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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II, Multicenter Study Evaluating G-CSF as Primary Prophylaxis for Neutropenia Associated With First-line Chemotherapy Regimen FOLFIRI and Bevacizumab in Patients With Metastatic Colorectal Cancer Who Are Homozygous for UGT1A1*28 Polymorphism, the Promoter of the Gene Encoding for the Enzyme UGT1A1

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Biological: filgrastim
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: 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 Exclusion criteria: Original tumor not removed CNS metastases Secondary localized cerebral tumors PATIENT CHARACTERISTICS: Inclusion criteria: 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 Exclusion criteria: 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: Inclusion criteria: At least 2 weeks since prior radiotherapy Exclusion criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire<br>FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire | Biological: bevacizumab<br> <br> Biological: filgrastim<br> <br> Drug: fluorouracil<br> <br> Drug: irinotecan hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of neutropenia grade 4 or fever |  | 2013 | 
| Toxicities by NCI-CTC v. 2.0 |  | 2013 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response at 6 months by RECIST |  | 2013 | 
| Tolerance (except neutropenia) by NCI-CTC v. 2.0 |  | 2013 | 
| Progression-free survival |  | 2013 | 
| Overall survival |  | 2013 | 
| Time to treatment failure |  | 2013 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum