A PHASE II Study of GM-CSF As Pre- And Post-Operative Adjuvant Therapy For Stage II And III Colon Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
A PHASE II Study of GM-CSF As Pre- And Post-Operative Adjuvant Therapy For Stage II And III Colon Cancer
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Proportion of patients with a change in tumor-associated macrophage VEGF expression
Safety Issue:
No
Principal Investigator
Alok A. Khorana, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
James P. Wilmot Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000448633
NCT ID:
NCT00262808
Start Date:
March 2004
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage II colon cancer
- stage III colon cancer
- adenocarcinoma of the colon
- Colonic Neoplasms
- Colorectal Neoplasms
Name | Location |
|---|---|
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
