G-CSF in Preventing Neutropenia During First-Line Treatment With Chemotherapy and Bevacizumab in Patients With Metastatic Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
bevacizumab
filgrastim
fluorouracil
irinotecan hydrochloride
leucovorin calcium
Sponsored by
About this trial
This is an interventional supportive care trial for Colorectal Cancer focused on measuring recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire
Arm Description
FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire
Outcomes
Primary Outcome Measures
Rate of neutropenia grade 4 or fever
Toxicities by NCI-CTC v. 2.0
Secondary Outcome Measures
Objective response at 6 months by RECIST
Tolerance (except neutropenia) by NCI-CTC v. 2.0
Progression-free survival
Overall survival
Time to treatment failure
Full Information
NCT ID
NCT00541125
First Posted
October 5, 2007
Last Updated
March 27, 2020
Sponsor
Federation Francophone de Cancerologie Digestive
1. Study Identification
Unique Protocol Identification Number
NCT00541125
Brief Title
G-CSF in Preventing Neutropenia During First-Line Treatment With Chemotherapy and Bevacizumab in Patients With Metastatic Colorectal Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Federation Francophone de Cancerologie Digestive
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire
Arm Type
Other
Arm Description
FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Primary Outcome Measure Information:
Title
Rate of neutropenia grade 4 or fever
Time Frame
2013
Title
Toxicities by NCI-CTC v. 2.0
Time Frame
2013
Secondary Outcome Measure Information:
Title
Objective response at 6 months by RECIST
Time Frame
2013
Title
Tolerance (except neutropenia) by NCI-CTC v. 2.0
Time Frame
2013
Title
Progression-free survival
Time Frame
2013
Title
Overall survival
Time Frame
2013
Title
Time to treatment failure
Time Frame
2013
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry Lecomte, MD
Organizational Affiliation
CHRU de Tours - Hopital Trousseau
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
G-CSF in Preventing Neutropenia During First-Line Treatment With Chemotherapy and Bevacizumab in Patients With Metastatic Colorectal Cancer
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