Clinical trial NCT00080951: Irinotecan, Fluorouracil, Leucovorin, and Oxaliplatin as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer
Official title: Phase II Trial Of Irinotecan + 5-Fluorouracil + Leucovorin + Oxaliplatin As First-Line Treatment For Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-08
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: tumor response rate
timeFrame: Up to 5 years
Secondary outcomes:
measure: time to progression
timeFrame: Up to 5 years
measure: overall survival
timeFrame: Up to 5 years
measure: time to treatment failure
timeFrame: Up to 5 years
measure: quality of life
timeFrame: Up to 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Charles Erlichman, MD
role: STUDY_CHAIR
References:
citation: 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.