1 / 16

Joseph Ludwig, MD MD Anderson Cancer Center, Houston, TX

A PHASE II TRIAL OF PERIFOSINE IN PATIENTS WITH CHEMO-INSENSITIVE SARCOMAS A SARCOMA ALLIANCE FOR RESEARCH THROUGH COLLABORATION (SARC) STUDY Study Update – November 2007. Joseph Ludwig, MD MD Anderson Cancer Center, Houston, TX. Background & Rationale for Perifosine. Perifosine (NSC 639996).

mark-lynch
Download Presentation

Joseph Ludwig, MD MD Anderson Cancer Center, Houston, TX

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. A PHASE II TRIAL OF PERIFOSINE IN PATIENTS WITH CHEMO-INSENSITIVE SARCOMASA SARCOMA ALLIANCE FOR RESEARCH THROUGH COLLABORATION (SARC) STUDY Study Update – November 2007 Joseph Ludwig, MD MD Anderson Cancer Center, Houston, TX

  2. Background & Rationale for Perifosine Perifosine (NSC 639996) Preclinical: • Suspected interference with the plasma membrane (Leishmaniasis) • NCI (Evaluate first on PC-3 (mut PTEN) hyperactivated PI3K/Akt): reduced (p) Akt • Blocked effects in insulin, EGF, PDGF • Blocked localization of Akt to plasma membrane Phase I Studies: • Single agent, 2 of 10 (20%) of sarcoma patients responded (1 CS, 1 LMS) • With Gemcitabine 1 patient with CS had 17% reduction in tumor size. Phase II Studies (Single agent): • Mayo Clinic Phase II consortium - 1 PR (extra-skeletal myxoid) of 22 patients with STS The responses in a chondrosarcoma and a myxoid-chondrosarcoma are particularly notable because these tumors do not usually respond to cytotoxic chemotherapy

  3. Phase I Trials Sarcoma Responder - Wisconsin After 12 mo’s of 50 mg perifosine  52% decrease in size Van Ummersen et. al., Clinical Cancer Research, Vol. 10, Nov 15, 2004

  4. Patients with < 2 forms of prior chemotherapy stratified by Conventional Chondrosarcoma Extra-Skeletal Myxoid Chondrosarcoma Alveolar Soft Part Sarcoma P.S. (0-1) & Measurable, Progressive disease (Choi) Perifosine 100 mg qhs daily Evaluate q 3 months CR, PR, or SD Progression Continue On Study Remove From Study

  5. Objectives Primary • Evaluate the response rate defined by both Choi and RECIST criteria of single agent perifosine Secondary • Evaluate Time to Progression (TTP) • Evaluate the Clinical Benefit Rate (CR & PR + SD) • Continue to Monitor Drug Safety

  6. Major Inclusion / Exclusion Inclusion • Measurable Disease • Age > 13 years • ** Documented progression by Choi Criteria • Exclusion • > 2 prior cytotoxic regimens for metastatic disease (unless exempted)

  7. Study Population – 59 Patients • Gender: 35 Male / 24 Female • Median age: 51 (range 20 – 85) • Cycles on Treatment (1 – 9 cycles)

  8. Protocol 214 – ToxicityN = 43 Perifosine 100 mg Daily Common Perifosine Events

  9. 33 15 11 59 enrolled 10 31 17 Conventional Chondrosarcoma Extra-Skeletal Myxoid Chondrosarcoma Alveolar Soft Part Sarcoma Measurable progressive disease (Choi) Perifosine 100 mg qhs daily Evaluate q 12 weeks Off Study CR, PR, or SD Progression Continue On Study Remove From Study Enrollment Status since Nov. 28th, 2006; 12 sites open

  10. Current Enrollment Status Clinical Benefit Rate = 40% * Evaluable: Pts receiving > 1 cycle of treatment All cohorts have met criteria for full enrollment – 37 pts per arm

  11. Responses 1) 35 y/o female with ASPS Perifosine toxicities to date: • Grade 2 Nausea / Vomiting / Diarrhea / Fever Target Lesion: Right Manubrium • Baseline scan: 166.60 HU • 3 mo scan: 129.60 HU • 22% PR by Choi (SD by RECIST) 3) 69 y/o female with Conventional CS • Perifosine toxicities to date: • Well tolerated with limited toxicity Sum of Lesions: • Baseline scan: 185 HU • 3 mo scan: 120 HU • 6 mo scan: Pending • 35.2% PR by Choi (SD by RECIST) 2) 29 y/o female with ASPS Perifosine toxicities to date: Grade 2 Nausea / Vomiting / Abd. Pain Sum of Lesions: Baseline scan: 182.80 HU 3 mo scan: 146 HU 6 mo scan: 146 HU 20.13% PR by Choi (SD by RECIST)

  12. Response Criteria Difficulties • Unable to obtain HU’s on a few patients • Negative HU’s on one patient Eligibility Exceptions • Five patients had > 3 prior chemo regimens • One patient came off tx for 6 weeks for surgery and now back on after an initial response

  13. Interim Conclusions • Generally well tolerated • Common AE’s = GI related and fatigue • Criteria met to proceed to full study enrollment • Activity: Clinical Benefit (SD > 12 weeks) • Overall: 40% (19/48) • Chondro: 24% (PR = 4% by Choi) • ESMS: 54% (PR = 15% by Choi) • ASPS: 60% (PR = 30% by Choi) • Chondrosarcoma arm almost complete • 33 enrolled • 4 patients being screened

  14. Questions • Is the response rate of these sarcoma subtypes adequate to justify further study? • What is the Mechanism of action. • Does stable disease serve as a valid surrogate for improved survival.

  15. MD Anderson – 13 Dejka Araujo, MD Penn – 12 Arthur Staddon, MD Sarcoma Oncology – 11 Sant Chawla, MD MSKCC - 8 Robert Maki, MD Michigan - 5 Scott Schuetze, MD Mass General – 5 Edwin Choy, MD Fox Chase – 2 Margaret von Mehren, MD Washington Cancer – 2 Dennis Priebat, MD OHSU – 1 Christopher Ryan, MD Others Open: DFCI, Moffitt, UFL Participants (12) / Enrollment (59) Extra-Skeletal Myxoid Chondrosarcoma - 15 Conventional Chondrosarcoma - 33 Alveolar Soft Part Sarcoma - 11

  16. Increased reliance upon imaging Estimated *** Calculated delta Actual Tumor Size 0 3 6 9 12 15

More Related