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

NCT00423696 | Completed Phase 2 DMC

• 4 other identifiers: CDR0000523435FRE-FNCLCC-ACCORD-13-0503EU-206662005-000070-43
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 15

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 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. It is not yet known which combination chemotherapy regimen is more effective when given together with bevacizumab in treating patients with colorectal cancer. PURPOSE: This randomized phase II trial is studying bevacizumab to compare how well it works when given together with two different combination chemotherapy regimens 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; recurrent colon cancer; recurrent rectal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 6 months

Secondary Outcomes (7)

• Percentage of objective responses

• Percentage of stable disease responses

• Duration of objective response and stable disease

• Progression-free survival

• Overall survival

Study Arms (2)

bevacizumab + FOLFIRI

EXPERIMENTAL

Biological: bevacizumab; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium

bevacizumab + XELIRI

EXPERIMENTAL

Biological: bevacizumab; Drug: capecitabine; Drug: irinotecan hydrochloride

Interventions

bevacizumab BIOLOGICAL

bevacizumab + FOLFIRI; bevacizumab + XELIRI

capecitabine DRUG

bevacizumab + XELIRI

fluorouracil DRUG

bevacizumab + FOLFIRI

irinotecan hydrochloride DRUG

bevacizumab + FOLFIRI; bevacizumab + XELIRI

leucovorin calcium DRUG

bevacizumab + FOLFIRI

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed colorectal cancer * Unresectable metastatic disease * Measurable disease * No CNS metastases PATIENT CHARACTERISTICS: * WHO performance status 0-2 * Life expectancy \> 3 months * Absolute neutrophil count \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Hemoglobin \> 9 g/dL (transfusion allowed) * INR \< 1.5 * Alkaline phosphatase \< 1.5 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN * AST and ALT \< 2.5 times ULN (5 times ULN if liver metastases are present) * Creatinine clearance \> 30 mL/min * Urine protein \< 2+ OR ≤ 1 g/L by 24-hour urine collection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No contraindications to study therapy * No gastrointestinal or duodenal ulcers * No AIDS * No serious illness, active infection, or other serious condition that would preclude study therapy * No coagulation problem * No bleeding diathesis * No sensitivity to Chinese hamster ovarian cells or other recombinant human antibodies * No severe renal insufficiency * No uncontrolled hypertension * No active or severe cardiovascular conditions, including the following: * Cerebrovascular accident * Myocardial infarction within the past 6 months * New York Heart Association class II-IV cardiac insufficiency * Severe cardiac arrhythmia (even if treated) * No primitive stenosis or symptomatic peritoneal carcinosis causing a risk of intestinal subocclusion or occlusion * No nonhealing wound or fracture * No prior thromboembolic disease * No other cancer within the past 2 years except for basal cell skin cancer or carcinoma in situ of the uterine cervix * No geographical, social, or psychological condition that would preclude study participation PRIOR CONCURRENT THERAPY: * No prior chemotherapy for metastatic disease * At least 6 months since prior adjuvant chemotherapy (fluorouracil with or without oxaliplatin) * No prior adjuvant chemotherapy comprising irinotecan hydrochloride with or without bevacizumab * At least 28 days since prior major surgery * Prior radiotherapy allowed except to target lesions * At least 10 days since prior anticoagulants * No concurrent chronic acetylsalicylic acid (at doses \> 325 mg/day) * No other concurrent investigational therapy * No other concurrent anticancer therapy

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

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (15)

C.H.U. de Brest

Brest, 29200, France

Location

Centre Regional Francois Baclesse

Caen, 14076, France

Location

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Polyclinique des Quatre Pavillons

Lormont, 33310, France

Location

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, 13273, France

Location

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie Hopital

Paris, 75248, France

Location

Polyclinique Francheville

Périgueux, 24004, France

Location

Institut Jean Godinot

Reims, 51056, France

Location

Centre Eugene Marquis

Rennes, 35062, France

Location

Centre Rene Huguenin

Saint-Cloud, 92210, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Related Publications (2)

• Malka D, Boige V, Jacques N, Vimond N, Adenis A, Boucher E, Pierga JY, Conroy T, Chauffert B, Francois E, Guichard P, Galais MP, Cvitkovic F, Ducreux M, Farace F. Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab. Ann Oncol. 2012 Apr;23(4):919-27. doi: 10.1093/annonc/mdr365. Epub 2011 Aug 8.

  PMID: 21825101 RESULT

• Antoun S, Bayar MA, Dyevre V, Lanoy E, Smolenschi C, Ducreux M. No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer. BMC Cancer. 2019 Aug 28;19(1):847. doi: 10.1186/s12885-019-6086-2.

  PMID: 31462288 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Capecitabine; Fluorouracil; Irinotecan; Leucovorin

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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Michel Ducreux, MD, PhD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: January 16, 2007
• First Posted: January 18, 2007
• Study Start: March 23, 2006
• Primary Completion: July 28, 2008
• Study Completion: August 1, 2011
• Last Updated: February 17, 2021

Record last verified: 2021-02

Locations

FR (15)