Clinical Trials Register

Summary
EudraCT Number:	2015-001526-42
Sponsor's Protocol Code Number:	GS-US-296-1080
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-02-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2015-001526-42

A.3

Full title of the trial

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-5745 Combined with mFOLFOX6 as First Line Treatment in Patients with Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Clinical Study to evaluate the efficacy and safety of GS-5745 in combination with standard of care in patients with stomach cancer.

A.4.1

Sponsor's protocol code number

GS-US-296-1080

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02545504

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Gilead Sciences, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Gilead Sciences, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gilead Sciences International Ltd.
B.5.2	Functional name of contact point	Clinical Trials Mailbox
B.5.3	Address:
B.5.3.1	Street Address	Flowers Building, Granta Park
B.5.3.2	Town/ city	Abington, Cambridge
B.5.3.3	Post code	CB21 6GT
B.5.3.4	Country	United Kingdom
B.5.5	Fax number	+441223897284
B.5.6	E-mail	clinical.trials@gilead.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	GS-5745
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GS-5745
D.3.9.2	Current sponsor code	GS-5745
D.3.9.3	Other descriptive name	GS-5745
D.3.9.4	EV Substance Code	SUB119675
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

E.1.1.1

Medical condition in easily understood language

advanced stomach cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10066354
E.1.2	Term	Adenocarcinoma of the gastroesophageal junction
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10071114
E.1.2	Term	Metastatic gastric adenocarcinoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the efficacy of GS-5745 versus placebo in combination with mFOLFOX6 as measured by overall survival (OS)

E.2.2

Secondary objectives of the trial

To compare the efficacy of GS-5745 versus placebo in combination with mFOLFOX6 as measured by progression-free survival (PFS)

To compare the efficacy of GS-5745 versus placebo in combination with mFOLFOX6 as measured by objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)

To compare the safety of GS-5745 versus placebo in combination with mFOLFOX6

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible
for participation in this study:

1) Male or female more than but equal to 18 years of age
2) Histologically confirmed adenocarcinoma of the stomach or GEJ
with inoperable, locally advanced or metastatic disease, not
amenable to curative therapy

Adenocarcinoma of the GEJ is defined as tumors that have their
center within 5 cm proximal and distal of the anatomical
esophago-gastric junction as described in Siewert’s classification
system

3) Eastern Cooperative Oncology Group (ECOG) ≤ 1

4) Measurable disease or non-measurable but evaluable disease,
according to RECIST v1.1. Subjects with peritoneal disease would
generally be regarded as having evaluable disease and allowed to
enter the trial

5) Subjects not receiving anticoagulant medication must have an
international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 X upper limit of normal (ULN)
The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the
medical standard in the institution) and the subject has been on stable dose of anticoagulants for at least 1 week at the time of randomization.

6) Adequate hematologic function:

a) neutrophils more than but equal to 2.0 x 10 power 9/L
b) platelets more than but equal to 100 x 10 power 9/L
c) hemoglobin more than but equal to 9 g/dL

7) Adequate hepatic function:
a) Direct or total bilirubin less than equal to 1.5 x ULN
b) ALT and AST less than but equal to 2.5 x ULN, in case of liver metastases
≤ 5 x ULN
8) Creatinine clearance (CLcr) should be ≥ 30 mL/min based on the
Cockroft-Gault formula. Subjects with a CLcr just below
30 mL/min may be eligible if a measured creatinine clearance
(based on 24 hour urine collection or other reliable method) is
≥ 30 mL/min
9) For female subjects of childbearing potential, willingness to use a
protocol-recommended method of contraception from the
screening visit throughout the study treatment period, for 90 days
following the last dose of study drug (GS-5745/placebo), and for 4 months after the last
dose of oxaliplatin or 6 months after the last dose of 5-FU whichever occurs later, unless the subject chooses
continuous heterosexual abstinence as a lifestyle-choice.

10) For male subjects of reproductive potential having intercourse with
females of childbearing potential, willingness to use a protocol
recommended method of contraception and to refrain from sperm
donation from the start of study drug, throughout the study
treatment period, for 90 days after administration of the last dose of
any study drug, and for 6 months after the last dose of oxaliplatin or 6 months following the last dose of 5-FU whichever occurs later

11) Breastfeeding females must agree to discontinue nursing before
study drug administration

12) In the judgment of the investigator, participation in the protocol
offers an acceptable benefit-to-risk ratio when considering current
disease status, medical condition, and the potential benefits and
risks of alternative treatments for the subject’s cancer

13) Willingness to comply with scheduled visits, drug administration
plan, imaging studies, laboratory tests, other study procedures, and
study restrictions

14) Evidence of a signed informed consent prior to implementation of
any protocol specific procedure

E.4

Principal exclusion criteria

Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be
randomized in this study:
1) Previous chemotherapy for locally advanced or metastatic gastric
or GEJ cancer. Subjects may have received prior neoadjuvant or
adjuvant chemotherapy as long as it was completed at least
6 months prior to randomization
2) Human Epidermal Growth Factor Receptor 2 (HER2) cancer
(primary tumor or metastatic lesion). HER2-positivity is defined as
either IHC3+ or IHC2+/ISH+ (ISH positivity is defined as a
HER2:CEP17 ratio of ≥2.0.)
3) Patients who have received palliative radiation and have not
recovered from all acute, reversible effects
4) Uncontrolled intercurrent illness including, but not limited to,
active uncontrolled infection, active gastrointestinal bleeding,
uncontrolled cardiac arrhythmia, or psychiatric illness/social
situation that would limit compliance with study requirements as
judged by treating physician
5) History of a concurrent or second malignancy except for
adequately treated local basal cell or squamous cell carcinoma of
the skin, cervical carcinoma in situ, superficial bladder cancer,
asymptomatic prostate cancer without known metastatic disease
and with no requirement for therapy or requiring only hormonal
therapy and with normal prostate-specific antigen for ≥ 1 year prior
to randomization, adequately treated Stage 1 or 2 cancer currently
in complete remission, or any other cancer that has been in
complete remission for ≥ 5 years

6) Major surgery, defined as any surgical procedure that involves
general anesthesia and a significant incision (ie, larger than what is
required for placement of central venous access, percutaneous
feeding tube, or biopsy), within 28 days of first dose of study drug

7) Known positive status for human immunodeficiency virus (HIV)
8) Known acute or chronic-active infection with hepatitis B virus
(HBV) or hepatitis C virus (HCV)
9) Peripheral neuropathy ≥ Grade 2 according to Common
Terminology Criteria for Adverse Events (CTCAE) v.4.03
10) Chronic daily treatment with oral corticosteroids
(dose of > 10 mg/day methylprednisolone equivalent). Inhaled
steroids and short courses of oral steroids for anti-emesis or as an
appetite stimulant are allowed
11) Pregnant or breastfeeding women (pregnancy needs to be excluded
by testing of beta-human chorionic gonadotropin [β-hCG])
12) Known or suspected central nervous system metastases
13) Known dihydropyrimidine dehydrogenase-deficiency
(special screening not required)
14) Known alcohol or drug abuse or any other medical or psychiatric
condition which contraindicates participation in the study
15) Documented myocardial infarction or unstable/uncontrolled
cardiac disease (ie, unstable angina, congestive heart failure
[New York Heart Association > Class II]) within 6 months of
randomization
16) Active tuberculosis or history of latent tuberculosis that has not been treated
17) Any chronic medical condition that, in the opinion of the Investigator, would make the subject unsuitable for the study or would prevent compliance with the study protocol.
18) Serious systemic fungal, bacterial, viral, or other infection that is
not controlled or requires intravenous antibiotics
19) Experimental medical treatment within 28 days prior to
randomization
20) Known hypersensitivity to any of the study drugs or excipients or
to Chinese hamster ovary cell products or to recombinant human or
humanized antibodies or known allergic reactions to products that contain platinum
21) History of long QT syndrome or whose corrected QT interval (QTc)
measured using Fridericia's formula (QTcF = QT/RR0.333) at screening
is prolonged (> 450 ms for males and > 470 ms for females)
22) Subjects with potassium, magnesium or calcium less than the lower
limit of normal (LLN); electrolyte replacement is permitted during
screening

E.5 End points

E.5.1

Primary end point(s)

Overall survival (OS) - defined as the time from date of randomization to death from any cause

E.5.1.1

Timepoint(s) of evaluation of this end point

[Time Frame: Up to 8 years]

E.5.2

Secondary end point(s)

The following secondary endpoints will be defined and analyzed in this study:
1) Progression free survival (PFS) – defined as the time from randomization to the earlier of first documentation of definitive disease progression or death from any cause
2) Objective response rate (ORR) – defined as the proportion of subjects who achieve a CR or PR as assessed by RECIST v1.1
3) Safety measurements including incidence of adverse events, clinical relevant changes in laboratory values and vital signs.

E.5.2.1

Timepoint(s) of evaluation of this end point

1.[Time Frame: Up to 8 years]
2.[Time Frame: Up to 8 years]

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

Chile

Colombia

Czech Republic

France

Germany

Hungary

Italy

Peru

Poland

Romania

Spain

Turkey

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the trial will be defined as when all subjects have completed LTFU (Long Term Follow-Up) or discontinued their participation in the study due to death, withdrawal of consent or lost to follow up.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

172

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

258

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Blind or iliterate subjects can be included with appropriate documentation

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

324

F.4.2.2

In the whole clinical trial

430

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After a patient has completed/terminated their study participation, long term care for the participant will remain the responsibility of their primary treating physicians.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-02-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-05-15

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