MedDRA version: 20.0 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Code: GS-5745
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: GS-5745
Current Sponsor code: GS-5745
Other descri
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
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 = 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). 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 for 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
Exclusion criteria
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 [ß-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 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of GS-5745 versus placebo in combination with mFOLFOX6 as measured by overall survival (OS); Secondary Objective: 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 ;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
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1.[Time Frame: Up to 8 years] 2.[Time Frame: Up to 8 years] ; 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. | — |
Countries
Australia, Belgium, Chile, Colombia, Czech Republic, France, Germany, Hungary, Italy, Peru, Poland, Romania, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed