Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma MedDRA version: 9.1 Level: LLT Classification code 10063916 Term: Metastatic gastric cancer MedDRA version: 9.1 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction
Conditions
Interventions
Product Name: AMG 386
Product Code: AMG 386
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AMG 386
Current Sponsor code: AMG 386
Concentration unit: mg/ml milligram(s)
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease Related • Histologically or cytologically confirmed adenocarcinoma of the stomach, gastroesophageal junction or distal esophagus with metastatic disease. All scans and x-rays used to document measurable or non-measurable disease must be done within 28 days prior to randomization • Measurable or non-measurable disease per modified RECIST (Response Evaluation Criteria in Solid Tumor) Guidelines Demographic • 18 years of age or older at the time the written informed consent is obtained • Subjects of child-bearing potential and sexually active must use an accepted and effective non-hormonal method of contraception (ie, double barrier method [eg, condom plus diaphragm]) from signing the informed consent through 6 months following last administration of study drug General • Able to tolerate intravenous infusions • Able to swallow oral medication • ECOG performance status of 0 or 1 (within 14 days prior to randomization) • Subject plans to begin protocol directed therapy within 7 days of randomization Laboratory Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to randomization: • Hematological function, as follows: o Absolute neutrophil count (ANC) = 1.5 x 109/L o Platelet count = 75 x 109/L and = 850 x 109/L o Hemoglobin = 9 g/dL o PTT and INR = ULN • Renal function, as follows: o Creatinine clearance = 60 mL/min - Investigators may calculate creatinine clearance by either Cockcroft-Gault formula or 24 hour urine creatinine clearance. Creatinine clearance (mL/min) = (140–age) x actual body weight (kg) (x 0.85 for females) 72 x serum creatinine (mg/dL) • Hepatic function, as follows: o Total bilirubin = 1.5 x ULN o SGOT (AST) and SGPT (ALT) = 2.5 x ULN (= 5 x ULN if liver metastases are present) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Disease Related • Prior chemotherapy for metastatic disease (1st line) • Less than 12 months have elapsed from completion of previous adjuvant or neoadjuvant chemotherapy or chemoradiotherapy • Subjects with persistant gastric outlet obstruction, complete dysphagia or feeding jejunostomy • Current or prior history of central nervous system metastases • History of bleeding diathesis or clinically significant bleeding within 14 days prior to randomization • Major surgical procedure within 28 days prior to randomization • Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days prior to first dose • Prior malignancy (other than in situ cervical cancer, or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for = 3 years prior to randomization • Clinically significant cardiovascular diseases within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication • Presence of clinically significant non-healing wound, ulcer or fracture as judged by the investigator • Ongoing or clinically significant active infection as judged by the investigator • Known hypersensitivity to bacterial proteins, or any of the drugs required in this study • Known peripheral neuropathy = Grade 1 • Known dihydropyrimidine dehydrogenase deficiency • Known hypersensitivity to 5-FU/capecitabine • Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen • Known active or chronic hepatitis Medications • Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2 including, but not limited to, AMG 386, XL880, XL820 • Treatment with immune modulators such as cyclosporine or tacrolimus within 30 days prior to randomization • Treatment with sorivudine or its chemically related analogues such as brivudine • Anticoagulants (other than aspirin) including *coumarin-type anticoagulants (other than low dose prophylaxis for central venous catheters = 1mg/day) or heparin (except for low molecular weight heparin for prophylaxis against central venous catheter thrombosis) within 7 days prior to randomization * Coumarin-type anticoagulants may be used in subjects receiving capecitabine with an increased frequency of INR and PTT monitoring. General • Any condition which in the investigator’s opinion makes the subject unsuitable for study participation • Not yet completed at least 30 days since ending other investigational device/drug trial(s), or subject is receiving other investigational treatments • Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding • Previously enrolled into this study • Inability to comply with protocol and/or not available for follow-up assessments
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To evaluate the safety and tolerability of the combination regimen of AMG 386 with CX - To estimate other measures of treatment effect (objective response rate, duration of response, overall survival, time to progression and time to response) - To evaluate the pharmacokinetics of AMG 386 when used in combination with CX - To estimate the immunogenicity as assessed by the incidence of anti-AMG 386 antibody formation - To estimate the impact of AMG 386 on cancer-related symptoms based on patient reported outcomes using the QLQ-STO22;Main Objective: To estimate the treatment effect as measured by progression free survival (PFS) of subjects receiving AMG 386 (at 2 doses) in combination with CX relative to CX/placebo;Primary end point(s): Primary: PFS: defined as time from date of randomization to date of disease progression (per the modified RECIST criteria) or death. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. Secondary: • Incidence of Adverse Events (AEs) and significant laboratory changes from baseline • Objective Response Rate (ORR): the incidence of either confirmed Complete Response (CR) or confirmed Partial Response (PR) per the modified RECIST criteria. A confirmed CR requires two assessments of CR at least 28 days apart. Two assessments at least 28 days apart of either CR or PR are required for a determination of PR. Subjects who do not meet the criteria for confirmed response by the database cutoff date are considered to be non-responders • Duration of Response (DOR): (only calculated for those subjects who respond) time from first confirmed objective response to disease progression (per the modified RECIST criteria). Subjects who do not meet the criteria for progression or who die by the database cutoff date for analysis are censored at their last evaluable disease assessment date • Overall Survival (OS): time from date of randomiza | — |
Countries
Austria, Belgium, France, Hungary, Netherlands, Spain, United Kingdom
Outcome results
None listed