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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier:
NCT00541125
First received: October 5, 2007
Last updated: March 3, 2014
Last verified: October 2007
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Biological: filgrastim
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Federation Francophone de Cancerologie Digestive:

Primary Outcome Measures:
  • Rate of neutropenia grade 4 or fever [ Time Frame: 2013 ] [ Designated as safety issue: Yes ]
  • Toxicities by NCI-CTC v. 2.0 [ Time Frame: 2013 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective response at 6 months by RECIST [ Time Frame: 2013 ] [ Designated as safety issue: No ]
  • Tolerance (except neutropenia) by NCI-CTC v. 2.0 [ Time Frame: 2013 ] [ Designated as safety issue: Yes ]
  • Progression-free survival [ Time Frame: 2013 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2013 ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: 2013 ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: November 2007
Study Completion Date: December 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire
FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire
Biological: bevacizumab Biological: filgrastim Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium

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.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00541125

Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
Study Chair: Thierry Lecomte, MD CHRU de Tours - Hopital Trousseau
  More Information

Additional Information:
No publications provided

Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT00541125     History of Changes
Other Study ID Numbers: CDR0000564089, FFCD-0604, EU-20757, EUDRACT-2007-001772-37
Study First Received: October 5, 2007
Last Updated: March 3, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Federation Francophone de Cancerologie Digestive:
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Neutropenia
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Fluorouracil
Irinotecan
Bevacizumab
Camptothecin
Lenograstim
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 24, 2014