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Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing: A Randomized Trial to Assess the Role of Irinotecan and Oxaliplatin in Advanced Colorectal Cancer


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Colorectal Cancer

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Trial Information

Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing: A Randomized Trial to Assess the Role of Irinotecan and Oxaliplatin in Advanced Colorectal Cancer


OBJECTIVES:

- Compare the efficacy of combination chemotherapy comprising fluorouracil (5-FU) with
leucovorin calcium (CF) and either irinotecan (CPT-11) or oxaliplatin vs standard
sequential single-agent therapy comprising 5-FU with CF followed by CPT-11 in patients
with unresectable metastatic colorectal cancer.

- Determine whether combination chemotherapy is best used as first-line therapy or
reserved for second-line therapy after progression on first-line single-agent therapy
in these patients.

- Compare the efficacy and toxicity of an irinotecan-containing regimen vs an
oxaliplatin-containing regimen in these patients.

- Compare the overall survival, progression-free survival, and quality of life of
patients treated with these regimens.

- Compare the safety and toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to one
of five treatment arms.

- Arm I (standard therapy): Patients receive first-line chemotherapy comprising
leucovorin calcium IV over 2 hours on day 1 followed by fluorouracil IV continuously
over 46 hours on days 1-2 every 14 days. Patients with progressive disease then receive
second-line therapy comprising irinotecan IV over 90 minutes on day 1 every 21 days.

- Arm II: Patients receive first-line chemotherapy as in arm I. Patients with progressive
disease then receive second-line therapy comprising irinotecan IV over 30 minutes and
leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46
hours on days 1-2 every 14 days.

- Arm III: Patients receive first-line chemotherapy comprising irinotecan, leucovorin
calcium, and fluorouracil as in second-line therapy of arm II.

- Arm IV: Patients receive first-line chemotherapy as in arm I. Patients with progressive
disease then receive second-line therapy comprising leucovorin calcium IV and
oxaliplatin IV over 2 hours on day 1 followed by fluorouracil IV continuously over 46
hours on days 1-2 every 14 days.

- Arm V: Patients receive first-line chemotherapy comprising leucovorin calcium,
oxaliplatin, and fluorouracil as in second-line therapy of arm IV.

Treatment continues in all arms in the absence of disease progression or unacceptable
toxicity.

Quality of life is assessed at baseline, at weeks 6 and 12, and then every 12 weeks
thereafter.

PROJECTED ACCRUAL: A total of 2,100 patients (700 in arm I and 350 each in arms II-V) will
be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed metastatic adenocarcinoma of the colon or rectum

- Unresectable disease

- Measurable or evaluable disease

- No partial or complete bowel obstruction

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- WHO 0-2

Life expectancy:

- Not specified

Hematopoietic:

- WBC greater than 4,000/mm^3

- Platelet count greater than 150,000/mm^3

Hepatic:

- Bilirubin less than 1.25 times upper limit of normal (ULN)

- Alkaline phosphatase less than 5 times ULN

- AST or ALT less than 3 times ULN

- No Gilbert's syndrome or other congenital abnormality of biliary transport (e.g.,
Crigler-Najjar syndrome or Dubin-Johnson syndrome)

Renal:

- Creatinine clearance greater than 50 mL/min OR

- Glomerular filtration rate normal

Other:

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other uncontrolled medical illness

- No other prior or concurrent malignancy that would preclude study entry

- No chronic diarrhea or inflammatory bowel disease

- No grade 2 or greater pre-existing neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- At least 6 months since prior adjuvant chemotherapy

- Prior adjuvant fluorouracil allowed

- No prior chemotherapy for metastatic disease

- No prior oxaliplatin or irinotecan

Endocrine therapy:

- Not specified

Radiotherapy:

- Not specified

Surgery:

- No prior transplantation surgery requiring immunosuppressive therapy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Matthew T. Seymour, MA, MD, FRCP

Investigator Role:

Study Chair

Investigator Affiliation:

Medical Research Council

Authority:

United States: Federal Government

Study ID:

CDR0000068372

NCT ID:

NCT00008060

Start Date:

May 2000

Completion Date:

Related Keywords:

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

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