AMG 102 Plus ECX for Unresectable Locally Advanced or Metastatic Gastric or Esophagogastric Junction Cancer

• Conditions: Advanced MET-Positive Gastric, Lower Esophageal or Gastroesophageal Junction Adenocarcinoma; MedDRA version: 18.0Level: LLTClassification code 10066354Term: Adenocarcinoma of the gastroesophageal junctionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10017761Term: Gastric cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: LLTClassification code 10017766Term: Gastric cancer stage IV NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10017765Term: Gastric cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-004923-11-PL
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-02-12
• Last Update Posted: 14 March 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

Inclusion Criteria

Disease Related
• Pathologically confirmed unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma; adenocarcinomas of the distal esophagus within 5 cm of the GEJ are eligible
• ECOG performance status (0 or 1)
• Tumor MET-positive by IHC (= 25% tumor membrane staining as defined by an investigational use only MET IHC assay) by protocol-specified centralized testing
• Formalin fixed paraffin-embedded (FFPE) tumor tissue submission required
• Evaluable (measurable or non-measurable) disease by RECIST 1.1 criteria

Demographic
• Men or women = 18 years of age

Ethical
• Before any study-specific procedure, the appropriate written informed consent must be obtained (Section 11.1)

Laboratory
• Adequate organ function as evidenced by the following laboratory studies within 28 days prior to randomization:
- Hemoglobin = 9 g/dL
- Absolute neutrophil count = 1.5 x 109/L
- Platelet count = 100 x 109/L
- Creatinine clearance = 60mL/minute (calculated or measured)
- Aspartate aminotransferase (AST) and alanine amino transferase (ALT) = 2.5 x ULN or AST and ALT = 5.0 x ULN if liver metastases are present
- Total bilirubin = 1.5x ULN

General
• Able to tolerate infusions and take oral medications

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 395
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 205

Exclusion Criteria

Exclusion Criteria

Disease Related
• HER2-overexpressing locally advanced or metastatic gastric or GEJ adenocarcinoma. Subjects whose tumor HER2 expression status is not known must submit tumor samples for HER2 testing
• Previous systemic therapy (including chemotherapy, biologic, immunotherapy, or investigational therapy) for locally advanced or metastatic gastric or GEJ or lower esophageal (within 5 cm of GEJ) adenocarcinoma Less than 6 months have elapsed from completion of prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy to randomization
• Previous treatment with anthracyclines exceeds total cumulative dose of epirubicin of 400 mg/m2 (or equivalent thereof, if a different anthracycline has been administered in the past)
• Subjects with ongoing toxicities from palliative radiotherapy, or who have undergone radiotherapy to the only site of known disease, or received palliative radiation = 14 days prior to randomization. Subjects who received palliative
radiotherapy are otherwise eligible.
• Squamous cell histology
• Subjects with resectable disease or suitable for definitive chemoradiation
• Plans for surgical resection or definitive chemoradiation based on response to protocol therapy
• Subjects who have persistent gastric outlet obstruction, complete dysphagia or are dependent upon jejunostomy for feeding
• Known central nervous system metastases
• Clinically significant upper gastro-intestinal bleeding < 30 days prior to randomization

Other Medical Conditions
• Left ventricular ejection fraction (LVEF) < 50% as determined by either multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
• Documented myocardial infarction or unstable/uncontrolled cardiac disease (eg, unstable angina, severe arrhythmias, congestive heart failure [New York Heart Association (NYHA) > Class II]) within 6 months before randomization (Appendix E)
• Presence of peripheral edema > grade 1
• Arterial thrombosis or vascular ischemic events, such as transient ischemic attack, cerebral infarction, within six months prior to randomization
• Subjects with venous thromboembolic events (including deep vein thrombosis or pulmonary emboli) within 6 months prior to randomization
• Serious or non-healing wound
• Known positive HepBsAg (indicative of acute or chronic Hepatitis B) or detectable Hepatitis C virus (indicative of active Hepatitis C), known positive test for HIV
• Known peripheral neuropathy > grade 1
• Known dihydropyrimidine dehydrogenase deficiency (DPD)
• History of any medical condition including cardiovascular disease or chronic obstructive pulmonary disease (COPD), that in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study resultsMajor surgical procedure = 30 days before randomization or not yet recovered from prior major surgery. Major surgery is defined within this protocol 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)
• Minor surgery (eg, catheter or gastrostomy tube placement) =14 days before randomization or not yet recovered from prior minor surgery. Placement of central venous access device, fine needle aspiration, thoracentesis, endoscopic biliary stent or paracentesis = 1 day before randomization is acceptable

Study & Design

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