G-CSF in Preventing Neutropenia During First-Line Treatment With Chemotherapy and Bevacizumab in Patients With Metastatic Colorectal Cancer

NCT ID: NCT00541125

Last Updated: 2020-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2013-12-31

Brief Summary

RATIONALE: G-CSF may prevent or control neutropenia caused by first-line therapy in patients with metastatic colorectal cancer.

PURPOSE: This phase II trial is studying how well G-CSF works in preventing neutropenia during first-line treatment with chemotherapy and bevacizumab in patients with metastatic colorectal cancer.

Detailed Description

OBJECTIVES:

Primary

• Determine if primary prophylaxis comprising filgrastim (G-CSF) makes it possible to obtain neutropenia lower than grade 4 or a 30% decrease in fever in patients with metastatic colorectal cancer receiving first-line FOLFIRI and bevacizumab and who are homozygous for allele UGT1A1*28 (genotype 7/7), a promoter of the gene coding for enzyme UGT1A1.

Secondary

• Evaluate the objective response rate at 6 months of treatment with FOLFIRI and bevacizumab according to RECIST criteria.
• Evaluate the toxicity (excluding neutropenia) of FOLFIRI and bevacizumab according to NCI-CTC v. 2.0.
• Determine progression-free and overall survival.
• Determine the time to treatment failure.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Patients also receive filgrastim (G-CSF) subcutaneously on days 5-11. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 2-3 months for up to 5 years.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire

FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire

Group Type: OTHER

bevacizumab

Intervention Type: BIOLOGICAL

filgrastim

Intervention Type: BIOLOGICAL

fluorouracil

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

Interventions

bevacizumab

Intervention Type: BIOLOGICAL

filgrastim

Intervention Type: BIOLOGICAL

fluorouracil

Intervention Type: DRUG

irinotecan hydrochloride

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed adenocarcinoma of the colon or rectum

• Metastatic disease
• Not surgically curable
• Homozygous for allele UGT1A1*28, the promoter of the gene coding for UGT1A1 (genotype 7/7)
• Measurable and/or evaluable disease

• WHO performance status 0-2
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Creatinine > 1.5 mg/dL
• Total bilirubin ≤ 1.5 times normal
• Alkaline phosphatase ≤ 2.5 times normal (5 times normal if liver involvement)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients of must use effective contraception

• At least 2 weeks since prior radiotherapy

Exclusion Criteria

• Original tumor not removed
• CNS metastases
• Secondary localized cerebral tumors

PATIENT CHARACTERISTICS:

• Progressive gastroduodenal ulcer, prior hemorrhagic ulcer, or perforation in the past 6 months
• Enteropathy or chronic diarrhea
• Chronic inflammatory intestinal disease
• Intestinal obstruction
• Active cardiac disease including any of the following:

• Uncontrolled hypertension
• Myocardial infarction in the past 12 months
• Serious angina
• NYHA class II-IV congestive heart failure
• Severe arrhythmia (even if treated)
• Peripheral vascular disease ≥ grade 2
• Unhealed wound, ulcer, or severe bone fracture
• Bleeding disorder or coagulopathy
• Severe uncontrolled infection or medical condition
• Proteinuria > 500 mg/24 hours
• Other malignancy within the past 5 years except basal cell skin cancer or curatively treated carcinoma in situ of the cervix
• Known dihydropyrimidine dehydrogenase deficiency
• Severe traumatic injury within the past 4 weeks

PRIOR CONCURRENT THERAPY:

• Prior chemotherapy for metastatic disease except adjuvant chemotherapy completed > 6 months ago
• Prior irinotecan hydrochloride or bevacizumab
• Major surgery or biopsy within the past 4 weeks
• Major surgery planned
• Puncture in the past week
• Chronic aspirin (> 325 mg/day) or NSAIDs
• Concurrent antifungal azoles (e.g., ketoconazole, fluconazole, itraconazole)
• Concurrent phenytoin (as in yellow fever vaccine)
• Concurrent Hypericum perforatum (St. John's wort)
• Oral or parenteral coagulant in the past 10 days and during study therapy

• Warfarin allowed provided INR < 1.5

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thierry Lecomte, MD

Role: STUDY_CHAIR

CHRU de Tours - Hopital Trousseau

Other Identifiers

FFCD-0604

Identifier Type: -

Identifier Source: secondary_id

EU-20757

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2007-001772-37

Identifier Type: -

Identifier Source: secondary_id

CDR0000564089

Identifier Type: -

Identifier Source: org_study_id