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

Phase 1

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-FR

Lead Sponsor: Amgen Inc.

Brief Summary: Not available

Detailed Description: Not available

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.
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

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials