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Adjuvant Therapy and Clinical Trials

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Presented by Sapna Patel, MD. Presented at the 2018 Eyes on a Cure: Patient & Caregiver Symposium, hosted by the Melanoma Research Foundation's CURE OM initiative.

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Adjuvant Therapy and Clinical Trials

  1. 1. ADJUVANT THERAPY AND CLINICAL TRIALS Sapna Patel, M.D. Melanoma Medical Oncology 7th Annual Eyes on a Cure: Ocular Melanoma Patient and Caregiver Symposium April 21, 2018
  2. 2. ADJUVANT THERAPY
  3. 3. Two definitions • Treatment given to prevent recurrence or spread of cancer • Secondary prevention • Vaccine-modifying agent • MMR: Aluminum-based • Cancer vaccines: water-in-oil emulsions
  4. 4. Adjuvant Trial Design: How do we do this?
  5. 5. High-Risk Patients Intervention RFS/OS 3yr DMFS Single-arm 33-135 Patients
  6. 6. High-Risk Patients Intervention RFS/OS 3yr DMFS Observation RFS/OS 3yr DMFS 1:1 Randomization 135-544 Patients R
  7. 7. High-Risk Patients Intervention RFS/OS 3yr DMFS Observation RFS/OS 3yr DMFS 2:1 Randomization 145-599 Patients R
  8. 8. High-Risk Patients c-met inhibitor RFS/OS 3yr DMFS MEK inhibitor RFS/OS 3yr DMFS HDAC inhibitor RFS/OS 3yr DMFS Immune therapy RFS/OS 3yr DMFS Multi-arm Randomization 700-800 Patients R
  9. 9. Appropriate Adjuvant Therapies Trial Design Targets High-risk Population
  10. 10. Interferon for Uveal Melanoma Stefan Dithmar, MD; Dario Rusciano, PhD; Michael J. Lynn, MS; David H. Lawson, MD; Cheryl A. Armstrong, MD; Hans E. Grossniklaus, MD 2-year course of IFNa • 3 MIU subq TIW • Initiated within 3 years of primary tx n = 121 patients • >= 65 years od • LTD >= 15 mm • Ciliary body involvement • Extrascleral extension 118 pts tx with proton 3 pts tx with enucleation 55 patients completed tx Median f/u 9.5 years No difference in melanoma-related mortality c/w matched controls
  11. 11. Adjuvant DTIC plus IFNa in High Risk UM • Iris, Ciliary Body, or Choroid melanoma • Monosomy 3 • Completed primary therapy, no distant disease • Enrolled within 56 days (8 weeks) of primary therapy • DTIC 850 mg/m2 IV Day 1 and Day 28 • IFNa 3 million IU SQ TIW x 24 weeks beginning Week 9 Awaiting results
  12. 12. High-risk UM Class 2 or Mono 3 + Apical>=8mm Ipilimumab 3mg/kg (n=3 to 6) induction Ipilimumab 10 mg/kg (n=31 to 35) induction Ipilimumab Maintenance Weeks 24, 36, 48 Phase I/II Study: Ipilimumab (Adjuvant Therapy) for high-risk UM Original N = 89
  13. 13. Patient Date of first Ipi Dose of Ipi Doses (max = 7) Grade 3/4 AEs Reason 1 03/2013 3 mg/kg 7 Colitis Completed 1 year 2 03/2013 3 mg/kg 7 ALT/AST Completed 1 year 3 04/2013 3 mg/kg 6 Rash, Pruritus Completed 1 year 4 05/2013 10 mg/kg 7 Pruritus Completed 1 year 5 05/2013 10 mg/kg 2 Vasculitis SAE 6 05/2013 10 mg/kg 2 Colitis, ALT, AST SAE 7 06/2013 10 mg/kg 7 ____ Completed 1 year 8 07/2013 10 mg/kg 6 Adrenal Insuff Completed 1 year 9 07/2013 10 mg/kg 7 ALT/AST Completed 1 year 10 09/2013 10 mg/kg 7 ____ Completed 1 year
  14. 14. Hepatic radiation • Mon-Fri x 20 minutes for up to 10 fractions over 2 weeks • Planned enrollment of 50 patients Terminated after 1 year for slow enrollment
  15. 15. Peptide vaccine • MART-1, gp100, Tyr, NA17-A • Planned enrollment of 600 patients randomized to vaccine or observation Terminated for slow enrollment
  16. 16. Current Adjuvant Uveal Melanoma Trials • Crizotinib (n=30 in 2014, changed to 10 in 2016) – Class 2 tumors and LTD >=12 mm – 90 day window from primary tx – 48 weeks of treatment • Sunitinib or valproic acid (n=90) – Monosomy 3 + 8q amplification –or- Class 2 tumors – 180 day window from primary tx – 6 months of treatment
  17. 17. Future options • Adjuvant peptide vaccine • Adjuvant nivolumab + ipilimumab • Immunocore IMC gp100 (HLA*A:0201)
  18. 18. Laboratory based trials • HDAC inhibitor assays • Liquid biopsy • Microbiome
  19. 19. Trials versus Off-protocol Clinical Trials Pros • Covered by insurance • Study drugs are free • Science-driven • Research RN as a point person • Side effects captured Cons • Frequent visits • Compliance rules • Strict eligibility criteria • Discontinuation of study / drug Off-Protocol Pros • Liberal inclusion • Flexible schedule Cons • Not always supported by insurance • Costly drugs • Data outputs • Side effects not captured as methodically • No point person
  20. 20. ACKNOWLEDGEMENTS • Patients and Families who participate in clinical trials • Faculty, Staff, Researchers at MD Anderson Cancer Center • Collaborators outside MD Anderson • Melanoma and Skin Center: (713) 563-9716

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