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

Colorectal Cancer Clinical Trial

Official title:

A Phase II Trial of Oral Thalidomide as an Adjuvant Agent Following Metastasectomy in Patients With Recurrent Colorectal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00019747
• Other study ID #: 990102
• Secondary ID: 99-C-0102CDR0000
• Status: Terminated
• Phase: Phase 2
• First received: July 11, 2001
• Last updated: October 6, 2015
• Start date: August 1999
• Est. completion date: December 2008

Study information

• Verified date: September 2015
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• 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).

Procedure:
• 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.

Other:
• Placebo
oral placebo once daily

Locations

Country	Name	City	State
United States	Suburban Hospital Cancer Program	Bethesda	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Center for Cancer Care at Goshen Health System	Goshen	Indiana
United States	UPMC Cancer Center at UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Progression	Time to progression was measured from the on study date until the date of progression or last follow up. Progression was assessed by the Response Evaluation Criteria for Solid Tumors (RECIST).Progressive Disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions	62 months	No