Irinotecan, Fluorouracil, Leucovorin, and Oxaliplatin as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

Phase II Trial Of Irinotecan + 5-Fluorouracil + Leucovorin + Oxaliplatin As First-Line Treatment For Metastatic Colorectal Cancer

RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy as first-line therapy in treating patients who have metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: oxaliplatin

Detailed Description

OBJECTIVES:

Primary

• Determine the tumor response rate in patients with metastatic colorectal cancer treated with irinotecan, fluorouracil, leucovorin calcium, and oxaliplatin as first-line treatment.

Secondary

• Determine the time to tumor progression, time to treatment failure, and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the quality of life of patients treated with this regimen.
• Determine whether UGT1A1 polymorphism is related to toxicity (especially leukopenia, diarrhea, or neutropenia) or response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive irinotecan IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV and fluorouracil IV over 90 minutes on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before each chemotherapy course, and at the end of treatment.

Patients are followed every 3 months until 5 years after registration.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of colorectal adenocarcinoma

  • Metastatic disease
• Not curable by surgery or amenable to radiotherapy with curative intent

• Measurable disease

  • Patients with only lesions measuring ≥ 1 cm but < 2 cm must use spiral CT scan for pre- and post-treatment tumor assessments
• No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST ≤ 5 times upper limit of normal (ULN)
• Bilirubin ≤ 0.5 mg/dL above ULN

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No unstable angina
• No symptomatic congestive heart failure
• No serious uncontrolled cardiac arrhythmia

Pulmonary

• No prior clinical diagnosis of interstitial lung disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active or uncontrolled infection
• No other concurrent serious illness
• No pre-existing paraesthesias/dysesthesias of ≥ grade 2 that would interfere with function
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated noninvasive carcinomas

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent sargramostim (GM-CSF)

Chemotherapy

• At least 6 months since prior adjuvant chemotherapy
• No prior fluorouracil for advanced colorectal cancer
• No prior adjuvant oxaliplatin
• No prior adjuvant irinotecan

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to > 25% of bone marrow

Surgery

• At least 4 weeks since prior major surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: irinotecan + oxaliplatin + leucovorin + fluorouracil; Patients receive irinotecan IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV and fluorouracil IV over 90 minutes on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before each chemotherapy course, and at the end of treatment. Patients are followed every 3 months until 5 years after registration.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tumor response rate	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	Up to 5 years
quality of life	Up to 5 years
time to treatment failure	Up to 5 years
time to progression	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Charles Erlichman, MD, Mayo Clinic

Publications and helpful links

General Publications

• McWilliams RR, Goetz MP, Morlan BW, Salim M, Rowland KM, Krook JE, Ames MM, Erlichman C. Phase II trial of oxaliplatin/irinotecan/5-fluorouracil/leucovorin for metastatic colorectal cancer. Clin Colorectal Cancer. 2007 May;6(7):516-21. doi: 10.3816/CCC.2007.n.017.

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): April 1, 2005
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: April 7, 2004
• First Submitted That Met QC Criteria: April 7, 2004
• First Posted (Estimate): April 8, 2004

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: NCCTG-N0341; NCI-2012-02581 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000357571 (Registry Identifier: PDQ (Physician Data Query))