RATIONALE: Thalidomide may stop the growth of colorectal cancer by stopping blood flow to the tumor. Giving thalidomide after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying surgery and thalidomide to see how well they work compared to surgery alone in treating patients with recurrent or metastatic colorectal cancer.

Condition	Treatment or Intervention	Phase
stage IV colon cancer Stage IV rectal cancer recurrent colon cancer recurrent rectal cancer	Drug: thalidomide  Procedure: adjuvant therapy  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the disease-free survival probability in patients with previously resected recurrent or metastatic colorectal carcinoma treated with adjuvant thalidomide vs placebo.
• Compare the time to recurrence in patients treated with these regimens.
• Determine whether serum/plasma levels of vascular endothelial growth factor and basic fibroblast growth factor preresection and postresection correlate with tumor recurrence and determine if these levels, as well as CEA measurements, aid in predicting time to recurrence in these patients.
• Determine the pharmacokinetics and toxicity of long-term thalidomide therapy in these patients.
• Determine whether patients receiving thalidomide develop measurable antiangiogenic activity.
• Measure the presence of circulating tumor cells preresection and postresection and determine if this type of analysis can be used to predict recurrence in this patient population.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to site of most recent lesion resection that rendered no evidence of disease (lung vs liver with no more than 3 lesions vs liver with more than 3 lesions vs lung and liver vs all other sites[including sites that were both resected and ablated]). Patients without evidence of residual disease are randomized to one of two treatment arms.

• Arm I: Patients receive oral thalidomide once daily.
• Arm II: Patients receive an oral placebo once daily. Treatment continues in both arms for 2 years in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for up to 3 years.

PROJECTED ACCRUAL: A total of 94 patients (47 per treatment arm) will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of recurrent or metastatic colorectal carcinoma previously resected within 12 weeks of study entry
• Surgical resection combined with radiofrequency ablation allowed

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 8.0 g/dL
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• PTT/PT no greater than 120% of control (except in therapeutically anticoagulated nonrelated medical conditions [e.g., atrial fibrillation])
• Total bilirubin no greater than 1.5 mg/dL (direct bilirubin no greater than 1.0 mg/dL for patients with Gilbert's syndrome)
• AST/ALT less than 2.5 times normal
• No history of hepatic cirrhosis
• No concurrent hepatic dysfunction

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No severe congestive heart failure or active ischemic heart disease
• No active clots within 1 year before diagnosis OR must be receiving concurrent treatment with anticoagulant (e.g., low molecular weight heparin or equivalent agent)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 1 highly effective method of contraception AND 1 additional effective method of contraception for least 4 weeks before, during, and for at least 4 weeks after study participation
• No history of severe hypothyroidism
• No history of seizures
• No significant history of other medical problems that would preclude surgery
• No peripheral neuropathy greater than grade 1, except localized neuropathy due to a mechanical cause or trauma

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 4 weeks since prior biologic therapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• See Cardiovascular
• No concurrent sedating drugs that cannot be reduced to a minimal level
• No concurrent sedating recreational drugs or alcohol
• No concurrent antiseizure medications

Indiana
      Center for Cancer Care at Goshen Health System, Goshen,  Indiana,  46526,  United States; Recruiting
Maryland
      Suburban Hospital Cancer Program, Bethesda,  Maryland,  20817,  United States; Recruiting
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
Ohio
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0558,  United States; Recruiting
Pennsylvania
      University of Pittsburgh Medical Center, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting

Study chairs or principal investigators

Steven K. Libutti, MD,  Study Chair,  NCI - Surgery Branch   

Study ID Numbers:  CDR0000067098; NCI-99-C-0102; PCI-020901; NCT00019747
Record last reviewed:  October 2004
Last Updated:  April 4, 2005
Record first received:  July 11, 2001
ClinicalTrials.gov Identifier:  NCT00019747
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08