Dejka Araujo, MD MD Anderson Cancer Center, Houston, TX

1. A Phase II Trial of Perifosine in Patients with Chemo-Insensitive SarcomasStudy Update – November 2008 Dejka Araujo, MD MD Anderson Cancer Center, Houston, TX

2. Protocol Design • Phase II study of perifosine in patients with: • Chondrosarcoma • Alveolar soft part sarcomas • Extra-skeletal myxoid chondrosarcomas • Perifosine 100 mg qhs

3. Objectives Primary • Evaluate the response rate defined by both Choi and RECIST criteria of single agent Perifosine Secondary • Evaluate Time to Progression • Evaluate the Clinical Benefit Ratio (SD of 6 mo’s or greater)

4. Major Inclusion/Exclusion Inclusion • Measurable Disease • Documented progression by Choi Criteria • Age > 13 years Exclusion • Patients who have received > 2 prior cytotoxic regiments for metastatic disease (unless approved as an exemption by the study chairman)

5. Protocol 214 – ToxicityN= ## Perifosine 100 mg daily

6. Participants (11) /Enrollment (72) MD Anderson – 15 • Dejka Araujo, MD Penn – 16 • Arthur Staddon, MD Sarcoma Oncology – 12 • Sant Chawla, MD MSKCC - 8 • Robert Maki, MD Michigan - 5 • Scott Schuetze, MD, PhD Mass General – 7 • Edwin Choy, MD Extra-Skeletal Myxoid Chondrosarcoma - 21 Conventional Chondrosarcoma - 37 Alveolar Soft Part Sarcoma - 14 Fox Chase – 2 • Margaret vonMehren, MD Washington Cancer – 2 • Dennis Priebat, MD OHSU - 5 • Christopher Ryan, MD Dana Farber - 1 • James Butrynski, MD Others Open: • Moffitt

7. Patient with < 2 forms of prior chemotherapy stratified by: Alveolar Soft Part Sarcoma Extra-Skeletal Myxoid Chondrosarcoma Conventional Chondrosarcoma Perifosine 100 mg qhs daily Evaluate q 12 weeks SD, PR or CR Progression Continue On Study Remove From Study

8. Study Population – 72 patients • 44 Male/ 28 Female • Median age: 51 (range 20 - 85) • Cycles on treatment • Minimum: 1 cycle • Max to date: 20 cycles • Patients off Study: • 51 off for disease progression • 5 off for intercurrent illness • 4 off for physician decision (possibly related to AE) • 4 off per patient request (unrelated to AE) • 3 off per Adverse Event

9. Current Enrollment Status 23 mo’s + 11 sites Nov 28, 06: 1st patient enrolled Oct. 31, 08: 72 patients enrolled * Evaluable: Pts receiving > 1 cycle of treatment All cohorts have met criteria to expand to full enrollment – 37 pts per arm

10. Response Criteria Difficulties • Unable to obtain HU’s on many patients • Negative HU’s on one patient

11. Eligibility Exceptions • One pt had elevated liver enzymes secondary to medication. Med stopped and enzymes returned to normal • One pt had no documented progression at time of entry because new lesion unable to be seen on imaging because pt allergic to contrast dye • 10 pts had > 3 prior chemo regimens • One pt had previous brain mets • One pt had documentation of progression > 3 months prior to enrollment d/t pt had debulking of chest wall • One pt had pre study hemoglobin Grade 3 toxicity • One pt had eligibility labs > 7 days prior to study start • One pt had Class II NYHA, d/t svs from cancer not cardiac history • CT chest scan done outside of study window

12. Protocol Deviations • Missing HUs on many patients • One pt with non-compliance regarding dosing • One pt with 1 month visit outside window • One pt with CT scans outside of window • One pt missed Cycle 8 and Cycle 9 d/t transportation problems

13. Conclusions to Date • Perifosine has been generally well tolerated- Common Grade 1/2 events are GI related • Criteria met to proceed to full study enrollment • Demonstrated activity: 36% (26/72) of patients achieving Clinical Benefit (SD > 12 weeks) • ASPS: 64% Clinical Benefit ( 29% PR by Choi) • ESMS: 38% Clinical Benefit (10% PR by Choi) • Chondro: 25% Clinical Benefit (3% PR by Choi) • Chondro arm enrollment complete