Clinical Trials /

Study of Drug 1 (Enzalutamide) Plus Drug 2 (Relacorilant) for Patients With Prostate Cancer

NCT03674814

Description:

The study is an open-label Phase 1 study of the combination of relacorilant with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC).

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Drug 1 (Enzalutamide) Plus Drug 2 (Relacorilant) for Patients With Prostate Cancer
  • Official Title: A Phase I Trial of Enzalutamide Plus the Glucocorticoid Receptor Antagonist CORT-125134 (Relacorilant) for Patients With Metastatic Castration Resistant Prostate Cancer (CRPC)

Clinical Trial IDs

  • ORG STUDY ID: IRB18-0152
  • SECONDARY ID: P50CA180995
  • NCT ID: NCT03674814

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
EnzalutamideXtandi(R)Dose Level
RelacorilantCORT-125134Dose Level

Purpose

The study is an open-label Phase 1 study of the combination of relacorilant with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC).

Detailed Description

      The study is an open-label Phase 1 study of the combination of relacorilant with enzalutamide
      in patients with metastatic castration resistant prostate cancer (mCRPC). Patients will be
      enrolled in 6 patient cohorts with a 6+3 design and a 28 day DLT period. Doses of
      relacorilant, enzalutamide will be adjusted based on safety and pharmacokinetics (PK). Once a
      safe dose with appropriate drug levels (PK) has been established, the cohort will be expanded
      to a total of 12 patients to refine safety and PK at the recommended phase II dose (RP2D).
    

Trial Arms

NameTypeDescriptionInterventions
Dose LevelExperimentalRelacorilant will be given at a dose once daily. Enzalutamide will be given at a dose once daily.
  • Enzalutamide
  • Relacorilant

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed prostate cancer with documented metastatic
             disease

          2. Evidence of castrate testosterone level <50ng/dl (or surgical castration)

          3. Evidence of disease progression:

               -  2 or more new lesions on bone scan or

               -  Progressive disease on CT/MRI according to Response Evaluation Criteria in Solid
                  Tumors 1.1 criteria or

               -  Rising Prostate Specific Antigen (PSA): PSA evidence for progressive prostate
                  cancer consists of a minimum PSA level of at least 2 ng/ml, which has
                  subsequently risen on at least 2 successive occasions, at least 2 weeks apart.

          4. Prior treatment with at least one line of potent androgen receptor signaling inhibitor
             (e.g. abiraterone, enzalutamide, apalutamide) in either castration-sensitive or
             castration-resistant setting.

          5. Any prior therapy for castrate disease is acceptable except prior GR antagonist
             treatment (e.g. mifepristone or relacorilant).

          6. Any other radiotherapy or radionuclide require 28-day washout prior to first dose of
             study drug.

          7. Denosumab or zoledronic acid are allowed.

          8. ECOG performance status ≤ 2.

          9. Patients must have normal hepatic function as defined below:

               -  Total bilirubin </=1.5 x the upper limit of normal

               -  AST(SGOT)/ALT(SGPT) </=2.5 X institutional upper limit of normal

               -  Albumin >/=3.0 g/dL

         10. Patients must have normal bone marrow function as defined below:

               -  Platelet count (plt) >/= 80,000 /microliter

               -  Hemoglobin (Hgb) >/= 9 g/dL

               -  Absolute neutrophil count (ANC) >/= 1500

         11. Patients must have normal renal function as defined below:

               -  GFR >/= 30 mL/min

         12. Ability to understand and the willingness to sign a written informed consent document.

         13. Patients with active Diabetes Mellitus on glucose lowering medications are eligible
             provided they agree to and are able to self-monitor daily blood glucose levels due to
             potential risk of lowering glucose levels on relacorilant.

         14. Male patient and his female partner who is of childbearing potential must use 2
             acceptable methods of birth control (one of which must include a condom as a barrier
             method of contraception) starting at screening and continuing throughout the study
             period and for 3 months after final study drug administration. Two acceptable methods
             of birth control thus include the following:

               -  Condom (barrier method of contraception); AND

               -  One of the following is required:

                    1. Established use of oral, or injected or implanted hormonal method of
                       contraception by the female partner;

                    2. Placement of an intrauterine device (IUD) or intrauterine system (IUS) by
                       the female partner;

                    3. Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps)
                       with spermicidal foam/gel/film/cream/suppository by the female partner;

                    4. Tubal ligation in the female partner;

                    5. Vasectomy or other procedure resulting in infertility (e.g., bilateral
                       orchiectomy), for more than 6 months.

        Exclusion Criteria:

          1. Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace),
             finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease
             PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid within 2
             weeks prior to first dose of study drug.

             a.Patients who have been on systemic corticosteroids with prednisone equivalent of
             10mg or greater for greater than 3 months immediately prior to participation in this
             study must have documented ability to tolerate cessation of corticosteroids prior to
             enrollment.

          2. Inability to swallow capsules or known gastrointestinal malabsorption.

          3. Evidence of visceral disease on imaging in a patient who is an appropriate candidate
             for cytotoxic chemotherapy (docetaxel or cabazitaxel).

          4. History of other malignancies, with the exception of: adequately treated non-melanoma
             skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 malignancies
             who are without evidence of disease, or other cancers curatively treated with no
             evidence of disease for > 5 years from enrollment.

          5. Blood pressure that is not controlled despite > 2 oral agents (SBP >160 and DBP >90
             documented during the screening period with no subsequent blood pressure readings
             >160/100).

          6. History of seizure disorder or active use of anticonvulsants. Medications used to
             treat neuropathic pain such as gabapentin or pregabalin are allowed.

          7. Documented history of or current brain metastases due to seizure risk

          8. Serious intercurrent infections or non-malignant medical illnesses that are
             uncontrolled.

          9. Active psychiatric illness/social situations that would limit compliance with protocol
             requirements.

         10. NYHA class II, NYHA class III, or IV congestive heart failure (any symptomatic heart
             failure).

         11. Concurrent therapy with strong inhibitors or inducers of CYP3A4 or CYP2C8 (See Section
             9.12below for list of strong inhibitor or inducers) due to concerning possible
             drug-drug interactions

         12. Presence of concurrent medical conditions requiring systemic glucocorticoids for
             immunosuppression (e.g. Autoimmune diseases, organ transplantation) that is active and
             has required glucocorticoids in the last 6 months.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Time Frame:28 days after start of dosing
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Preliminary anti-cancer activity of relacorilant as measured by prostate specific antigen levels per response evaluation criteria in solid tumors
Time Frame:12 weeks after initial start of combination dosing
Safety Issue:
Description:
Measure:Preliminary anti-cancer activity of relacorilant as measured by tumor response per response evaluation criteria in solid tumors
Time Frame:12 weeks after initial start of combination dosing
Safety Issue:
Description:
Measure:Assess steady state relacorilant drug levels when given with enzalutamide
Time Frame:28 days after start of dosing
Safety Issue:
Description:
Measure:Assess steady state enzalutamide drug levels when given with relacorilant
Time Frame:28 days after start of dosing
Safety Issue:
Description:
Measure:Radiographic progression free survival (PFS) of the combination
Time Frame:Approximately 3 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Chicago

Trial Keywords

  • prostate cancer
  • Enzalutamide
  • Relacorilant

Last Updated

November 13, 2018