FOLFOX/Bevacizumab +/- MK-0646 in Metastatic Colorectal Cancer

This study has been withdrawn prior to enrollment.
(treatment deemed ineffective so accrual was closed)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01175291
First received: August 2, 2010
Last updated: December 2, 2011
Last verified: December 2011
  Purpose

The purpose is to study the efficacy (effectiveness) of a new drug, MK-0646, in metastatic colorectal cancer. MK-0646 is an investigational or experimental anti-cancer agent that has not yet been approved by the U.S. Food and Drug Administration (FDA) for use in metastatic colorectal cancer or any other disease.

This study will assess whether adding MK-0646 to an FDA-approved standard of care chemotherapy improves participants' duration of progression-free survival. MK-0646 is believed to inhibit the receptor of a protein called IGF-1 (Insulin-like Growth Factor) which is thought to contribute to cancer development and growth. However, there is no guarantee that MK-0646 will slow cancer development and growth.

Other purposes of this study include:

  • looking at the safety and tolerability of MK-0646
  • comparing MK-0646 + standard of care chemotherapy with placebo + standard of care chemotherapy (placebo is a substance that looks like an active drug but has no active ingredient) The standard of care chemotherapy in this study is called FOLFOX 7. FOLFOX 7 includes the drugs oxaliplatin with leucovorin, 5-Fluorouracil (5-FU), and bevacizumab.

Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: MK-0646
Drug: Placebo
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: Randomized, Double Blind Phase II Study of FOLFOX/Bevacizumab Combined With MK-0646 Versus FOLFOX/Bevacizumab Combined With Placebo in First-Line Treatment of Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Average of 12 months ] [ Designated as safety issue: No ]
    To determine whether the administration of MK-0646 with FOLFOX and bevacizumab (experimental arm) improves progression-free survival (PFS) versus FOLFOX and bevacizumab combined with placebo (control arm).


Secondary Outcome Measures:
  • Objective Radiographic Response [ Time Frame: Average of 12 months ] [ Designated as safety issue: No ]
    To determine whether the objective radiographic response (ORR) is higher in patients treated with FOLFOX and bevacizumab combined with MK-0646 (experimental arm) versus FOLFOX and bevacizumab combined with placebo (control arm).

  • Overall Survival [ Time Frame: Average of 12 Months ] [ Designated as safety issue: No ]
    To determine whether overall survival (OS) is higher in patients treated with FOLFOX and bevacizumab combined with MK-0646 (experimental arm) versus FOLFOX and bevacizumab combined with placebo (control arm).

  • Number of Participants with Adverse Events [ Time Frame: Average of 12 months ] [ Designated as safety issue: Yes ]
    To determine the safety and tolerability of MK-0646 combined with FOLFOX and bevacizumab. Safety and tolerability will be assessed according to the NIH/NCI CTC Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.


Enrollment: 0
Study Start Date: September 2010
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A - FOLFOX 7 + MK-0646 Drug: MK-0646
ARM A will receive FOLFOX 7 (Oxaliplatin with leucovorin + 5-Fluorouracil [5-FU] + Bevacizumab) + MK-0646 (Investigational).
Other Names:
  • oxaliplatin
  • leucovorin
  • 5-FU
  • Fluorouracil
  • bevacizumab
Placebo Comparator: Arm B - FOLFOX 7 + Placebo Drug: Placebo
ARM B will receive FOLFOX 7 (Oxaliplatin with leucovorin + 5-Fluorouracil [5-FU] + Bevacizumab) + placebo: standard of care chemotherapy plus placebo.
Other Names:
  • oxaliplatin
  • leucovorin
  • 5-FU
  • 5-Fluorouracil
  • bevacizumab

Detailed Description:

Participants randomized to ARM A will receive modified FOLFOX 7 every other week + MK-0646 every week:

5-FU 400 mg/m2 by intravenous infusion over 2-5 minutes Leucovorin 400 mg/m2 by intravenous infusion over 2 hours Oxaliplatin 85 mg/m2 by intravenous infusion over 2 hours (with leucovorin) Bevacizumab 5 mg/kg by intravenous infusion over 30 minutes (+/- 15 minutes) following infusions may be given over 10 minutes (+/- 10 minutes) if the first infusion is tolerated well.

5-FU 2400 mg/m2 by continuous intravenous infusion over 46 hours (may be delivered via automated outpatient pump) Antiemetics (drugs that prevent nausea and vomiting): 5-HT3 receptor antagonist (e.g. ondansetron) and dexamethasone are recommended prior to chemotherapy.

MK-0646 10 mg/kg by intravenous infusion over 60 minutes every week (participants larger than 100 kg [220 pounds] will receive their infusions over 120 minutes).

Participants randomized to ARM B will receive modified FOLFOX 7 every other week + placebo every week:

5-FU 400 mg/m2 by intravenous infusion over 2-5 minutes Leucovorin 400 mg/m2 by intravenous infusion over 2 hours Oxaliplatin 85 mg/m2 by intravenous infusion over 2 hours (with leucovorin) Bevacizumab 5 mg/kg by intravenous infusion over 30 minutes (+/- 15 minutes); following infusions may be given over 10 minutes (+/- 10 minutes) if the first infusion is tolerated well.

5-FU 2400 mg/m2 by continuous intravenous infusion over 46 hours (may be delivered via automated outpatient pump) Antiemetics: 5-HT3 receptor antagonist (e.g. ondansetron) and dexamethasone are recommended prior to chemotherapy Placebo by intravenous infusion over 60 minutes every week (participants larger than 100 kg [220 pounds] will receive their infusions over 120 minutes).

  Eligibility

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

Inclusion Criteria:

  • Metastatic colorectal adenocarcinoma.
  • Measurable disease by RECIST criteria.
  • Adequate hepatic function: total bilirubin ≤2.0 x upper limits of normal (ULN); Aspartate Amino Transferase (AST)/Alanine Amino Transferase (ALT) ≤3.0X upper limits of normal (or ≤5X upper limits of normal if attributable to liver metastases).
  • Adequate renal function: serum creatinine ≤2.0 mg/dl.
  • Adequate bone marrow function: absolute neutrophil count ≥1,500/mm3; platelets ≥ 100,000/mm3.
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels ≤1.5 upper limit of normal (unless patients receiving coumadin anticoagulation in which case a stable international normalized ratio (INR) of 2-3 is required).
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Life expectancy ≥ 12 weeks.
  • Negative pregnancy test.
  • Ability to sign informed consent.

Exclusion Criteria:

  • Prior systemic chemotherapy for metastatic colorectal cancer
  • Prior oxaliplatin in the adjuvant setting within 12 months
  • Uncontrolled central nervous system metastases or carcinomatous meningitis.
  • Myocardial infarction in the past 6 months.
  • Major surgery within 8 weeks prior to enrollment.
  • Uncontrolled serious medical or psychiatric illness.
  • Inadequately controlled hypertension (defined as systolic blood pressure >160mmHg, or diastolic blood pressure > 100mmHg).
  • Pregnant or lactating women. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of study.
  • Prior experimental therapy targeting the IGF-1 pathway
  • Concurrent malignancy (with the exception of squamous or basal cell skin carcinoma)
  • Planned surgical metastasectomy
  • Patient has known hypersensitivity to components of treatment, their analogs, or drugs of similar chemical or biologic composition
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01175291     History of Changes
Other Study ID Numbers: MCC-16145
Study First Received: August 2, 2010
Last Updated: December 2, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
colon
rectum
colorectal
metastatic
adenocarcinoma

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Bevacizumab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on April 14, 2014