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

NCT01175291 | Withdrawn Phase 2 DMC

• 1 other identifier: MCC-16145
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Colorectal Cancer

Keywords

colon; rectum; colorectal; metastatic; adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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).

  Average of 12 months

Secondary Outcomes (3)

• Objective Radiographic Response

  Average of 12 months

• Overall Survival

  Average of 12 Months

• Number of Participants with Adverse Events

  Average of 12 months

Study Arms (2)

Arm A - FOLFOX 7 + MK-0646

ACTIVE COMPARATOR

Drug: MK-0646

Arm B - FOLFOX 7 + Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

MK-0646 DRUG

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

Also known as: oxaliplatin, leucovorin, 5-FU, Fluorouracil, bevacizumab

Arm A - FOLFOX 7 + MK-0646

Placebo DRUG

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

Also known as: oxaliplatin, leucovorin, 5-FU, 5-Fluorouracil, bevacizumab

Arm B - FOLFOX 7 + Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Adenocarcinoma

Interventions

dalotuzumab; Oxaliplatin; Leucovorin; Fluorouracil; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2010
• First Posted: August 4, 2010
• Study Start: September 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: December 5, 2011

Record last verified: 2011-12