Bevacizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

NCT00797485 | Unknown Phase 3

• 3 other identifiers: CDR0000617983SICOG-0803EudraCT-2008-004890-17
• Study Type: interventional
• Target: 672
• 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. 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. PURPOSE: This phase III trial is studying how well giving induction therapy with bevacizumab together with combination chemotherapy with or without capecitabine followed by bevacizumab maintenance 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

Outcome Measures

Primary Outcomes (1)

• Time to failure of strategy

Secondary Outcomes (5)

• Response according to RECIST criteria

• Duration of response

• Progression-free survival

• Safety according to NCI CTCAE v3.0

• Quality of life as assessed by EORTC QLQ-C30 questionnaire (v 3.0) at baseline, every 3 months during induction chemotherapy, and at discontinuation of treatment

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. 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

Arm II

EXPERIMENTAL

Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

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

Interventions

bevacizumab BIOLOGICAL

Given IV

Arm I; Arm II

capecitabine DRUG

Given orally

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

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed colorectal cancer * Metastatic disease that is not amenable to surgery * At least one measurable lesion according to RECIST criteria * No untreated brain metastases or spinal cord compression PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Life expectancy ≥ 12 weeks * Hemoglobin ≥ 9.0 g/dL * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and/or 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) * PT-INR/PTT \< 1.5 times ULN * Creatinine clearance \> 50 mL/min OR serum creatinine ≤ 1.5 times ULN * Proteinuria on dipstick urinalysis \< 2+ OR 24-hour urine protein ≤ 1g * Not pregnant or nursing * Negative pregnancy test * Must be accessible for treatment and follow-up * No history of inflammatory bowel disease and/or acute or subacute bowel occlusion * No serious non-healing wound, ulcer, or bone fracture * No evidence of bleeding diathesis or coagulopathy * No uncontrolled hypertension * 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 * New York Heart Association grade II-IV congestive heart failure * Serious cardiac arrhythmia requiring medication * No known allergy to Chinese hamster ovary cell proteins or any of the components of the study medications * No other malignancy within the past 5 years except basal cell and squamous cell skin cancer or carcinoma in situ of the cervix * No significant traumatic injury within the past 28 days * No substance abuse or medical, psychological, or social conditions that may interfere with participation in the study or the evaluation of study results * Able to swallow oral medications PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 6 months since prior adjuvant treatment * No prior irinotecan and/or bevacizumab during prior adjuvant therapy * No prior cytotoxic drugs for the metastatic disease * More than 10 days since prior and no concurrent anticoagulants for therapeutic purposes * No chronic, daily treatment with high-dose aspirin (\> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration * No treatment with any investigational drug within the past 30 days * No major surgical procedure or open biopsy within the past 28 days or anticipated need for a major surgical procedure during the course of the study

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

Sponsors & Collaborators

• Southern Italy Cooperative Oncology Group: lead

Study Sites (1)

Southern Italy Cooperative Oncology Group

Naples, 80131, Italy

RECRUITING

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

• Pasquale Comella, MD

  Istituto Nazionale per lo Studio e la Cura dei Tumori

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 22, 2008
• First Posted: November 25, 2008
• Study Start: July 1, 2008
• Primary Completion: July 1, 2011
• Last Updated: August 26, 2013

Record last verified: 2009-06

Locations

IT (1)