual PK samples will be stored until regulatory approval of the IP, at which point the 
specimens will be destroyed. 
 Subject Insurance and Indemnity 
The Sponsor will provide insurance for any subjects participating in the study in accordance with 
all applicable laws and regulations. 


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DATA HANDLING AND RECORD KEEPING 
An eCRF is required and must be completed for each subject by qualified and authorized 
personnel.  All data on the eCRF must reflect the corresponding source document, except when 
a section of the eCRF itself is used as the source document.  Any correction to entries made on 
the eCRF must be documented in a valid audit trail where the correction is dated, the individual 
making the correct is identified, the reason for the change is stated, and the original data are not 
obscured.  Only data required by the protocol for the purposes of the study should be collected. 
The Investigator must sign each eCRF.  The Investigator will provide the eCRFs to the Sponsor 
and retain a copy of the eCRFs. 
 Data Management Responsibilities 
Data required by the protocol will be collected on the eCRFs and entered into a validated data 
management system that is compliant with all regulatory requirements.  As defined by ICH 
guidelines, the CRF is a printed, optical, or electronic document designed to record all of the 
protocol-required information to be reported to the Sponsor on each study subject. 
Data collection on the CRF must follow the instructions described in the CRF Completion 
Guidelines.  The Investigator has ultimate responsibility for the collection and reporting of all 
clinical data entered on the CRF.  The Investigator or must sign the completed CRF to attest to 
its accuracy, authenticity, and completeness. 
Completed, original CRFs are the sole property of the Sponsor and should not be made available 
in any form to third parties without written permission from the Sponsor, except for authorized 
representatives of the Sponsor or appropriate regulatory authorities. 
 Data Capture Methods 
All data, both eCRF and external data (eg, laboratory data), will be entered into a clinical system. 
Quality control and data validation procedures will be applied to ensure the validity and accuracy 
of the clinical data. 
 Types of Data 
Data for this study will include PK, safety, laboratory, and outcome measures. 


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 Study Records Retention 
The circumstances of completion or termination of the study notwithstanding, the Investigator (or 
if regionally required, the head of the medical institution or the designated representative) is 
responsible for retaining all study documents, including but not limited to the protocol, copies of 
CRFs, the Investigator's Brochure, and regulatory agency registration documents (eg, ICFs and 
IRB/IEC correspondence).  The site should plan to retain study documents, as directed by the 
Sponsor, for at least 2 years after the last approval of a marketing application in an ICH region 
and until there are no pending or contemplated marketing applications in an ICH region or at least 
3 years have elapsed since the formal discontinuation of clinical development of the IP. 
It is requested that at the completion of the required retention period, or should the Investigator 
retire or relocate, the Investigator contact the Sponsor, allowing the Sponsor the option of 
permanently retaining the study records. 
 Protocol Deviations 
The Investigator will conduct the study in strict accordance with the protocol (refer to ICH E6, 
Section 4.5). 
There are to be no changes to the protocol without written approval from the Sponsor.  Protocols 
will be followed as written. 
Any change to the protocol requires a written protocol amendment that must be approved by the 
Sponsor before implementation.  Amendments specifically affecting the safety of subjects, the 
scope of the investigation, or the scientific quality of the study require submission to health or 
regulatory authorities as well as additional approval by the applicable IRBs/IECs.  These 
requirements should in no way prevent any immediate action from being taken by the Investigator, 
or by the Sponsor, in the interest of preserving the safety of all subjects included in the study.  If 
the Investigator determines that an immediate change to or deviation from the protocol is 
necessary for safety reasons to eliminate an immediate hazard to the subjects, the Sponsor’s 
medical monitor (or appropriate team member) and the IRB/IEC for the site must be notified 
immediately.  The Sponsor must notify the health or regulatory authority as required per local 
regulations. 


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PUBLICATION POLICY 
All manuscripts, abstracts, or other modes of presentation arising from the results of the study 
must be reviewed and approved in writing by the Sponsor in advance of submission pursuant to 
the terms and conditions set forth in the executed Clinical Trial Agreement between the 
Sponsor/CRO and the institution/Investigator.  The review is aimed at protecting the Sponsor's 
proprietary information existing either at the date of the commencement of the study or generated 
during the study. 
The detailed obligations regarding the publication of any data, material results, or other 
information generated or created in relation to the study shall be set out in the agreement between 
each Investigator and the Sponsor or CRO, as appropriate. 


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LITERATURE REFERENCES 
1.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al.  New
response evaluation criteria in solid tumours:  Revised RECIST guideline (version 1.1).
Eur J Cancer. 2009;45:228-47.
2.
Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events
(CTCAE) version 4.0 [published 28 May 2009 (v4.03: June 14, 2010)].  Available from:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf
3.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al.  Toxicity and
Response Criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.
1982;5:649-655.  Courtesy of Eastern Cooperative Oncology Group, Robert Comis M.D.,
Group 
Chair. 
http://ecog-acrin.org/resources/ecog-performance-status. 
Accessed
September 2015.
4.
ICH E6: Guidance for Industry - E6 Good Clinical Practice: Consolidated Guidance, US 
Department of Health and Human Services, Food and Drug Administration, April 1996. 
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm073122.pdf
5.
Guidance for Industry; Clinical Trial Endpoints for the Approval of Cancer Drugs and
Biologics. May 2007.


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SUPPLEMENTS/APPENDICES 
 


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APPENDIX A:  SCHEDULE OF EVENTS 
Table 6 
Schedule of Procedures and Assessments in KX-ORAX-007 
Period 
Screen
-inga / 
Base-
line 
Treatment 
FUb 
Week 
 
Week 1 
Wk 2 
Wk 3 
Wk 4 
Wks 
5/6/7 
Wk 8 
Wks 
9/10/11 
Wk 12 
Wks 
13/14/15 
Wk 16 
Within 
7 days 
Day 
-28 to 
 -1 
1 
2 
3 
1 
1 
1 
2 
3 
1 
1 
1 
1 
1 
1 
 
Visit Window 
 
 
 
 
±1 day 
±1 day 
±1 day 
 
 
±2 days 
±2 days 
±2 days 
±2 days 
±2 days 
±2 
days 
 
Clinic Visitc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/surgical/ 
oncologic historyd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
Xe 
Xe 
Pregnancy testf 
Xf 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
ECGg 
X 
 
 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
ECOG PS 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examh 
Xi 
 
 
 
 
 
 
 
 
 
Xh 
 
 
 
Xh 
 
Vital signs 
X 
X 
 
 
X 
X 
X 
 
 
 
X 
 
X 
 
X 
X 
PK samplingj 
 
X 
X 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
 
Oraxol treatmentk 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dispense Oraxol 
 
 
 
 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Lab tests (UA)l 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
Lab tests 
(chemistry)l 
X 
Xl 
 
 
X 
 
X 
 
 
 
X 
 
X 
 
X 
 
Lab tests 
(hematology)l, m 
X 
Xl 
 
 
Xm 
Xm 
Xm 
 
 
Xm 
Xm 
Xm 
Xm 
Xm 
Xm 
 
Imaging (CT/MRI)n 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Tumor 
assessmentso 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 


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Table 6 
Schedule of Procedures and Assessments in KX-ORAX-007 
Period 
Screen
-inga / 
Base-
line 
Treatment 
FUb 
Week 
 
Week 1 
Wk 2 
Wk 3 
Wk 4 
Wks 
5/6/7 
Wk 8 
Wks 
9/10/11 
Wk 12 
Wks 
13/14/15 
Wk 16 
Within 
7 days 
Day 
-28 to 
 -1 
1 
2 
3 
1 
1 
1 
2 
3 
1 
1 
1 
1 
1 
1 
 
Visit Window 
 
 
 
 
±1 day 
±1 day 
±1 day 
 
 
±2 days 
±2 days 
±2 days 
±2 days 
±2 days 
±2 
days 
 
Clinic Visitc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse eventsp 
X 
X 
BSA = body surface area; CT = computed tomography; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group Performance Status; FU =follow-up; HEENT = head, 
eyes, ears, nose, and throat; IP = investigational product; MRI = magnetic resonance imaging; PE = physical examination; PK = pharmacokinetic; RECIST = Response Evaluation Criteria 
in Solid Tumors; UA = urinalysis; Wk = Week. 
a. Subjects must be screened within 28 days prior to Week 1, Day 1 dosing. 
b. Subjects are to be followed-up for safety at a Final Visit, within 7 days after last dose of study treatment.  After completion of Final Visit assessments, subjects will be contacted every 
2 months to follow progression-free survival and overall survival. New anti-cancer therapy will be collected. 
c. Unscheduled visits will occur only at the discretion of the Investigator.  Results of any assessments performed at unscheduled visits will be entered into the clinical database. 
d. A complete oncology history includes all malignancies prior to Screening, regardless of diagnosis date or status, eg, skin cancer. 
e. At Screening/Baseline, includes a complete oncology treatment history which includes all commercial products and IPs, radiation, and other prescribed and over the counter therapies 
dating back to the initial diagnosis.  Concomitant medications will be assessed and recorded at all clinic visits.  In between clinic visits, subjects will be instructed to call designated study 
personnel if they experience any AEs and/or associated concomitant medications taken. 
f. Serum pregnancy tests will be obtained at Screening/Baseline and every 8 weeks (Weeks 8 and 16).  Urine pregnancy test will be performed within 96 hours prior to Week 1, Day 1 
dosing.  Test results must be reviewed prior to dosing.   
g. ECGs will be performed at Screening/Baseline, and on Day 1 at Weeks 4, 8, 12, 16.  ECGs will be performed at a convenient time at Screening/Baseline and 1 hour after Oraxol dosing 
on dosing days. 
h. Physical exam will include body weight and at Screening/Baseline only, height.  Complete physical examinations will be performed at Screening/Baseline and every 8 weeks, (Weeks 8 
and 16).  A complete PE will include an assessment of HEENT, gastrointestinal, cardiovascular, respiratory, integumentary, muscular-skeleton, and neurological systems. 
i. BSA will be estimated based on baseline body weight and height and will be calculated at Baseline.  Following dose calculation at baseline, BSA will be used to recalculate the dose for 
dose reduction, if needed, after an unacceptable toxicity. 
j. Subjects will be housed in the clinic from the night before dosing on Week 1, Day 1 and Week 4, Day 1 through the end of PK sampling on Day 3.  See Table 3 and Table 4 for PK 
sampling timepoints.   
k. Oraxol will be administered on Days 1-3 of each week, up to 16 weeks.  During PK sampling days, Oraxol will be administered to the subject in the clinic on scheduled dosing days.  
Subjects will be given information cards on which they will record their dosing information. 
l. Clinical laboratory tests will be conducted at Screening and Baseline within 96 hours prior to Week 1 Day 1 dosing, and within 48 hours prior to Day 1 dosing of each subsequent 
designated week.  See Section 9.2.3 for the frequency of laboratory testing and Table 5 for a listing of the hematology, chemistry, and urine tests to be performed.  Subjects must be fasted 
for the Screening/Baseline laboratory assessments.  Fasting is recommended, but not required, at other laboratory assessment times.  Collection of both blood and urine may be conducted 
at a local laboratory or at the clinic site. 


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Table 6 
Schedule of Procedures and Assessments in KX-ORAX-007 
Period 
Screen
-inga / 
Base-
line 
Treatment 
FUb 
Week 
 
Week 1 
Wk 2 
Wk 3 
Wk 4 
Wks 
5/6/7 
Wk 8 
Wks 
9/10/11 
Wk 12 
Wks 
13/14/15 
Wk 16 
Within 
7 days 
Day 
-28 to 
 -1 
1 
2 
3 
1 
1 
1 
2 
3 
1 
1 
1 
1 
1 
1 
 
Visit Window 
 
 
 
 
±1 day 
±1 day 
±1 day 
 
 
±2 days 
±2 days 
±2 days 
±2 days 
±2 days 
±2 
days 
 
Clinic Visitc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
m. Clinical hematology laboratory tests will be conducted weekly within 48 hours before Day 1 dosing of Weeks 2 through 16.  Additional hematology tests may be done at the discretion of 
the Investigator.  Collection of blood may be conducted at a local laboratory or at the clinic site.  All hematology data obtained will be included in the clinical database.  
n. During the Screening/Baseline Period, a baseline CT/MRI scan will be conducted before the first dose on Week 1, Day 1 of Oraxol treatment, as close to Day 1 as possible.  Subsequent 
scans will be conducted every 8 weeks (at Weeks 8 and 16) until documented progression.  Unscheduled scans should be conducted, if clinically indicated, per the discretion of the 
Investigator.  Results of these unscheduled scans will be entered into the clinical database. 
o. Based on RECIST v1.1 criteria. 
p. Any adverse events that occur after signing the informed consent.  Adverse events will be assessed and recorded at all clinic visits.  In between clinic visits, subjects will be instructed to 
call designated study personnel if they experience any adverse events. 


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APPENDIX B:  ECOG PERFORMANCE STATUS 
Grade 
Status 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, eg, light house work, office work 
2 
Ambulatory and capable of all self-care, but unable to carry out any work 
activities; up and about more than 50% of waking hours 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or 
chair 
5 
Dead 
ECOG = Eastern Cooperative Oncology Group. 
Adapted from Oken MM et al. Am J Clin Oncol. 1982;5:649-5. 
 
 


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