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

Sponsored by:	James P. Wilmot Cancer Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00262808

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Drug: sargramostim Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Sargramostim Granulocyte-macrophage colony-stimulating factor Fluorouracil Oxaliplatin Calcium gluconate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A PHASE II Study of GM-CSF As Pre- And Post-Operative Adjuvant Therapy For Stage II And III Colon Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Proportion of patients with a change in tumor-associated macrophage VEGF expression [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease-free and overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	March 2004

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262808

Locations

United States, New York
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710

Sponsors and Collaborators

James P. Wilmot Cancer Center

Investigators

Principal Investigator:

Alok A. Khorana, MD

James P. Wilmot Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000448633, URCC-U1203, URCC-RSRB-09956, BRLX-001-0837, DUMC-7135-05-5R0
Study First Received:	December 6, 2005
Last Updated:	May 23, 2008
ClinicalTrials.gov Identifier:	NCT00262808
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage II colon cancer
stage III colon cancer
adenocarcinoma of the colon

Study placed in the following topic categories:

Digestive System Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Leucovorin
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms
Calcium, Dietary

Oxaliplatin
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Colonic Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on January 16, 2009