Second-Line Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer Who Have Received First-Line Chemotherapy and Bevacizumab

NCT00720512 | Terminated Phase 3

• 4 other identifiers: CDR0000598567GONO-BEBYP-ASL607LIOM03GONO-AIFA - FARM5C4FB4EUDRACT:2007-002886-11
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 21

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan, oxaliplatin, 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. 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. It is not yet known whether combination chemotherapy is more effective with or without bevacizumab in treating metastatic colorectal cancer. PURPOSE: This randomized phase III trial is studying second-line combination chemotherapy to see how well it works compared with or without bevacizumab in treating patients with metastatic colorectal cancer who have received first-line chemotherapy and bevacizumab.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  last progression of the last patient

Secondary Outcomes (3)

• Overall survival

  the end of the stady

• Response rate

  last visit of the last patient

• Safety

  the end of the study

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Drug: oxaliplatin

Arm II

EXPERIMENTAL

Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

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

Interventions

bevacizumab BIOLOGICAL

Given IV

Arm II

fluorouracil DRUG

Given IV

Arm I; Arm II

irinotecan hydrochloride DRUG

Given IV

Arm I; Arm II

leucovorin calcium DRUG

Given IV

Arm I; Arm II

oxaliplatin DRUG

Given IV

Arm I; Arm II

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 adenocarcinoma * Metastatic or unresectable disease * Progressive disease based on the following criteria: * Progression during or after first-line chemotherapy for metastatic disease, including any of the following: * Fluoropyrimidine-based monotherapy with bevacizumab * Fluoropyrimidine and irinotecan hydrochloride-based doublet with bevacizumab * Fluoropyrimidine and oxaliplatin-based doublet with bevacizumab * Progression after more than 3 months from the last administration of first-line chemotherapy for metastatic disease with a fluoropyrimidine, irinotecan hydrochloride, and oxaliplatin triplet (FOLFOXIRI) with bevacizumab to which the patient had previously responded * Measurable disease, as assessed by RECIST criteria * No prior or concurrent CNS metastasis PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy \> 3 months * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL * INR ≤ 1.5 times upper limit of normal (ULN) * aPTT ≤ 1.5 ULN * Serum bilirubin ≤ 1.5 times ULN * AST and ALT ≤ 2.5 times ULN (\< 5 times ULN if liver metastases present) * Alkaline phosphatase ≤ 2.5 times ULN (\< 5 times ULN if liver metastases present) * Serum creatinine ≤ 1.5 times ULN * Proteinuria \< 2+ OR protein ≤ 1g by 24-hour urine * Not pregnant or nursing * Fertile patients must use effective contraception * No bowel obstruction or subobstruction * No history of inflammatory enteropathy * No prior extensive intestinal resection (i.e., \> hemicolectomy or extensive small intestine resection with chronic diarrhea) * No symptomatic peripheral neuropathy \> grade 2 * No active uncontrolled infection * No active disseminated intravascular coagulation * No prior or concurrent malignancy, except for curatively treated basal cell and squamous cell carcinoma of the skin, or in situ carcinoma of the cervix * No clinically significant cardiovascular disease, including any of the following: * Cerebrovascular accident within the past 6 months * Myocardial infarction within the past 6 months * Unstable angina * NYHA class II-IV chronic heart failure * Uncontrolled arrhythmia * No uncontrolled hypertension * No thromboembolic or hemorrhagic events within the past 6 months * No evidence of bleeding diathesis or coagulopathy * No serious, non healing wound/ulcer or serious bone fracture * No significant traumatic injury within the past 28 days PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 6 weeks since prior radiotherapy * At least 4 weeks since prior surgery * No prior first-line chemotherapy for metastatic disease without bevacizumab * No prior cetuximab or other investigational agents * More than 28 days since prior open biopsy * More than 28 days since prior and no concurrent major surgical procedure * No concurrent therapeutic anticoagulation, antiplatelet agents, or NSAID with anti-platelet activity * Acetylsalicylic acid ≤ 325 mg/day allowed

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

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (21)

Universita Politecnica Delle Marche

Ancona, 60100, Italy

Location

Azienda Usl 8 Arezzo

Arezzo, 52100, Italy

Location

Ospedale degli Infermi - ASL 12

Biella, 13900, Italy

Location

A. Perrino Hospital

Brindisi, 72100, Italy

Location

Azienda Ospedaliera S. Elia

Caltanissetta, 93100, Italy

Location

Ospedale Santa Croce

Cuneo, 12100, Italy

Location

Ospedale San Giuseppe

Empoli, 50053, Italy

Location

Ospedale E. Profili

Fabriano, 60044, Italy

Location

Ospedale Civile S. Croce

Fano, 61032, Italy

Location

Azienda Ospedaliera di Firenze

Florence, 50011, Italy

Location

Azienda Ospedaliero Careggi

Florence, 50139, Italy

Location

Istituto Nazionale per la Ricerca sul Cancro

Genoa, 16132, Italy

Location

Ospendale S. Andrea EST

La Spezia, 19100, Italy

Location

Azienda Ospedaliera Vito Fazzi

Lecce, 73100, Italy

Location

Azienda USL12 Versilia

Lido di Camaiore, 55043, Italy

Location

Ospedale Campo Di Marte Lucca

Lucca, 55100, Italy

Location

Azienda Ospedaliera Maggiore Della Carita

Novara, 28100, Italy

Location

Azienda Ospedaliera Pisana

Pisa, 56126, Italy

Location

Arcispedale S. Maria Nuova

Reggio Emilia, 42100, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

Dipartimento Oncologico

Siena, 53100, Italy

Location

Related Publications (1)

• Masi G, Salvatore L, Boni L, Loupakis F, Cremolini C, Fornaro L, Schirripa M, Cupini S, Barbara C, Safina V, Granetto C, Fea E, Antonuzzo L, Boni C, Allegrini G, Chiara S, Amoroso D, Bonetti A, Falcone A; BEBYP Study Investigators. Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial. Ann Oncol. 2015 Apr;26(4):724-730. doi: 10.1093/annonc/mdv012. Epub 2015 Jan 18.

  PMID: 25600568 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Fluorouracil; Irinotecan; 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; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Alfredo Falcone, MD

  Presidio Ospedaliero di Livorno

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2008
• First Posted: July 22, 2008
• Study Start: June 1, 2008
• Primary Completion: February 1, 2013
• Study Completion: March 1, 2014
• Last Updated: March 11, 2015

Record last verified: 2015-03

Locations

IT (21)