Surgery With or Without Thalidomide in Treating Patients With Recurrent or Metastatic Colorectal Cancer
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.
Procedure: adjuvant therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Oral Thalidomide as an Adjuvant Agent Following Metastasectomy in Patients With Recurrent Colorectal Cancer|
- Time to Progression [ Time Frame: 62 months ] [ Designated as safety issue: No ]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
|Study Start Date:||August 1999|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: 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).
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).
Other Name: ThalomidProcedure: 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.
Placebo Comparator: Arm 2 - Placebo once daily
Patients receive oral placebo once daily.
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
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00019747
|United States, Indiana|
|Center for Cancer Care at Goshen Health System|
|Goshen, Indiana, United States, 46526|
|United States, Maryland|
|Suburban Hospital Cancer Program|
|Bethesda, Maryland, United States, 20817|
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support|
|Bethesda, Maryland, United States, 20892-1182|
|United States, North Carolina|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|United States, Ohio|
|Charles M. Barrett Cancer Center at University Hospital|
|Cincinnati, Ohio, United States, 45267-0558|
|United States, Pennsylvania|
|UPMC Cancer Center at UPMC Presbyterian|
|Pittsburgh, Pennsylvania, United States, 15213|
|Study Chair:||Steven K. Libutti, MD||NCI - Surgery Branch|