MRI in Predicting Response in Patients Receiving Combination Chemotherapy and Bevacizumab For Advanced or Metastatic Colorectal Cancer

NCT00602329 | Terminated Phase 2 DMC FDA Drug

• 4 other identifiers: CDR0000580810UPCC-09205GENENTECH-UPCC-09205UPCC-804021
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. Diagnostic procedures, such as MRI, may help doctors predict a patient's response to treatment and help plan the best treatment. PURPOSE: This randomized phase II trial is studying how well MRI works in predicting response to combination chemotherapy given together with bevacizumab in treating patients with advanced or metastatic colorectal cancer.

Conditions

Colorectal Cancer

Keywords

recurrent colon cancer; recurrent rectal cancer; stage III colon cancer; stage III rectal cancer; stage IV colon cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (1)

• Analysis of tumor blood flow, assessed by DCE-MRI as percentage change in Ktrans, after 2 courses of FOLFOX and bevacizumab or FOLFOX alone compared to baseline value

  2 cycles for all subjects

Secondary Outcomes (3)

• Analysis of tumor markers of angiogenesis and apoptosis, and the effect of treatment

  2 cycles for all subjects

• Correlation of tumor blood flow with time to progression

  2 cycles

• Correlation of markers of apoptosis in tumor cells with response to therapy, time to progression, and overall survival

  2 cycles for all subjects

Study Arms (3)

Arm I

EXPERIMENTAL

Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours (FOLFOX) beginning on day 1. Patients also receive bevacizumab at 5 mg/kg IV over 90 minutes on day 1. Treatment repeats every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin

Arm II

EXPERIMENTAL

Patients receive FOLFOX as in arm I and bevacizumab at 10 mg/kg IV over 90 minutes on day 1. Treatment repeats every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin

FOLFOX alone (control)

ACTIVE COMPARATOR

Patients receive FOLFOX as in arm I.

Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin

Interventions

bevacizumab BIOLOGICAL

Given IV

Arm I; Arm II

fluorouracil DRUG

Given IV

Arm I; Arm II; FOLFOX alone (control)

leucovorin calcium DRUG

Given IV

Arm I; Arm II; FOLFOX alone (control)

oxaliplatin DRUG

Given IV

Arm I; Arm II; FOLFOX alone (control)

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed advanced or metastatic adenocarcinoma of the colon or rectum * Patients receiving bevacizumab must have tumor tissue available for immunohistochemical analysis * Formalin-fixed, paraffin-embedded tissue from previous biopsy or surgical resection is sufficient * Measurable disease, defined by RECIST as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques (i.e., CT or MRI) * CEA elevation alone is insufficient for study entry * No known brain metastases PATIENT CHARACTERISTICS: Criteria for all patients * ECOG performance status 0-1 * Life expectancy \> 3 months * Granulocytes ≥ 1,500/mL * Platelet Count ≥ 100,000/mL * Creatinine ≤ 1.5 times upper limit of normal (ULN) * Bilirubin ≤ 1.5 times ULN * AST ≤ 5 times ULN * Urine protein:creatinine ratio ≤ 1.0 at screening * Patients with other prior malignancies are eligible, provided they have been treated with curative intent and have no evidence of recurrence * Not pregnant or nursing * Negative pregnancy test * No contraindications to MRI, including any of the following: * Hypersensitivity to gadolinium * Metallic device, including pacemaker, non-MRI compatible aneurysm clip, other non-MRI-compatible mechanical and/or electrical device, or metallic fragments * Severe claustrophobia Additional criteria for patients receiving bevacizumab: * No significant traumatic injury within the past 28 days * No serious nonhealing wounds, ulcers, or bone fractures * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No myocardial infarction, unstable angina, or cerebrovascular accident within the past 6 months * No clinically significant peripheral vascular disease * No New York Heart Association class II-IV congestive heart failure * Patients with pre-existing hypertension should be on a stable antihypertensive regimen with blood pressure ≤ 150/100 mm Hg at study entry PRIOR CONCURRENT THERAPY: Criteria for all patients * Prior adjuvant treatment including oxaliplatin allowed * No prior bevacizumab * At least 14 days since prior radiotherapy and recovered * More than 6 months since prior chemotherapy * No other concurrent investigational agents Additional criteria for patients receiving bevacizumab: * At least 28 days since prior major surgical procedure or open biopsy * At least 7 days since prior minor surgical procedure (e.g., fine-needle aspirations or core biopsies) * No anticipation of need for a major surgical procedure during study treatment * Concurrent oral or parenteral anticoagulation therapy allowed provided dose is stable

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Fluorouracil; Leucovorin; Oxaliplatin

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Peter O'Dwyer, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2008
• First Posted: January 28, 2008
• Study Start: February 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: October 1, 2009
• Last Updated: April 28, 2020

Record last verified: 2020-04

Locations

US (1)