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Sipuleucel T Presentation Anna Begelfer Ostrovski


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Sipuleucel T Presentation Anna Begelfer Ostrovski

  1. 1. Placebo-Controlled Phase III Trial of Immunologic Therapy with Sipuleucel-T (APC8015) in Patients with Metastatic, Asymptomatic Hormone Refractory Prostate Cancer<br />Eric J. Small, Paul F. Schellhammer, Celestia S. Higano, Charles H. Redfern, John J. Nemunaitis, Frank H. Valone, Suleman S. Verjee, Lori A. Jones, Robert M. Hershberg<br />By Anna Begelfer-Ostrovski<br />BPHE5310P-000M: Clinical Trials Overview, Spring 2011<br />
  2. 2. Starts in the prostate gland<br />Wraps around the urethra (the tube that carries urine out of the body.) <br />Third common cause of death from cancer in man of all ages.<br />First most common cause of death from cancer in man over 75 of age. <br />Rarely found in man younger than 40. <br />Highest risk: Man over 60. <br />Prostate cancer:<br />
  3. 3. Prostate cancer:<br />
  4. 4. patient specific therapeutic cancer vaccine for prostate cancer.<br />Manufactured by a company named Dendreon. <br />Was approved by the FDA on April 29, 2010 to treat asymptomatic or minimally symptomatic metastatic Hormone refractory prostate cancer. <br />Sipuleucel-T:<br />
  5. 5.  <br />1. Patient’s own white blood cells with antigen presenting cells (APC) are extracted. (Those cells called Dentritic therefore the company name is Dendreon). <br />Preparation of treatment vaccine Sipuleucel-T<br />
  6. 6. 2. The cells are incubated with fusion protein (PA2024) consist of:<br /><ul><li>Prostatic Acid Phosphate (PAP)- present at most prostatic cancer cells.
  7. 7. immune signaling factor (GM-CSF) that helps the APCs to mature.</li></ul>Preparation of Sipuleucel-T:<br />
  8. 8.
  9. 9. Identifier:NCT01133704<br />Purpose: <br /> stimulate T-cell immunity against prostatic acid phosphatase.<br />evaluate the safety and efficacy of sipuleucel-T in a placebo-controlled study.<br />Clinical trial overview:<br />
  10. 10. PAP- not found in non prostate tissue.<br />Patients who developed a natural immune response to PAP had a longer disease progression: 34 weeks vs 13 weeks <br />Background to trial design:<br />
  11. 11. 1. Overall Time to Disease Progression<br />Time frame: 36 months<br />Asymptomatic patients compare to placebo. <br />2. Overall Survival<br />Subjects were followed for 3 years from the time of randomization or until death.<br />Primary Outcome Measures:<br />
  12. 12. 127 patients with asymptomatic metastatic hormone refractory prostate cancer.<br />2:1 ratio to receive three infusions of sipuleucel-T (n = 82) or placebo (n = 45) every 2 weeks.<br />PATIENTS AND METHODS:<br />
  13. 13. 19 centers in the United States.<br />Patients with histologically confirmed adenocarcinomaof the prostate.<br />Radiologic evidence of metastases.<br />Serum testosterone less than 50 ng/dL.<br />Expected survival of at least 3 months.<br />Recruitment for trial:<br />
  14. 14. Prior radiation must be completed at least one month before  trial treatment.<br />Radiation is prohibited within 1 year of treatment.<br />Patients with prior immunotherapy were not eligible to participate.<br />Patients with cancer-related bone pain or with visceral metastasis were not permitted.<br />Recruitment for trial continuous:<br />
  15. 15. 2:1 ration T cells- placebo.<br />Treatment was given on weeks: 0, 2, 4<br />Freshly prepared T cells and placebo vaccine for each treatment.<br />Acetaminophen (650 mg) was given 30 minutes prior to injection.<br />Treatment administration:<br />
  16. 16. Patients were observed every 8-12 weeks after treatment.<br />Examination performed:<br />Physical examination.<br />Adverse event assessment.<br />Laboratory tests.<br />Radiographic imaging.<br />Pain assessment.<br />Following up with patients:<br />
  17. 17. progressive disease on serial radiographic imaging tests.<br />new cancer-related pain associated with a radiographic anatomic correlation.<br />progression such as spinal cord compression, nerve root compression, or pathologic fracture. <br />Trial End Points:<br />
  18. 18. Increase greater than 50% in measurable disease.<br />Clear worsening of nonmeasurable disease.<br />Appearance of at least two new lesions on a bone scan.<br />Development of cancer-related pain that correlated with a site of metastasis.<br />Development of other clinical events consistent with progression.<br />Progressive disease defined: <br />
  19. 19. Attaining a power of 80%.<br />Two-sided .05 significance level.<br /> Assumption: sipuleucel-T result in an increase in median TTP to 7.7 months.<br />Loss to follow-up rate of 5%.<br />Enrollment of approximately 120 patients was targeted to achieve the required 80 events.<br />Statistical Considerations:<br />
  20. 20. Patient Disposition:<br />
  21. 21. Clinical Results: <br />Primary end point, time to disease progression<br />
  22. 22. Final overall survival<br />Clinical Results: <br />
  23. 23. Immune Monitoring:<br />The PA2024 T-cell stimulation index is a measure of specific T-cell responsiveness against the target antigen.<br />Toxicity:<br />significantly more common in sipuleucel-T treated patients.<br />*No patient discontinued the trial because of toxicity. <br />Other measurments:<br />
  24. 24. Of the 127 patients, 115 patients had progressive disease at the time of data analysis.<br />The median for time to disease progression (TTP) for sipuleucel-T was 11.7 weeks vs 10.0 weeks for placebo.<br />Median survival was 25.9 months for sipuleucel-T and 21.4 months for placebo.<br />Final results:<br />
  25. 25. The improvement in the primary end point TTP did not achieve statistical significance.<br />Study suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients.<br />Need for further supportive studies.<br />Conclusion<br />
  26. 26.  At 36 months, the estimated survival rate in the sipuleucel-T group was 34 weeks compared with 11 weeks in the placebo group.<br />The real numbers were 25.9 vs 21.4.<br />provide a survival advantage to asymptomatic HRPC patients. <br />no patients were removed from the trial for toxicity.<br />no treatment-related deaths.<br />Need for supportive studies?<br />
  27. 27. Feel free to contact me:<br /><br />917-478-1063<br />Questions? <br />