Surgery With or Without Thalidomide in Treating Patients With Recurrent or Metastatic Colorectal Cancer

NCT ID: NCT00019747

Last Updated: 2015-10-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-08-31
• Study Completion Date: 2008-12-31

Brief Summary

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.

Detailed Description

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 carcinoembryonic antigen (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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm 1 - Thalidomide once daily

Patients receive oral thalidomide 100 mg at bedtime once daily for 4 weeks, then progresses to 200 mg at bedtime for 4 weeks, then progresses to 300 mg at bedtime (maintenance dose).

Group Type: EXPERIMENTAL

thalidomide

Intervention Type: DRUG

oral thalidomide 100 mg at bedtime once daily for 4 weeks, then progresses to 200 mg at bedtime for 4 weeks, then progresses to 300 mg at bedtime (maintenance dose).

adjuvant therapy

Intervention Type: PROCEDURE

Initial dose: 100 mg by mouth (po) every bedtime ( Q hs) for four weeks, then progress to 200 mg po Q hs for four weeks, then progress to maintenance dose: 300 mg po Q hs.

Arm 2 - Placebo once daily

Patients receive oral placebo once daily.

Group Type: PLACEBO_COMPARATOR

adjuvant therapy

Intervention Type: PROCEDURE

Initial dose: 100 mg by mouth (po) every bedtime ( Q hs) for four weeks, then progress to 200 mg po Q hs for four weeks, then progress to maintenance dose: 300 mg po Q hs.

Placebo

Intervention Type: OTHER

oral placebo once daily

Interventions

thalidomide

oral thalidomide 100 mg at bedtime once daily for 4 weeks, then progresses to 200 mg at bedtime for 4 weeks, then progresses to 300 mg at bedtime (maintenance dose).

Intervention Type: DRUG

adjuvant therapy

Initial dose: 100 mg by mouth (po) every bedtime ( Q hs) for four weeks, then progress to 200 mg po Q hs for four weeks, then progress to maintenance dose: 300 mg po Q hs.

Intervention Type: PROCEDURE

Placebo

oral placebo once daily

Intervention Type: OTHER

Other Intervention Names

Thalomid

Eligibility Criteria

Inclusion 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:

• Partial thromboplastin time (PTT)/prothrombin time (PT) no greater than 120% of control (except in therapeutically anticoagulated nonrelated medical conditions [e.g., atrial fibrillation])
• Total bilirubin no greater than 2.0 mg/dL (direct bilirubin no greater than 1.0 mg/dL for patients with Gilbert's syndrome)
• Aspartate aminotransferase (AST)/alanine aminotransferase (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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Responsible Party

Steven Rosenberg, M.D.

Dr. Steven Rosenberg

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven K. Libutti, MD

Role: STUDY_CHAIR

NCI - Surgery Branch

Locations

Center for Cancer Care at Goshen Health System

Goshen, Indiana, United States

Suburban Hospital Cancer Program

Bethesda, Maryland, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

UPMC Cancer Center at UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

99-C-0102

Identifier Type: -

Identifier Source: secondary_id

CDR0000067098

Identifier Type: -

Identifier Source: secondary_id

990102

Identifier Type: -

Identifier Source: org_study_id