Phase 1b/2 Study of AMG 655 With mFOLFOX6 and Bevacizumab for First-Line Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00625651
First received: February 14, 2008
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

This phase 1/2, multi-center, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of AMG 655 when combined with mFOLFOX6 and bevacizumab compared with mFOLFOX6 and bevacizumab alone in subjects with previously untreated metastatic colorectal cancer (CRC).

The clinical benefit of AMG 655 in combination with mFOLFOX6 and bevacizumab will be measured by progression-free survival, objective response rate, time to response, duration of response, and overall survival. This study is also designed to evaluate the safety and tolerability of AMG 655 in combination with mFOLFOX6 and bevacizumab and to evaluate anti-AMG 655 antibody formation and the pharmacokinetics of AMG 655.


Condition Intervention Phase
Metastatic Colorectal Cancer
Colon Cancer
Colorectal Cancer
Rectal Cancer
Drug: Placebo
Drug: AMG 655
Drug: Modified FOLFOX6
Drug: Bevacizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of AMG 655 in Combination With Modified FOLFOX6 and Bevacizumab for the First-Line Treatment of Subjects With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Length of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate [ Time Frame: Length of study ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Length of study ] [ Designated as safety issue: No ]
  • Time-to-response [ Time Frame: Length of study ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
  • AMG 655 pharmacokinetic parameters [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
  • The incidence of anti-AMG 655 antibody formation [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]

Enrollment: 202
Study Start Date: October 2007
Study Completion Date: September 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AMG 655 Low Dose
AMG 655 (low dose) + mFOLFOX6 + Bevacizumab
Drug: AMG 655
AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5).
Drug: Modified FOLFOX6
Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days)
Other Name: mFOLFOX6
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).
Placebo Comparator: Placebo
Placebo + mFOLFOX6 + Bevacizumab
Drug: Placebo
Inactive dummy AMG 655 (to maintain blind)
Drug: Modified FOLFOX6
Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days)
Other Name: mFOLFOX6
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).
Experimental: AMG 655 High Dose
AMG 655 (high dose) + mFOLFOX6 + Bevacizumab
Drug: AMG 655
AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5).
Drug: Modified FOLFOX6
Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days)
Other Name: mFOLFOX6
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum.
  • Subjects with measurable or unmeasurable disease
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  • Men or women at least 18 years of age
  • Adequate hematologic, renal, hepatic and coagulation function

Exclusion Criteria:

  • History or known presence of central nervous system (CNS) metastases
  • Prior chemotherapy or other systemic therapy for advanced or metastatic CRC
  • Any investigational agent or therapy for advanced or metastatic CRC
  • Clinically significant cardiac disease
  • Clinically significant peripheral neuropathy
  • Active inflammatory bowel disease
  • Recent gastrointestinal ulcer or hemorrhage
  • Recent arterial thrombotic event or pulmonary embolus
  • Recent history of clinically significant bleeding, bleeding diathesis, or coagulopathy
  • Recent major surgical procedure or not yet recovered from major surgery
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625651

  Show 61 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00625651     History of Changes
Other Study ID Numbers: 20060464
Study First Received: February 14, 2008
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Colon Cancer
Colorectal Cancer
Rectal Cancer
AMG 655
Bevacizumab
Modified FOLFOX6
mFOLFOX6
FOLFOX

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014