Immediate Compared With Delayed Chemotherapy in Advanced Colorectal Cancer Without Signs or Symptoms of Disease

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which treatment regimen is more effective for colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of immediate with delayed fluorouracil plus leucovorin in treating patients with advanced colorectal cancer without signs or symptoms of disease.

Detailed Description
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OBJECTIVES: I. Compare survival and quality of life in asymptomatic patients with advanced colorectal cancer randomized to immediate fluorouracil/leucovorin (5-FU/CF) vs. 5-FU/CF delayed until onset of symptoms. OUTLINE: Randomized, unblinded study. Arm I: Single-Agent Chemotherapy with Drug Modulation. Fluorouracil, 5-FU, NSC-19893; with Leucovorin calcium, CF, NSC-3590. Arm II: Observation followed by Single-Agent Chemotherapy with Drug Modulation. Clinical observation until symptomatic; followed by 5-FU; with CF. PROJECTED ACCRUAL: 144 patients will be entered over 4 years.

Official Title
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A Phase III Study of Immediate Versus Delayed Chemotherapy for Asymptomatic Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: leucovorin calcium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed cancer of the colon or rectum that is locally advanced or metastatic Primary lesion was or is located in the large bowel as confirmed by endoscopy, radiology, or surgery Radiologic or clinical evidence of metastasis subsequent to resection does not require histologic or cytologic confirmation unless: Interval between primary surgery and development of metastasis is greater than 5 years OR Primary cancer was Dukes' A or B1 Ineligible for potentially curative therapy, e.g.: Surgical resection of a limited hepatic or pulmonary metastasis Irradiation of locally recurrent colon or rectal cancer No or minimal symptoms related to the cancer, i.e.: No persistent pain requiring regular narcotic analgesia No persistent fever greater than 38 degrees C No symptomatic bowel obstruction No persistent nausea requiring medication No weight loss of greater than 5 kg over the previous 3 months unless clearly not associated with the cancer (e.g., associated with surgery or intercurrent illness) Symptomatic relapse/metastases rendered asymptomatic by secondary surgery or radiotherapy are eligible provided the patient remains asymptomatic for at least 6 weeks following such treatment No CNS metastases No significant ascites, pleural effusion, or pericardial effusion PATIENT CHARACTERISTICS: Age: Adult under 80 (i.e., of legal age to sign own informed consent according to institutional policy) Performance status: Karnofsky 90-100% ECOG 0 Hematopoietic: Granulocytes at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than upper limit of normal Renal: Creatinine less than 2.26 mg/dL Cardiovascular: No arrhythmia Other: No infection No other medical condition that is uncontrolled or could be aggravated by the protocol therapy No prior or concurrent second cancer except: Nonmelanomatous skin cancer In situ cervical cancer No pregnant women Adequate contraception required of fertile patients Blood/body fluid analyses to determine eligibility and quality-of-life questionnaire completed within 14 days prior to randomization; imaging studies of sites of disease completed within 28 days prior to randomization PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for metastatic disease or local recurrence Prior fluorouracil-based or other adjuvant therapy allowed At least 6 months required between completion of therapy and documentation of metastasis or recurrence Endocrine therapy: Not specified Radiotherapy: Prior radiotherapy allowed Surgery: Prior surgery allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fluorouracil and folinic acid<br> | Drug: fluorouracil<br>* 425 mg/m2 IV by bolus injection daily for 5 consecutive days q 28 days<br>Drug: leucovorin calcium<br>* 20 mg/m2 IV - number of cycles is determined by patient and physician<br>|
| No Intervention: Observation<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life |  | 8 years | 
| Toxicity |  | 8 years | 
| Time to progression |  | 8 years | 
| response rate |  | 8 years | 
| response duration |  | 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III colon cancer, stage IV colon cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer