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

Phase 1

Completed

• Conditions: Gastric Cancer; Esophageal Cancer; Esophagogastric Junction Adenocarcinoma
• Interventions: Drug: Capecitabine; Drug: Epirubicin; Drug: Cisplatin; Drug: AMG 102; Drug: Placebo

• Registration Number: NCT00719550
• Lead Sponsor: Amgen

Brief Summary

Study Phase: 1b/2 Indication: Previously untreated subjects with unresectable locally advanced or metastatic gastric or esophagogastric junction adenocarcinoma.

Primary Objective(s):

Part 1: To identify safe dose levels of AMG 102, up to 15 mg/kg Q3W, to combine with ECX.

Part 2 (phase 2-double-blind): To estimate with pre-specified precision the effect of the addition of AMG 102 to ECX on progression free survival (PFS).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-07-17
• Study First Submitted QC: 2008-07-18
• Study First Posted: 2008-07-21
• Study Start: 2009-02
• Primary Completion: 2010-11
• Disposition First Submitted: 2013-04-15
• Disposition First Submitted QC: 2013-04-15
• Disposition First Posted: 2013-04-23
• Study Completion: 2013-06
• Status Verified: 2013-11
• Last Update Submitted: 2013-11-13
• Last Update Posted: 2013-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• Pathologically confirmed unresectable locally advanced or metastatic gastric or esophagogastric junction (EGJ) adenocarcinoma; tumors of the distal esophagus within 5 cm of the EGJ are eligible
• ECOG performance status 0 or 1
• Male or female ≥ 18 years of age

Exclusion Criteria

• Previous systemic therapy (chemotherapy or biologic therapy) for locally advanced or metastatic gastric or esophagogastric adenocarcinoma
• Less than 6 months have elapsed from completion of prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy.
• Subjects with resectable disease or suitable for definitive chemoradiation
• Subjects with persistent gastric outlet obstruction, complete dysphagia or feeding jejunostomy
• Tumors of squamous cell histology
• Known central nervous system metastases
• Clinically significant upper gastro-intestinal bleeding ≤ 30 days prior to enrollment or randomization
• Serious or non-healing wound

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 Arm C	Capecitabine	AMG 102 placebo plus ECX
Phase 2 Arm C	Epirubicin	AMG 102 placebo plus ECX
Phase 2 Arm C	Placebo	AMG 102 placebo plus ECX
Phase 2 Arm B	Capecitabine	AMG 102 at 7.5mg/kg plus ECX
Phase 2 Arm C	Cisplatin	AMG 102 placebo plus ECX
Phase 1b	Capecitabine	Phase 1b dose study with open-labe AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed.
Phase 1b	Cisplatin	Phase 1b dose study with open-labe AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed.
Phase 1b	Epirubicin	Phase 1b dose study with open-labe AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed.
Phase 2 Arm B	Epirubicin	AMG 102 at 7.5mg/kg plus ECX
Phase 2 Arm A	Capecitabine	AMG 102 at 15mg/kg plus ECX
Phase 2 Arm B	Cisplatin	AMG 102 at 7.5mg/kg plus ECX
Phase 2 Arm A	Epirubicin	AMG 102 at 15mg/kg plus ECX
Phase 2 Arm A	AMG 102	AMG 102 at 15mg/kg plus ECX
Phase 2 Arm A	Cisplatin	AMG 102 at 15mg/kg plus ECX
Phase 1b	AMG 102	Phase 1b dose study with open-labe AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed.
Phase 2 Arm B	AMG 102	AMG 102 at 7.5mg/kg plus ECX

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS), as measured by RECIST per local review	Subjects coming off study will be contacted by telephone or at routine clinic visits approximately every 3 months until 36 months from date the last subject is randomized into the study.

Secondary Outcome Measures

Name	Time	Method
Overall survival, objective response rate, disease control rate, time to response (for responders only), and duration of response (for responders only).	Subjects coming off study will be contacted by telephone or at routine clinic visits approximately every 3 months until 36 months from date the last subject is randomized into the study.
Incidence of adverse events, significant laboratory value changes form baseline and anti-AMG 102 antibody formation.	Subjects coming off study will be contacted by telephone or at routine clinic visits approximately every 3 months until 36 months from date the last subject is randomized into the study.
Cmax and Cmin for AMG 102; Cmax and AUC for epirubicin and cisplatin with or without AMG 102	Subjects coming off study will be contacted by telephone or at routine clinic visits approximately every 3 months until 36 months from date the last subject is randomized into the study.