Combination Chemotherapy as First-Line Therapy in Treating Older Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

Federation Francophone de Cancerologie Digestive

Status and phase: Completed; Phase 3

Conditions: Colorectal Cancer

Treatments: Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: fluorouracil

Study type: Interventional

Funder types: Other

Identifiers

NCT00303771

CDR0000453855

EU-20546

FFCD-2001-02

AVENTIS-FFCD-2001-02

PFIZER-FFCD-2001-02

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) in different doses or combinations may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating colorectal cancer.

PURPOSE: This randomized clinical trial is studying how well fluorouracil works together with leucovorin with or without irinotecan in treating older patients with metastatic colorectal cancer .

Full description

OBJECTIVES:

Primary

• Compare the progression-free survival of elderly patients with unresectable metastatic colorectal cancer treated with 1 of 2 different chemotherapy regimens comprising fluorouracil and leucovorin calcium with vs without irinotecan hydrochloride.

Secondary

• Compare the tumor response rate and overall survival of patients treated with these regimens.
• Compare the tolerability of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter, prospective study. Patients are stratified according to participating center, gender, Karnofsky score (60-70% vs 80-90% vs 100%), associated comorbidities (Charlson Index 0 vs 1-2 vs 3+), age (75 to 79 years vs ≥ 80 years), alkaline phosphatase level (≤ 2 times normal vs > 2 times normal), and prior adjuvant chemotherapy (yes vs no). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 22 hours on days 1 and 2.
• Arm II: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1 and 2.
• Arm III: Patients receive leucovorin calcium and fluorouracil as in arm I and irinotecan hydrochloride IV over 90 minutes on day 1.
• Arm IV: Patients receive leucovorin calcium and fluorouracil as in arm II and irinotecan hydrochloride as in arm III.

In all arms, treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Patients undergo surgery within 3-10 weeks after completing chemotherapy.

Quality of life is assessed at baseline and then every 2 months thereafter.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 282 patients will be accrued for this study.

Enrollment: 282 patients

Sex: All

Ages: 75 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

  • Metastatic disease
  • Unresectable disease

• Measurable disease that is outside the field of prior irradiation

• No brain metastases

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Transaminases ≤ 5 times normal
• Bilirubin ≤ 1.5 times normal
• Alkaline phosphatase < 3 times normal (5 times normal if due to hepatic involvement)
• Creatinine clearance > 45 mL/min
• Life expectancy > 3 months
• No psychological, social, or geographical situation that would preclude study treatment
• No chronic diarrhea or enteropathy
• No coronary insufficiency or symptomatic cardiac disease
• No other malignancy unless curatively treated
• No contraindication to chemotherapy

PRIOR CONCURRENT THERAPY:

• At least 6 months since prior adjuvant chemotherapy for the primary tumor
• No prior extensive resection
• No other concurrent anticancer therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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282 participants in 4 patient groups

LV5FU2 classique

Active Comparator group

Description:

LV5FU2 classique

Treatment:

Drug: leucovorin calcium

Drug: fluorouracil

LV5FU2 classique + irinotécan

Experimental group

Description:

LV5FU2 classique + irinotécan

Treatment:

Drug: leucovorin calcium

Drug: irinotecan hydrochloride

Drug: fluorouracil

LV5FU2 simplifié

Active Comparator group

Description:

LV5FU2 simplifié

Treatment:

Drug: leucovorin calcium

Drug: fluorouracil

LV5FU2 simplifié+ irinotécan

Experimental group

Description:

LV5FU2 simplifié + irinotécan

Treatment:

Drug: leucovorin calcium

Drug: irinotecan hydrochloride

Drug: fluorouracil