Comeback From Long coursE Androgen Deprivation Therapy (ADT) With RElugolix and Darolutamide (CLEARED)
NCT Number: NCT06463457
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Prostate Cancer|Advanced Prostate Cancer|Hormone Sensitive Prostate Cancer
Interventions: DRUG: Darolutamide|DRUG: Relugolix
Sponsor: Atish Choudhury, MD
Collaborators: Bayer|Pfizer|Sumitomo Pharma America, Inc.|National Comprehensive Cancer Network
Sex: MALE
Age: ADULT, OLDER_ADULT
Enrollment: 33
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2028-08-31
Locations: Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States|Brigham and Women's Hospital, Boston, Massachusetts, 02215, United States|Dana-Farber Cancer Institute, Boston, Massachusetts, 02215, United States

Summary:
This research study is being done to determine the rate of testosterone recovery after completing two years of treatment with the combination of relugolix and darolutamide as well as to assess the safety of the drugs when administered in combination.

The names of the drugs in this study are:

* Relugolix (a type of gonadotropin-releasing hormone receptor antagonist)
* Darolutamide (a type of androgen receptor antagonist)

Primary Outcome Measures: 18-month Rate of Testosterone Recovery, Rate of testosterone recovery (TR) defined as the proportion of participants achieving testosterone ≥ lower limit of normal by 18 months after completion of study treatment. Participants who withdrew from trial therapy (due to early progression, toxicity, patient/physician decision or death) before completing 2 years of treatment will be excluded from the analysis. Participants who require resumption of androgen deprivation, withdraw, are lost to follow-up, or die before 18 months of post-treatment follow up has been completed without having achieved testosterone recovery ≥ lower limit of normal beforehand will be included in the analysis and will be considered to be non-recovered., 42 months (18 months after completion of 2 years of treatment)|Grade 3-5 Treatment-related Toxicity Rate, All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definitely related to study treatment based on Common Terminology Criteria for Adverse Events (CTCAE) version 5 are counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation., 24 months. AE collected on day 1 of each cycle (up to 26 cycles in total, each cycle is 28 days)
Secondary Outcome Measures: Geometric Mean Ratio of Single-dose Cmax (highest concentration of drug) and Steady-state Ctrough (the concentration of drug in the blood immediately before the next dose is administered), Geometric mean ratio (GMR) of single-dose Cmax (Cohort 1) and steady-state Ctrough (Cohort 2) of darolutamide and relugolix calculated as the geometric mean when administered in combination with the other agent divided by geometric mean when administered as monotherapy (historical control)., 29 days. Pharmacokinetic (PK) collection prior to the first dose of both drugs and then after 2 hours, 4 hours and 8 hours (Cohort 1) or after 24 hours, 7 days, and 28 days (Cohort 2) of uninterrupted dosing during cycle 1 (each cycle is 28 days).|Rate of Treatment Discontinuation, Rate of treatment discontinuation defined as the proportion of participants who discontinued treatment due to 1) adverse events, 2) disease progression, and 3) participant withdrawal., 24 months. Treatment planned on day 1 of each cycle (up to 26 cycles in total, each cycle is 28 days)|Mean Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score, The FACT-P is a well-established, 39-item questionnaire that was developed and validated specifically in participants with advanced prostate cancer. The FACT-P total score ranges from 0 to 156. Higher values of the FACT-P total and all subscales indicate a higher quality of life., 42 months. Collected at Cycle 1 day 1 (each cycle is 28 days), end of treatment (24 months), and end of study at 18 months after completion of treatment (42 months)