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
I. Determine the treatment delivery and toxicity of the combination of thalidomide and
radiotherapy in patients with low-grade primary soft tissue sarcoma of the extremity or body
II. Determine the treatment delivery and toxicity of the combination of thalidomide and
doxorubicin, ifosfamide, dacarbazine, and radiotherapy in patients with high- or
intermediate-grade primary soft tissue sarcoma of the extremity or body wall and compare
these results with those of patients treated on RTOG-9514.
III. Determine the feasibility of using specific tissue and circulating biomarkers of
antiangiogenic response in patients treated with these regimens, in a multi-institutional
IV. Determine the quantitative changes and patient variabilities of these biomarkers before,
during, and after therapy with these regimens.
V. Determine the baseline data sets of biomarkers, particularly circulating endothelial
cells, in patients treated with these regimens.
VI. Determine the tolerance to long-term post-operative thalidomide in these patients.
VII. Determine the clinical response to pre-operative therapy in these patients.
VIII. Correlate local control and disease-free survival with surrogate biological endpoints
in patients treated with these regimens.
OUTLINE: This is a pilot, cohort study. Patients with high- or intermediate-grade tumors >=
8 cm in diameter are assigned to cohort A and patients with low-grade tumors > 5 cm in
diameter are assigned to cohort B.
Cohort A: Patients receive doxorubicin, ifosfamide, and dacarbazine IV continuously on days
1-3, 22-24, and 43-45. Patients receive filgrastim (G-CSF) subcutaneously beginning on days
4, 25, and 46 and continuing until blood counts recover. Patients undergo radiotherapy once
daily on days 7-11, 14-18, 21, 28-32, 35-39, and 42. Patients receive oral thalidomide once
daily on days 7-21 and 26-42. Patients undergo surgical resection between days 84 and 98.
Beginning 2 weeks after surgery, patients receive oral thalidomide once daily for 12 months
in the absence of unacceptable toxicity.
Cohort B: Patients receive oral thalidomide once daily beginning on day 1 and continuing
until 1 week before surgery. Patients undergo radiotherapy once daily, 5 days a week, on
weeks 1-5. Patients undergo surgical resection between days 77 and 91. Beginning 2 weeks
after surgery, patients receive oral thalidomide once daily for 6 months in the absence of
Patients are followed every 3 months for 2 years and then every 6 months for 4 years.
PROJECTED ACCRUAL: A total of 44 patients (22 per cohort) will be accrued for this study
within 17 months.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Treatment delivery with compliance defined as receiving at least 95% of the pre-operative protocol dose of RT, all 3 cycles of MAID (if applicable), and receive thalidomide on 75% of the days during radiation
Will be estimated using a binomial distribution and accompanied by the associated 95% confidence interval.
Up to 6 years
Radiation Therapy Oncology Group
United States: Food and Drug Administration
|Radiation Therapy Oncology Group||Philadelphia, Pennsylvania 19107|