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

Study Overview
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Brief Summary
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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).

Official Title
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A Multicenter, Double-Blind, 3-Arm, Phase 1b/2 Study in Subjects With Unresectable Locally Advanced or Metastatic Gastric or Esophagogastric Junction Adenocarcinoma to Evaluate the Safety and Efficacy of First-line Treatment With Epirubicin, Cisplatin, and Capecitabine(ECX) Plus AMG 102

Conditions
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Esophagogastric Junction Adenocarcinoma, Gastric Cancer, Esophageal Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Epirubicin
* Drug: AMG 102
* Drug: Cisplatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Phase 2 Arm C<br>AMG 102 placebo plus ECX | Drug: Capecitabine<br>* Administered at 625mg/m2 BID orally every day while on study.<br>* Other names: Xeloda;Drug: Epirubicin<br>* Administered day 1 of each cycle at 50mg/m2 IV.<br>Drug: Cisplatin<br>* Administered day 1 of each cycle at 60mg/m2 IV.<br>Drug: Placebo<br>* AMG 102 placebo will be provided in similar vials as clear, colorless, sterile protein-free solution<br>|
| Other: Phase 1b<br>Phase 1b dose study with open-labe AMG 102 at 15mg/kg de-escalating to 7.5mg/kg and 5mg/kg if needed. | Drug: Capecitabine<br>* Administered at 625mg/m2 BID orally every day while on study.<br>* Other names: Xeloda;Drug: Epirubicin<br>* Administered day 1 of each cycle at 50mg/m2 IV.<br>Drug: AMG 102<br>* Investigation product to be given at 15mg/kg, 7.5mg/kg, or 5mg/kg depending on assignment.<br>Drug: Cisplatin<br>* Administered day 1 of each cycle at 60mg/m2 IV.<br>|
| Active Comparator: Phase 2 Arm B<br>AMG 102 at 7.5mg/kg plus ECX | Drug: Capecitabine<br>* Administered at 625mg/m2 BID orally every day while on study.<br>* Other names: Xeloda;Drug: Epirubicin<br>* Administered day 1 of each cycle at 50mg/m2 IV.<br>Drug: AMG 102<br>* Investigation product to be given at 15mg/kg, 7.5mg/kg, or 5mg/kg depending on assignment.<br>Drug: Cisplatin<br>* Administered day 1 of each cycle at 60mg/m2 IV.<br>|
| Active Comparator: Phase 2 Arm A<br>AMG 102 at 15mg/kg plus ECX | Drug: Capecitabine<br>* Administered at 625mg/m2 BID orally every day while on study.<br>* Other names: Xeloda;Drug: Epirubicin<br>* Administered day 1 of each cycle at 50mg/m2 IV.<br>Drug: AMG 102<br>* Investigation product to be given at 15mg/kg, 7.5mg/kg, or 5mg/kg depending on assignment.<br>Drug: Cisplatin<br>* Administered day 1 of each cycle at 60mg/m2 IV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally Advanced, Metastatic