A Phase II Trial of Perifosine in Patients with Chemo-Insensitive

SarcomasStudy Update – November 2008

Dejka Araujo, MDMD Anderson Cancer Center, Houston, TX

Protocol Design

Phase II study of perifosine in patients with: Chondrosarcoma Alveolar soft part sarcomas Extra-skeletal myxoid chondrosarcomas

Perifosine 100 mg qhs

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)

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)

Protocol 214 – ToxicityN= ## Perifosine 100 mg daily

Number of EventsGrade

Side Effect 1 2 3Nausea 36 5 1Vomiting 28 4 3Diarrhea 63 3 0Anorexia 5 0 0Dyspepsia 0 0 0Constipation 3 0 0Decreased hemoglobin 2 1 0Fatigue 7 7 1Photosensitivity 1 0 0Fever 4 0 0Joint pain 2 0 0

Participants (11) /Enrollment (72)

Extra-Skeletal MyxoidChondrosarcoma - 21

ConventionalChondrosarcoma - 37

Alveolar Soft PartSarcoma - 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

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

ConventionalChondrosarcoma

Extra-Skeletal MyxoidChondrosarcoma

Alveolar Soft PartSarcoma

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

Current Enrollment Status

Total Evaluable*PR (Choi)

N (%)

SD (> 12 wks)

N (%)Off Study

Progression

Off StudyOther

Chondro 37 33 1 (3%) 9 (25%) 24 10

Extra-skeletal Myxoid

21 21 2 (10%) 8 (38%) 17 3

Alveolar Soft Part

14 13 4 (29%) 9 (64%) 10 3

Total 72 67 7 (10%) 26 (36%) 51 16

* Evaluable: Pts receiving > 1 cycle of treatmentAll cohorts have met criteria to expand to full enrollment – 37 pts per arm

Nov 28, 06: 1st patient enrolled Oct. 31, 08: 72 patients enrolled23 mo’s + 11 sites

Response Criteria Difficulties

Unable to obtain HU’s on many patients Negative HU’s on one patient

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

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

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