Clinical trial NCT00719550: AMG 102 Plus ECX for Unresectable Locally Advanced or Metastatic Gastric or Esophagogastric Junction Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Esophagogastric Junction Adenocarcinoma
Gastric Cancer
Esophageal Cancer
Keywords: Locally Advanced
Metastatic
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2008-07-21
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival (PFS), as measured by RECIST per local review
timeFrame: 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 outcomes:
measure: Overall survival, objective response rate, disease control rate, time to response (for responders only), and duration of response (for responders only).
timeFrame: 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.
measure: Incidence of adverse events, significant laboratory value changes form baseline and anti-AMG 102 antibody formation.
timeFrame: 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.
measure: Cmax and Cmin for AMG 102; Cmax and AUC for epirubicin and cisplatin with or without AMG 102
timeFrame: 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.
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Doshi S, Loh E, Oliner K, Gisleskog PO, Perez Ruixo JJ, Zhang Y, Zhu M.Exposure survival modeling.Journal-001088;
citation: Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, Nirni S, Lakshmaiah K, Thomas A, Jiang Y, Zhu M, Tang R, Anderson A, Dubey S, Oliner KS, Loh E. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014 Aug;15(9):1007-18. doi: 10.1016/S1470-2045(14)70023-3. Epub 2014 Jun 22.
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