A Randomized, Double Blind, Multi-Center, Phase 2 Study to Estimate the Efficacy and Evaluate the Safety and Tolerability of Cisplatin & Capecitabine (CX) in Combination with AMG 386 or Placebo in Subjects with Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma

• Conditions: Metastatic Gastric, Gastroesophageal Junction, or Distal Esophageal Adenocarcinoma; MedDRA version: 9.1Level: LLTClassification code 10063916Term: Metastatic gastric cancer; MedDRA version: 9.1Level: LLTClassification code 10066354Term: Adenocarcinoma of the gastroesophageal junction

• Registration Number: EUCTR2007-003573-50-AT
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-02-20
• Last Update Posted: 18 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 165

Inclusion Criteria

Disease Related
• Histologically or cytologically confirmed adenocarcinoma of the stomach,
gastroesophageal junction or distal esophagus with metastatic disease.
• Subject with prior gastrectomy (total or partial) may be allowed to participate
in the study as long as they can take oral medications and meet all other
inclusion/exclusion criteria. Subjects may not take crushed or dissolved
capecitabine via a feeding/gastrostomy tube.
• Subjects who received palliative radiotherapy for the metastatic esophageal or
gastric cancer prior to study entry may be allowed to participate in the study
as long as all toxicities from radiotherapy have resolved and the radiotherapy
was not to the only site of known metastatic disease.
• Measurable or non-measurable disease per modified RECIST (Response Evaluation
Criteria in Solid Tumor) Guidelines (please refer to Appendix G). All scans and
x-rays used to document measurable or non-measurable disease must be
done within 28 days prior to randomization
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 consent to the 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:
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- Platelet count = 75 x 109/L and = 850 x 109/L
- Hemoglobin = 9 g/dL
• Coagulation function, as follows:
- PTT or aPTT = 1.5 x ULN per institutional laboratory normal range
- INR = 1.5
• Renal function, as follows:
- Urinary protein quantitative value of = 30 mg/dl in urinalysis or = 1+ on dipstick,
unless quantitative protein is < 1000 mg in a 24 hour urine sample
- Creatinine clearance = 50 mL/min
Investigators may calculate creatinine clearance (CrCl) by either Cockcroft-Gault
formula or 24 hour urine creatinine clearance.
(140-age) x actual body weight (kg)
CrCl (mL/min) = (x 0.85 for females)
72 x serum creatinine (mg/dL)
Or
(140-age) x actual body weight (kg)
CrCl (mL/min) = (x 0.85 for females)
0.8136 x serum creatinine (umol/L)
• Hepatic function, as follows:
- Total bilirubin = 1.5 x ULN
- 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

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
• Radiotherapy = 14 days prior to randomization. Subjects must have recovered
from all radiotherapy-related toxicities
• Current or prior history of central nervous system metastases
• History of arterial or deep venous thromboembolism within 12 months prior to
randomization
• History of clinically significant bleeding within 6 months prior to randomization
• Major surgical procedure within 28 days prior to randomization
• Minor surgical procedure, placement of central venous access device (PICC or
peripherally inserted central catheter lines) or fine needle aspiration within 3 days
prior to randomization
• Subjects with a history of prior malignancy, except:
- Malignancy treated with curative intent and with no known active disease
present for = 3 years prior to enrollment (or randomization) and felt to be at
low risk for recurrence by treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna
without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
• 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, percutaneous
transluminal coronary angioplasty/stent
• Non-healing wound, ulcer (including gastrointestinal) or fracture
• 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 AMG 386, or other molecules that inhibits
angiopoietin, or TIE-2 receptors including, but not limited to, XL-820, XL-184, or
CVX-060/PF-4856884
• 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
• Concurrent or prior (within 7 days prior to randomization) anticoagulation
therapy, excluding aspirin and anti-platelet agents. The concurrent use of low
molecular weight heparin or heparanoids or low dose warfarin (ie, = 1 mg daily)
for prophylaxis against thrombosis is acceptable while on study
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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified