Protocol Title:

A Pilot Phase II Study of Pre-Operative Radiation Therapy and Thalidomide (IND 48832; NSC 66847) for Low Grade Primary Soft Tissue Sarcoma or Pre-Operative Maid/Thalidomide/Radiation Therapy for High/Intermediate Grade Primary Soft Tissue Sarcoma of the Extremity or Body Wall.

Protocol Status:

Closed

Protocol Number:

R 0330

Type of Cancer:

Sarcoma

Principal Investigator :

David Ettinger, MD

Research Nurse:

Shirl DiPasquale, RN

Phase Number:

II

General Eligibility:

The patient must have a primary T2a or T2b soft tissue sarcoma located on the upper extremity (including shoulder), the lower extremity (including hip), or trunk. Patients with locally recurrent sarcoma are eligible provided there is no evidence of metastatic disease and there has been no prior radiation therapy to the primary site. Tumor > 8.0 cm in maximal diameter and Grade 3 or 4 (intermediate to high grade) for Cohort A; Tumor > 5 cm in maximal diameter and Grade 1 or 2 (low grade) for Cohort B. Age > 16 years; Zubrod performance status must be 0-1.

For Cohort A, normal heart function (study showing EF > 50% within past six months prior to registration). Men taking thalidomide must use latex condoms every time they have sex with women during therapy and for 4 weeks after discontinuing thalidomide. A female patient of childbearing potential must be reliable in carrying out instructions, be capable of complying with mandatory contraceptive measures, be willing to either abstain from all reproductive sexual intercourse or use 2 methods of birth control for 4 weeks after discontinuing thalidomide therapy. In addition, she must receive both spoken and written warnings of the hazards of taking thalidomide during pregnancy as well as the risk of contraception failure and must acknowledge her understanding of these warnings in writing. Patients must sign a study-specific informed consent, which includes mandatory use of tissue for central review.

Purpose:

Primary:
• To assess treatment delivery and toxicity of combination treatment for soft tissue sarcoma (STS) utilizing thalidomide in each patient cohort. For high/intermediate grade cohort A, the results will be compared to RTOG 95-14.
Secondary:
• To assess the feasibility of using specific tissue and circulating biomarkers of antiangiogenic response in a multi-institutional setting.
• To assess quantitative changes and patient variabilities of these biomarkers before, during, and after therapy in each patient cohort.
• To assess tolerance of long term post-operative adjuvant thalidomide in each patient cohort.
• To assess chemical response to pre-operative therapy in each patient cohort.
• To assess local control and disease-free survival relative to surrogate biological endpoints in each patient cohort.

Treatment:

Patients randomized to Cohort A will receive neoadjuvant MAID (Mesna, Doxorubicin, Ifosfamide, DTIC) for 3 cycles with concurrent thalidomide and radiation therapy (RT) x 2 cycles. Followed by surgical resection and adjuvant thalidomide for 12 months (post operative boost RT if positive surgical margins

Those randomized to Cohort B will receive neoadjuvant concurrent thalidomide and RT, continue thalidomide until 1 week prior to surgery followed by surgical resection and adjuvant thalidomide for 6 months