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

December 2, 2011 updated by: H. Lee Moffitt Cancer Center and Research Institute

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • 5-FU
  • oxaliplatin
  • leucovorin
  • bevacizumab
  • Fluorouracil
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:
  • 5-FU
  • oxaliplatin
  • leucovorin
  • 5-Fluorouracil
  • bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: Average of 12 months
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).
Average of 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Radiographic Response
Time Frame: Average of 12 months
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).
Average of 12 months
Overall Survival
Time Frame: Average of 12 Months
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).
Average of 12 Months
Number of Participants with Adverse Events
Time Frame: Average of 12 months
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.
Average of 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Anticipated)

July 1, 2012

Study Completion (Anticipated)

July 1, 2012

Study Registration Dates

First Submitted

August 2, 2010

First Submitted That Met QC Criteria

August 3, 2010

First Posted (Estimate)

August 4, 2010

Study Record Updates

Last Update Posted (Estimate)

December 5, 2011

Last Update Submitted That Met QC Criteria

December 2, 2011

Last Verified

December 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-16145

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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