ProSTAR: A Phase 1b/2 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Combined with Enzalutamide or Abiraterone/Prednisone in Patients with Metastatic Castration Resistant Prostate Cancer (Protocol 1205-201)
Johns Hopkins Kimmel Cancer Center in Baltimore
The research purpose is to find out if an investigational drug called CPI-1205 can help men with metastatic castration resistant prostate cancer (CRPC). The study drug, CPI-1205, will be administered alone or with cobicistat, combined with enzalutamide or abiraterone/prednisone. Cobicistat is an FDA approved drug to increase the amount of medications in the blood.The study has two parts, Dose Escalation (Part A) will determine a recommended dose of CPI-1205/cobicistat + enzalutamide or abiraterone/prednisone, and Part B, which will evaluate the effectiveness of the combination (CPI-1205/with or without cobicistat plus enzalutamide, OR abiraterone/prednisone) You will only be able to participate in one, depending on which part is open when you are being asked to participate. If you have previously been treated with Enzalutamide, you will be assigned to CPI-1205/cobicistat + abiraterone/prednisone. If you have previously been treated with abiraterone/prednisone, you will be assigned to CPI-1205/with or without cobicistat + enzalutamide.
Inclusion:1.Confirmed adenocarcinoma of the prostate. 2.Documented metastatic disease may be non-measurable in Phase 1 where safety/tolerability is assessed, or must be measurable in phase 2.3.Must have undergone bilateral orchiectomy (surgical castration) or be willing to continue GnRH analog or antagonist (medical castration).4.Serum testosterone less than 50 ng/dL5.In Phase 1b and 2, progressive disease measured by increase in PSA in the setting of medical or surgical castration less than 6 months from end of last therapy AND/OR 6.Soft tissue disease progression as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 AND/OR7. Bone disease progression defined by two or more new lesions on bone scanIn addition, patients enrolled in Phase 2 must have at least one of the following:8.Measurable disease AND/OR9.Unfavorable CTC statusExclusion:1. Known symptomatic brain metastases unless it has been treated.2. Receipt of greater than 1 line of therapy that includes a second generation androgen inhibitor for treatment of mCRPC3. Treatment with any of the following for prostate cancer within 4 weeks prior to day 1 of treatment: AR antagonists such as bicalutamide, alpha reductase inhibitors, such as ketoconazole, estrogens and progesterone.4. Chemotherapy5. Biologic therapy6. Saw palmetto or other therapies with endocrine effects on prostate cancer7. Other Investigational therapy 8. Immunotherapy9. Prior radiation therapy or radionuclide therapy for the treatment of metastasis10. Herbal products that may decrease PSA levels within 4 weeks prior to day 1 of treatment11. Systemic steroids greater than the equivalent of 10 mg. of prednisone/prednisolone per day within 4 weeks prior to day 1 of treatment 12. Major surgery within 4 weeks prior to day 1 of treatment13. Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery14. Structurally unstable bone lesions concerning for impending fracture15. Clinically significant cardiovascular disease including:16. Myocardial infarction (MI)/Stroke within 6 months prior to day 1 of treatment17. Uncontrolled angina within 3 months18. Congestive heart failure (CHF) with New York Heart Association.This is not an exhaustive list, there may be other factors that will eliminate you.
The study has 2 parts: Dose Escalation (Part A) and Dose Expansion (Part B). If you join Part A, you will be assigned a dose level of CPI-1205 that you will take by mouth up to three times daily (each tablet contain 200 mg of CPI-1205 each). The total amount of tablets will vary, based on when you join the study. You will also be assigned a fixed dose of cobicistat as well as a dose of either enzalutamide or abiraterone/prednisone to take in combination with your CPI-1205. The fixed dose of cobicistat is 150 mg tablet, which you will take by mouth twice per day. The fixed dose of enzalutamide is 160 mg, which you will take by mouth once daily. This will come in capsule form, with each capsule containing 40 mg (that is, you will take four 40 mg capsules once per day.) The fixed dose of abiraterone is 1000 mg, which you will take by mouth once daily. This will come in tablet form, with each tablet containing 250 mg (that is, you will take four 250 mg tablets once per day.If you agree to be in this study, you will have to come to the study center:• at least one time during screening• up to 6 times during Cycle 1• three to four times during Cycle 2• two times during Cycle 3• 1 time for Cycle 4 and each subsequent cycle• At least two times for Follow up Visits
03/05/2019 05:03 AM