A Clinical Study to evaluate the efficacy and safety of GS-5745 in combination with standard of care in patients with stomach cancer.
- Conditions
- MedDRA version: 19.0 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-001526-42-FR
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 430
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 (aPTT) = 1.5 x upper limit of normal (ULN) within
7 days prior to randomization
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 1.5 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 = 60 mL/min based on the
Cockroft-Gault formula. Subjects with a CLcr just below
60 mL/min may be eligible if a measured creatinine clearance
(based on 24 hour urine collection or other reliable method) is
= 60 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
6 months after the last dose of 5-FU 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
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) Radiotherapy within 28 days of randomization. Patients given
palliative radiotherapy to peripheral sites (eg, bone metastasis) may
enter the study before 28 days have elapsed but must have
recovered from any 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 [ß-hCG])
12) Known or suspected central nervous system metastases
13) Known dihydropyrimidine dehydrogenase-deficiency
(special screening not required)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy of GS-5745 versus placebo in combination with mFOLFOX6 as measured by overall survival (OS);<br> Secondary Objective: To compare the efficacy of GS-5745 versus placebo in combination with mFOLFOX6 as measured by progression-free survival (PFS)<br> <br> 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)<br> <br> To compare the safety of GS-5745 versus placebo in combination with mFOLFOX6<br> ;Primary end point(s): Overall survival (OS) - defined as the time from date of randomization to death from any cause;Timepoint(s) of evaluation of this end point: [Time Frame: Up to 8 years]
- Secondary Outcome Measures
Name Time Method <br> Timepoint(s) of evaluation of this end point: 1.[Time Frame: Up to 8 years]<br> 2.[Time Frame: Up to 8 years]<br> ;<br> Secondary end point(s): The following secondary endpoints will be defined and analyzed in this study:<br> 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<br> 2) Objective response rate (ORR) – defined as the proportion of subjects who achieve a CR or PR as assessed by RECIST v1.1<br> 3) Safety measurements including incidence of adverse events, clinical relevant changes in laboratory values and vital signs.<br>