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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


Phase 2
18 Years
74 Years
Not Enrolling
Both
Colorectal Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Supportive Care

Outcome Measure:

Rate of neutropenia grade 4 or fever

Principal Investigator

Thierry Lecomte, MD

Investigator Role:

Study Chair

Investigator Affiliation:

CHRU de Tours - Hopital Trousseau

Authority:

Unspecified

Study ID:

CDR0000564089

NCT ID:

NCT00541125

Start Date:

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • recurrent colon cancer
  • stage IV colon cancer
  • recurrent rectal cancer
  • stage IV rectal cancer
  • adenocarcinoma of the colon
  • adenocarcinoma of the rectum
  • Colorectal Neoplasms
  • Neutropenia

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