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

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.