A Randomized Phase II Trial of Neoadjuvant Enzalutamide Plus the Glucocorticoid Receptor Antagonist Relacorilant Versus Placebo for Patients With High-risk Localized Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- Relacorilant
- Conditions
- Prostate Cancer
- Sponsor
- University of Chicago
- Enrollment
- 90
- Locations
- 2
- Primary Endpoint
- Response Rate of Subjects Receiving Relacorilant with Enzalutamide and Hormone Therapy
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
Researchers conducting this study hope to learn about the safety and effectiveness of combining two study drugs, relacorilant and enzalutamide, plus androgen deprivation therapy (ADT), also known as hormone therapy. This study is for individuals who have been diagnosed with advanced, high-risk prostate cancer and standard therapies available to treat your disease have not been effective. Participation in this research will last about 3 years and 9 months.
Detailed Description
The purpose of this research is to gather information on the safety and effectiveness of combining two study drugs (relacorilant and enzalutamide) with hormone therapy. Doctors leading this study hope to learn if combining these study drugs with hormone therapy is safe and could improve the results of surgery and delay the time to when prostate cancer tumors spread to other parts of the body in individuals with advanced, high-risk prostate cancer who plan to receive a radical prostatectomy (surgical removal of the whole prostate and surrounding tissue). Prostate cancer cells usually need hormones (called androgens) to grow. One of these hormones is testosterone, which is mostly produced in the testicles. The usual approach for treating prostate cancer after it progresses involves taking medications to decrease or block the development of hormones (including testosterone) so that prostate cancer cells can't continue to grow. This approach is called androgen deprivation therapy (hormone therapy). Enzalutamide is a hormone-blocking medication, which is a standard of care for prostate cancer when it spreads (metastasizes).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed prostatic adenocarcinoma without primary small cell histology
- •Localized disease:
- •Surgical resectability must be documented prior to enrollment
- •No evidence of distant metastatic disease on abdominopelvic imaging, bone imaging
- •Enlarged lymph nodes below the iliac bifurcation (clinical stage N1) is allowed
- •Either cross-sectional abdominopelvic imaging + technetium bone scan or PSMA PET imaging will be acceptable to rule out distant metastatic disease
- •High or very high-risk disease (https://www.nccn.org/professionals/physician\_gls/pdf/prostate.pdf) as defined by having one or more of the following:
- •Clinical T3a or higher
- •Histologic Grade Group 4 or 5
- •Eastern Cooperative Oncology Group performance status ≤ 1 (Appendix A)
Exclusion Criteria
- •Therapy with ANY hormonal therapy for prostate cancer (prior 5-alpha-reductase inhibitors for benign prostate disease is allowed but must be discontinued prior to study initiation).
- •Inability to swallow capsules or known gastrointestinal malabsorption.
- •History of other malignancies, with the exception of: adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 malignancies that are without evidence of disease, or other cancers curatively treated with no evidence of disease for \> 5 years from enrollment.
- •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).
- •History of seizure disorder or active use of anticonvulsants. Medications used to treat neuropathic pain such as gabapentin or pregabalin are allowed.
- •Serious inter-current infections or non-malignant medical illnesses that are uncontrolled.
- •Active psychiatric illness/social situations that would limit compliance with protocol requirements.
- •New York Heart Association (NYHA) class II, class III, or IV congestive heart failure (any symptomatic heart failure).
- •Concurrent therapy with strong inhibitors of Cytochrome P450 3A4 or CYP2C8 due to concerning possible drug-drug interactions.
- •Concurrent therapy with strong inducers of Cytochrome P450 3A4 due to concerning possible drug-drug interactions.
Arms & Interventions
Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide
All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/relacorilant with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).
Intervention: Relacorilant
Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide
All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/relacorilant with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).
Intervention: Enzalutamide
Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide
All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/relacorilant with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).
Intervention: Androgen Deprivation Therapy
Group 1: Participants Who Receive Study Drug (Relacorilant) with Hormone Therapy and Enzalutamide
All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/relacorilant with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).
Intervention: Radical Prostatectomy
Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide
All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/placebo (sugar pill in the form of 2 softgel capsules) with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).
Intervention: Enzalutamide
Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide
All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/placebo (sugar pill in the form of 2 softgel capsules) with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).
Intervention: Placebo (Sugar Pill)
Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide
All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/placebo (sugar pill in the form of 2 softgel capsules) with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).
Intervention: Androgen Deprivation Therapy
Group 1: Participants Who Receive Placebo (no study drug) with Hormone Therapy and Enzalutamide
All participants in this group will have surgery up to 4 weeks after receiving enzalutamide/placebo (sugar pill in the form of 2 softgel capsules) with hormone therapy. A radical prostatectomy (removal of the prostate and any surrounding tissue that the surgeon thinks may be affected by the cancer).
Intervention: Radical Prostatectomy
Outcomes
Primary Outcomes
Response Rate of Subjects Receiving Relacorilant with Enzalutamide and Hormone Therapy
Time Frame: 24 weeks
To determine if relacorilant (Rela) when added to androgen receptor signaling inhibition (ARSI) with enzalutamide (Enz) and androgen deprivation therapy (ADT) improves response rate compared to relacorilant with enzalutamide and ADT using both concurrent and historical controls. This outcome will be measured by assessing pathologic complete response rate (pCR) plus minimal residual disease (MRD) at radical prostatectomy (RP) after 24 weeks of neoadjuvant therapy.
Secondary Outcomes
- • To determine the 3-year biochemical recurrence-free survival (bRFS) and metastasis-free survival (MFS) rate with combination hormonal therapy with Rela + ARSI with Enz compared to ARSI with Enz alone(3 years and 9 months)
- Radiographic Response Rate(3 years and 9 months)