1. A Phase II Trial of Perifosine in Patients with Chemo-Insensitive Sarcomas Study 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 – Toxicity N= ## Perifosine 100 mg daily Number of Events Grade Side Effect123 Nausea3651 Vomiting2843 Diarrhea6330 Anorexia500 Dyspepsia000 Constipation300 Decreased hemoglobin210 Fatigue771 Photosensitivity100 Fever400 Joint pain200

6. Participants (11) /Enrollment (72) Extra-Skeletal Myxoid Chondrosarcoma - 21 Conventional Chondrosarcoma - 37 Alveolar Soft Part Sarcoma - 14 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 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: Evaluate q 12 weeks Progression Perifosine 100 mg qhs daily Remove From Study SD, PR or CR Continue On Study Conventional Chondrosarcoma Extra-Skeletal Myxoid Chondrosarcoma Alveolar Soft Part Sarcoma

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 TotalEvaluable* PR (Choi) N (%) SD (> 12 wks) N (%) Off Study Progression Off Study Other Chondro 37331 (3%)9 (25%)2410 Extra-skeletal Myxoid 21 2 (10%)8 (38%)173 Alveolar Soft Part 14134 (29%)9 (64%)103 Total 72677 (10%)26 (36%)5116 * Evaluable: Pts receiving > 1 cycle of treatment All cohorts have met criteria to expand to full enrollment – 37 pts per arm Nov 28, 06: 1 st patient enrolledOct. 31, 08: 72 patients enrolled 23 mo’s + 11 sites

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