1. Current RTOG Soft Tissue Sarcoma Trials
A Phase II Trial of Neoadjuvant/Adjuvant STI-571 (Gleevec) for Primary and Recurrent Operable Malignant GIST Expressing the KIT Receptor Tyrosine Kinase
0330
A Pilot Phase II Study of Pre-operative Radiation Therapy and Thalidomide 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

2. RTOG S-0132 baseline PET/CT/core biopsies Gleevec 600mg/day
repeat PET/CT 1-7 days
repeat PET/CT at 4 and 8 weeks
surgery if not responding or after 8 weeks
Gleevec 600mg/day for 2 years

3. RTOG S-0132 opened 2/2002 accrual target- 63 accrual to date- 55
objectives
response rates to Gleevec prior to surgery
recurrence free survival
biologic endpoints (KIT mutational analysis, tumor differences pre/post therapy)

4. RTOG 0330
based upon experience with RTOG 9514 but with additional new questions/endpoints
toxicity issues of 9514
benefit of addition of agent with alternative mechanism of action
biologic endpoints
incorporation of low grade tumors

5. RTOG 0330: Objectives local control and disease-free survival
relationship to surrogate biological endpoints
treatment delivery/toxicity of combination treatment utilizing thalidomide
tolerance of long term post-operative adjuvant thalidomide
feasibility of employing specific tissue and circulating biomarkers of antiangiogenic response in a multi-institutional setting
quantitative changes and patient variation in these biomarkers before, during, and after therapy
to develop baseline data sets of biomarkers, particularly circulating endothelial cells, for future study design for combined antiangiogenic therapy

6. Rationale for Thalidomide
immunomodulatory agent
antiangiogenic properties
potential relationship to circulating levels of bFGF and VEGF
these appear to be elevated in patients with STS
frequently used in combination therapy
well tolerated
oral agent

7. Cohorts for RTOG 0330 Cohort A
high/intermediate grade (histologic grade 3 or 4)
tumor ≥ 8 cm in greatest dimension
Cohort B
low grade (histologic grade 1or 2)
tumor > 5 cm in greatest dimension

8. Cohort A MAID Goal accrual: 22 patients XRT/ 12 mos THAL Surgery
+/- boost
XRT/THAL
12 mos
neoadjuvant MAID (Mesna, Doxorubicin, Ifosfamide, DTIC) x 3 cycles, concurrent thalidomide and radiation therapy (XRT) x 2 cycles, followed by surgical resection, followed by adjuvant thalidomide for one year (post-op boost XRT if positive margin)
Goal accrual: 22 patients

9. Cohort B Goal accrual: 22 patients XRT/ THAL THAL until surgery
+/- boost
XRT/THAL
6 mos
neoadjuvant concurrent thalidomide and XRT (stop thalidomide 1 week prior to surgery), followed by surgical resection, followed by adjuvant thalidomide for 6 months (post-op boost XRT if positive margin)
Goal accrual: 22 patients

10. RTOG 0330 opened 4/2004 accrual target- 44 (22 A/ 22 B)
accrual to date- 12 (6 A/ 6 B)