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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00541125
• Other study ID #: CDR0000564089
• Secondary ID: FFCD-0604EU-2075
• Status: Completed
• Phase: Phase 2
• Start date: November 2007
• Est. completion date: December 2013

Study information

• Verified date: May 2016
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Neutropenia

Intervention

Biological:
• bevacizumab

• filgrastim

Drug:
• fluorouracil

• irinotecan hydrochloride

• leucovorin calcium

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of neutropenia grade 4 or fever		2013
Primary	Toxicities by NCI-CTC v. 2.0		2013
Secondary	Objective response at 6 months by RECIST		2013
Secondary	Tolerance (except neutropenia) by NCI-CTC v. 2.0		2013
Secondary	Progression-free survival		2013
Secondary	Overall survival		2013
Secondary	Time to treatment failure		2013