Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

NCT00467142 | Completed Phase 2 Results

• 5 other identifiers: CDR0000540522IB-2006-31IB-OMEGAINCA-RECF0387EUDRACT-2006-003901-22
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: 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 colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with combination chemotherapy works as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants in Objective Response (Partial or Complete Responses)

  Objective response defined as complete or partial responses according to RECIST v1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.).Radiologic assessment was carried out every four cycles (8 weeks) with centralized external secondary review.

  6 months

Secondary Outcomes (1)

• Median Duration of Response

  24 months

Study Arms (1)

Folfiri and Bevacizumab

EXPERIMENTAL

* Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. * FOLFIRI (simplified LV5FU2 + irinotecan): * Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. * LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser * Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated.

Biological: bevacizumab; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Genetic: polymorphism analysis

Interventions

bevacizumab BIOLOGICAL

Folfiri and Bevacizumab

fluorouracil DRUG

Folfiri and Bevacizumab

irinotecan hydrochloride DRUG

Folfiri and Bevacizumab

leucovorin calcium DRUG

Folfiri and Bevacizumab

polymorphism analysis GENETIC

Folfiri and Bevacizumab

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the colon or rectum * No other histological types * Metastatic, unresectable disease * No bone metastases only * Unidimensionally measurable metastatic disease * No CNS metastases PATIENT CHARACTERISTICS: * WHO performance status (PS) 0-2 OR Karnofsky PS 70-100% * Life expectancy ≥ 12 weeks * ANC \> 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 10 g/dL * Bilirubin ≤ 1.25 times normal (1.5 times normal in presence of hepatic metastases) * AST and ALT \< 3 times normal (5 times normal in presence of hepatic metastases) * Creatinine \< 1.25 times normal * No proteinuria * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other cancer in the past 5 years except for carcinoma in situ of the uterine cervix or basal cell skin cancer * No hypersensitivity to fluorouracil * No hypersensitivity to leucovorin calcium, bevacizumab, or their excipients * No hypersensitivity to Chinese hamster ovarian cell products or other recombinant humanized or nonhumanized monoclonal antibodies * No allergy to irinotecan hydrochloride * No prior reaction to attenuated vaccines (fever, jaundice) * No poor nutritional status * No Biermer anemia or other anemia due to vitamin B12 deficiency * No uncontrolled symptomatic occlusion or subocclusion * No medullary hypoplasia or severe insufficiency * No prior chronic intestinal disease * No Gilbert's syndrome * No intra-abdominal inflammatory reaction (e.g., gastroduodenal ulcer, diverticulitis, or colitis) * No chronic intestinal inflammatory disease * No thromboembolic arterial condition in the past 6 months, including any of the following: * Cardiovascular accident * Transient ischemic attack * Myocardial infarction * No infection or serious noncancerous disease * No condition that is unstable or would increase risk to the patient, including any of the following: * Unstable angina * Poorly controlled hypertension * Severe cardiac insufficiency * Serious arrhythmia * Bleeding diathesis * Pulmonary disease at risk of decompensation * No familial, geographical, social, or psychological condition that would preclude study participation * No prisoners or patients without guardians PRIOR CONCURRENT THERAPY: * At least 8 weeks since prior surgery * At least 6 months since prior adjuvant chemotherapy * At least 1 month since prior palliative chemotherapy * No prior abdominal or pelvic radiotherapy * At least 30 days since prior participation in another investigational study * No prior bevacizumab * No extensive intestinal resection (e.g., partial colectomy or extensive thin resection) * No concurrent warfarin, Hypericum perforatum (St. John's wort), or prophylactic phenytoin

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

Sponsors & Collaborators

• Institut Bergonié: lead

Study Sites (1)

Institut Bergonie

Bordeaux, 33076, France

Location

Related Publications (1)

• Becouarn Y, Cany L, Pulido M, Beyssac R, Texereau P, Le Morvan V, Bechade D, Brunet R, Aitouferoukh S, Lalet C, Mathoulin-Pelissier S, Fonck M, Robert J. FOLFIRI(R) and bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms. BMC Res Notes. 2014 Apr 23;7:260. doi: 10.1186/1756-0500-7-260.

  PMID: 24758527 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Fluorouracil; Irinotecan; Leucovorin; Amplified Fragment Length Polymorphism Analysis

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; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; DNA Fingerprinting; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Results Point of Contact

• Title: Pr Yves Becouran
• Organization: Institut Bergonié

y.becouarn@bordeaux.unicancer.fr

Study Officials

• Yves Becouarn, MD

  Institut Bergonié

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2007
• First Posted: April 27, 2007
• Study Start: January 23, 2007
• Primary Completion: May 1, 2010
• Study Completion: December 1, 2011
• Last Updated: November 1, 2022
• Results First Posted: April 20, 2022

Record last verified: 2022-10

Locations

FR (1)