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

NCT00719550 | Completed Phase 1

• 1 other identifier: 20060317
• Study Type: interventional
• Target: 130
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Esophagogastric Junction Adenocarcinoma; Gastric Cancer; Esophageal Cancer

Keywords

Locally Advanced; Metastatic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

Study Arms (4)

Phase 2 Arm C

PLACEBO COMPARATOR

AMG 102 placebo plus ECX

Drug: Capecitabine; Drug: Epirubicin; Drug: Cisplatin; Drug: Placebo

Phase 1b

OTHER

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; Drug: Epirubicin; Drug: AMG 102; Drug: Cisplatin

Phase 2 Arm B

ACTIVE COMPARATOR

AMG 102 at 7.5mg/kg plus ECX

Drug: Capecitabine; Drug: Epirubicin; Drug: AMG 102; Drug: Cisplatin

Phase 2 Arm A

ACTIVE COMPARATOR

AMG 102 at 15mg/kg plus ECX

Drug: Capecitabine; Drug: Epirubicin; Drug: AMG 102; Drug: Cisplatin

Interventions

Capecitabine DRUG

Administered at 625mg/m2 BID orally every day while on study.

Also known as: Xeloda

Phase 1b; Phase 2 Arm A; Phase 2 Arm B; Phase 2 Arm C

Epirubicin DRUG

Administered day 1 of each cycle at 50mg/m2 IV.

Phase 1b; Phase 2 Arm A; Phase 2 Arm B; Phase 2 Arm C

AMG 102 DRUG

Investigation product to be given at 15mg/kg, 7.5mg/kg, or 5mg/kg depending on assignment.

Phase 1b; Phase 2 Arm A; Phase 2 Arm B

Cisplatin DRUG

Administered day 1 of each cycle at 60mg/m2 IV.

Phase 1b; Phase 2 Arm A; Phase 2 Arm B; Phase 2 Arm C

Placebo DRUG

AMG 102 placebo will be provided in similar vials as clear, colorless, sterile protein-free solution

Phase 2 Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related Publications (6)

• Doshi S, Loh E, Oliner K, Gisleskog PO, Perez Ruixo JJ, Zhang Y, Zhu M.Exposure survival modeling.Journal-001088;

  BACKGROUND

• 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.

  PMID: 24965569 BACKGROUND

• Oliner K.BM Ph2 Gastric.Journal-004521;

  BACKGROUND

• TBD.Ph2 Gastric Exposure Response.Journal-004521;

  BACKGROUND

• TBD.Ph2 Gastric PRO.Journal-004521;

  BACKGROUND

• Zhu.20060317 ER data.Journal-000728;

  BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms; Neoplasm Metastasis

Interventions

Capecitabine; Epirubicin; rilotumumab; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2008
• First Posted: July 21, 2008
• Study Start: February 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: June 1, 2013
• Last Updated: December 5, 2013

Record last verified: 2013-11