GM-CSF and Combination Chemotherapy in Treating Patients Who Are Undergoing Surgery for Stage II or Stage III Colon Cancer

Study Overview
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Brief Summary
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RATIONALE: Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy or kill tumor cells. Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, 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) may kill more tumor cells. Giving combination chemotherapy after surgery may kill any remaining tumor cells. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. PURPOSE: This phase II trial is studying how well GM-CSF and combination chemotherapy work in treating patients who are undergoing surgery for stage II or stage III colon cancer.

Detailed Description
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OBJECTIVES: Primary Determine the safety of neoadjuvant and adjuvant sargramostim (GM-CSF) and adjuvant chemotherapy in patients with resectable stage II or III colon cancer. Determine the efficacy, in terms of enhanced tumor-associated macrophage response, of this regimen in these patients. Secondary Determine overall survival and time to progression in patients treated with this regimen. OUTLINE: Neoadjuvant therapy and surgery: Patients receive sargramostim (GM-CSF) subcutaneously (SC) once daily beginning between days -16 and -12 and continuing until day -1. Patients undergo surgical resection on day 0. Patients with stage I or IV disease are removed from the study. All other patients proceed to adjuvant chemotherapy or observation. Adjuvant chemotherapy or observation: Patients with high-risk stage II or any stage III disease are assigned to group 1 or 2. Patients with low-risk stage II disease are assigned to group 3. Group 1 (adjuvant therapy for high-risk stage II disease): Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV on days 1, 8, 15, 22, 29 and 36. Patients also receive GM-CSF SC once daily on days 50-54. Treatment repeats every 56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Group 2 (adjuvant therapy for stage III disease): Patients receive adjuvant chemotherapy and GM-CSF as in group 1. Alternatively, patients may receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. These patients also receive GM-CSF SC once daily on days 10-14 of every fourth course. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Group 3 (low-risk stage II disease): Patients undergo observation only every 3 months. After completion of study treatment, patients are followed periodically for survival. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Official Title
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A PHASE II Study of GM-CSF As Pre- And Post-operative Adjuvant Therapy For Stage II And III Colon Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: sargramostim
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon Stage II or III disease No carcinoma in situ No perforated or obstructed tumors No dual primary lesions by colonoscopy or barium enema Resectable disease Distal and proximal bowel end must be > 5 cm from tumor Tumor must not extend below peritoneal reflection No distant intra-abdominal metastases (even if resected) No rectal cancer No tumors that require opening of the pelvic peritoneum to define the extent of disease PATIENT CHARACTERISTICS: Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 2.0 mg/dL Renal Creatinine ≤ 2.0 mg/dL Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No uncontrolled cardiac arrhythmia Immunologic No ongoing or active infection No allergy to yeast or yeast-based products No allergy to sargramostim (GM-CSF) No allergy to fluorouracil No allergy to leucovorin calcium Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of Crohn's disease No history of ulcerative colitis No other malignancy within the past 3 years except superficial squamous cell or basal cell skin cancer or carcinoma in situ of the cervix No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness PRIOR CONCURRENT THERAPY: Chemotherapy No prior chemotherapy, including fluorouracil, for colon cancer No other concurrent chemotherapy Radiotherapy No prior radiotherapy for colon cancer No concurrent radiotherapy Other No other prior therapy for colon cancer No concurrent immunosuppressant therapy No other concurrent investigational agents No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: sargramostim|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with a change in tumor-associated macrophage VEGF expression |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free and overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II colon cancer, stage III colon cancer, adenocarcinoma of the colon