What Is a Phase I Clinical Trial?

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Audio and slides for this presentation are available on YouTube: http://youtu.be/NzJ_fvSxwGk

Sara Tolaney, MD, MPH, a breast oncologist with the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, gives an overview of phase I clinical trials and some of the new drugs being tested to treat breast cancer. This talk was originally given at the Metastatic Breast Cancer Forum at Dana-Farber on Oct. 5, 2013.

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What Is a Phase I Clinical Trial?

  1. 1. Phase I Clinical Trials Sara Tolaney, MD, MPH Breast oncologist Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute October 5, 2013
  2. 2. What are clinical trials? • Research studies that are designed to answer questions about new ways to treat cancer
  3. 3. What are the different types of clinical trials? Phase Purpose Phase I Determine dose Determine side-effects (Number of people: 15-20) Phase 2 Determine efficacy (Number of people: <100) Phase 3 Compare the new treatment to a standard treatment Number of people: 100-1000s)
  4. 4. Road To FDA Approval Preclinical Phase 1 Phase 2 Phase 3 FDA Approval
  5. 5. Goals of Phase 1 Clinical Trials • How much of a new drug can be given safely • How often the drug needs to be given • What are the side effects of the new drug
  6. 6. Types of Phase 1 Trials • Disease specific phase 1 studies • All-comer phase 1 trials open to any solid tumor • New agent alone • Combining new agents • Combining new agent with standard chemotherapy
  7. 7. Dose Escalation in Phase 1 Studies: 3+3 Design Once dose determined 30 mg 20 mg 10 mg 3 Patients 3 Patients 3 Patients EXPANSION COHORT Enroll 10-20 patients
  8. 8. Pharmacokinetics (PKs) • Tests how rapidly a drug is cleared from circulation • Challenging for patients because can sometimes require long days and multiple visits a week during the first cycle of therapy
  9. 9. Early Drug Development Center (EDDC) • Conducts research dedicated to studying new drugs • Specializes in phase I clinical trials • Has over 30 phase I studies, some of which are open to patients with all solid tumors, and a few of which are specific to breast cancer • You may be referred to the EDDC to discuss trial possibilities • If you go on a study, you will be followed within the EDDC, but will also continue to have your original oncologist/team involved in your care
  10. 10. Trials of Interest for Breast Cancer • BRCA Carriers – Rucaparib – Veliparib and Irinotecan – Sapacitabine and Seleciclib • ER+ Breast Cancer – Cdk 4/6 inhibitors • Triple-negative Breast Cancer – Mek/akt – Cdk/parp – PDL1 Antibody (immunotherapy)
  11. 11. PARP Inhibitors Igelhart JD and Silver DP. NEJM 2009
  12. 12. PARP Inhibitor Studies • Rucaparib – PARP inhibitor given alone • Veliparib + Irinotecan – PARP inhibitor given with chemotherapy • Olaparib + BKM120 – In breast cancer group, combines PARP with PI3K inhibitor
  13. 13. Sapacitabine + Seleciclib • Sapacitabine: oral chemotherapy • Seleciclib: oral cdk 1,2, 7, 9 inhibitor
  14. 14. CDK 4/6 Inhibitors
  15. 15. Progression-Free Survival Progression-Free Survival Probability PD 991 + LET (n = 84) LET (n = 81) 1.0 Number of Events (%) 21 (25) 40 (49) 0.9 Median PFS, months (95% CI) 26.1 (12.7, 26.1) 7.5 (5.6, 12.6) 0.8 Hazard Ratio (95% CI) 0.7 P value 0.37 (0.21, 0.63) <0.001 0.6 0.5 0.4 0.3 0.2 0.1 0 0 2 4 6 8 10 84 81 75 57 60 38 14 16 18 20 22 24 26 14 4 9 3 5 3 3 1 1 1 Time (Month) Number of patients at risk PD991+LET LET 12 53 29 43 22 35 17 25 11 18 6 15 5 28
  16. 16. Ongoing studies with cdk 4/6 inhibitors • LEE011 – Cdk 4/6 inhibitor given alone, in expansion phase • Lilly cdk 4/6 inhibitor + faslodex
  17. 17. Triple-negative Breast Cancer • PI3K inhibition – GDC-0973/GDC-0068 (MEK/Akt inhibitors) – BKM120 (phase 2) • Dinaciclib/Veliparib – Cdk + PARP • Immunotherapy – PDL1 Antibody
  18. 18. Conclusions • Exciting time in drug development • Several phase I clinical trial options for patients with varying subtypes of breast cancer • Many trials require tissue prescreening with a goal of trying to deliver personalized medicine
  19. 19. Common Questions
  20. 20. Will I get a placebo?
  21. 21. • No-- phase I trials do not administer placebos
  22. 22. How often will I need to come in for visits?
  23. 23. • Each trial is different, but generally most phase I studies have at least weekly visits for the first cycle (3-4 weeks) then fewer visits thereafter
  24. 24. How will you know if the drug is working?
  25. 25. • Frequency of imaging is dependent on the study, but generally every 6-9 weeks
  26. 26. Why should I do a clinical trial?
  27. 27. Weigh Pros and Cons Pros: • If a new treatment is proven to work and you are receiving it, you may be among the first to benefit • You can expand the number of treatment options you have • You have a chance to help others and improve cancer care Cons: • New treatments may have side effects that doctors do not expect • Phase I trials often involve frequent visits during the first cycle • Even if a new treatment has benefits, it may not work for you
  28. 28. Will my insurance pay for me to participate in the trial?
  29. 29. • Generally, almost all insurance companies pay for patients to participate in phase I clinical trials • Anything that is for research purposes (ie. research blood, biopsies) is provided by research • Experimental medication is provided

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