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

March 27, 2020 updated by: Federation Francophone de Cancerologie Digestive

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional 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
Drug: fluorouracil
Drug: leucovorin calcium
Drug: irinotecan hydrochloride
Biological: filgrastim
Biological: bevacizumab

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federation Francophone de Cancerologie Digestive

Investigators

  • Study Chair: Thierry Lecomte, MD, CHRU de Tours - Hôpital Trousseau

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

October 5, 2007

First Submitted That Met QC Criteria

October 5, 2007

First Posted (Estimate)

October 8, 2007

Study Record Updates

Last Update Posted (Actual)

March 30, 2020

Last Update Submitted That Met QC Criteria

March 27, 2020

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000564089
  • FFCD-0604
  • EU-20757
  • EUDRACT-2007-001772-37

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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