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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00262808
• Other study ID #: CDR0000448633
• Secondary ID: URCC-U1203URCC-R
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2005
• Last updated: October 14, 2013
• Start date: March 2004
• Est. completion date: September 2006

Study information

• Verified date: October 2013
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Biological:
• sargramostim

Drug:
• fluorouracil

• leucovorin calcium

• oxaliplatin

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Locations

Country	Name	City	State
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with a change in tumor-associated macrophage VEGF expression			No
Secondary	Disease-free and overall survival			No