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

Primary Purpose

Metastatic Colorectal Cancer

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

MK-0646

Placebo

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring colon, rectum, colorectal, metastatic, adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm A - FOLFOX 7 + MK-0646

Arm B - FOLFOX 7 + Placebo

Arm Description

Outcomes

Primary Outcome Measures

Progression Free Survival

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

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

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

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.

Full Information

NCT ID

NCT01175291

First Posted

August 2, 2010

Last Updated

December 2, 2011

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01175291

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2011

Overall Recruitment Status

Withdrawn

Why Stopped

treatment deemed ineffective so accrual was closed

Study Start Date

September 2010 (undefined)

Primary Completion Date

July 2012 (Anticipated)

Study Completion Date

July 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer

Keywords

colon, rectum, colorectal, metastatic, adenocarcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A - FOLFOX 7 + MK-0646

Arm Type

Active Comparator

Arm Title

Arm B - FOLFOX 7 + Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

MK-0646

Other Intervention Name(s)

oxaliplatin, leucovorin, 5-FU, Fluorouracil, bevacizumab

Intervention Description

ARM A will receive FOLFOX 7 (Oxaliplatin with leucovorin + 5-Fluorouracil [5-FU] + Bevacizumab) + MK-0646 (Investigational).

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

oxaliplatin, leucovorin, 5-FU, 5-Fluorouracil, bevacizumab

Intervention Description

ARM B will receive FOLFOX 7 (Oxaliplatin with leucovorin + 5-Fluorouracil [5-FU] + Bevacizumab) + placebo: standard of care chemotherapy plus placebo.

Primary Outcome Measure Information:

Title

Progression Free Survival

Description

Time Frame

Average of 12 months

Secondary Outcome Measure Information:

Title

Objective Radiographic Response

Description

Time Frame

Average of 12 months

Title

Overall Survival

Description

Time Frame

Average of 12 Months

Title

Number of Participants with Adverse Events

Description

Time Frame

Average of 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

12. IPD Sharing Statement

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

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