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

Federation Francophone de Cancerologie Digestive

Status and phase: Completed; Phase 2

Conditions: Colorectal Cancer

Treatments: Biological: bevacizumab; Drug: leucovorin calcium; Drug: fluorouracil; Drug: irinotecan hydrochloride; Biological: filgrastim

Study type: Interventional

Funder types: Other

Identifiers

NCT00541125

FFCD-0604

EU-20757

EUDRACT-2007-001772-37

CDR0000564089

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

20 participants in 1 patient group

FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire

Other group

Description:

FOLFIRI-bévacizumab avec G-CSF en prophylaxie primaire

Treatment:

Biological: bevacizumab

Drug: irinotecan hydrochloride

Biological: filgrastim

Drug: fluorouracil

Drug: leucovorin calcium