A Study of Extending Relugolix Dosing Intervals Through Addition of Itraconazole or Ritonavir in Prostate Cancer Patients

The University of Chicago

Status and phase: Terminated; Phase 1

Conditions: Prostate Adenocarcinoma; Prostate Cancer Metastatic; Prostate Cancer

Treatments: Drug: Itraconazole; Drug: Relugolix Pill; Drug: Ritonavir

Study type: Interventional

Funder types: Other

Identifiers

NCT05679388

IRB22-1150

Details and patient eligibility

About

Researchers leading this study hope to learn about the safety of combining the study drug relugolix with another study drug called itraconazole or ritonavir in prostate cancer. This study is for individuals who have advanced prostate cancer and plans to have medical castration (the use of medications or chemicals to lower hormone production in the testicles). Your participation in this research will last up to 1 month.

The purpose of this research is to gather information on the safety and effectiveness of relugolix in combination with ritonavir or itraconazole. The goal of this research is to find out if combining two medications (relugolix and itraconazole or relugolix and ritonavir) could possibly lead to using less relugolix, which is an expensive drug.

Enrollment: 60 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must have histologically or cytologically confirmed prostate cancer with plans to start medical castration therapy.
• Age 18 or older. Because no dosing or adverse event data are currently available on the use of relugolix in combination with itraconazole or ritonavir in patients <18 years of age, children are excluded from this study.
• Eastern Cooperative Oncology Group performance status ≤2 (Karnofsky ≥60%)
• Participants must satisfy the following laboratory criteria:
• Testosterone > 200 ng/dl
• QTc within normal limits
• Aspartate Transferase (AST)/alanine transaminase (ALT) < 3x upper limit of normal
• Ability to take oral medication and be willing to adhere to the medication regimen.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• Need for combination systemic therapy for prostate cancer including docetaxel and/or second-generation androgen receptor pathway targeted agents (i.e. abiraterone, enzalutamide, apalutamide, darolutamide, etc).
• Concurrent therapy with strong interacting drugs with CYP3A4 and P-gp (See Appendix list of strong inhibitors or inducers) due to concerning possible drug-drug interactions with itraconazole, ritonavir and relugolix. Potential drug-drug interactions will also be reviewed by study investigators prior to enrollment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to relugolix, itraconazole or ritonavir.
• Patients receiving treatment with another investigational drug or other intervention within 3 expected half-lives of the agent.
• Serious or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• New York Heart Association Class III of IV congestive heart failure
• Known gastrointestinal malabsorption.
• Active psychiatric illness/social situations that would limit compliance with protocol requirements.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 5 patient groups

Study Group 1

Experimental group

Description:

All study participants will receive a starting dose of relugolix (360 mg in the form of three 120 mg tablets) on Day 1 of the 29-day drug administration period. After Day 1, you will receive relugolix on its own or relugolix combined with another medication called itraconazole or ritonavir. The combination of medications you receive, the dosage for each medication, and when you take each medication will be based on the study group you are enrolled in. Study Group 1 will receive: * Relugolix (360 mg) on Day 1 * Relugolix (120 mg) on Days 2-7

Treatment:

Drug: Relugolix Pill

Study Group 2a

Experimental group

Description:

All study participants will receive a starting dose of relugolix (360 mg in the form of three 120 mg tablets) on Day 1 of the 29-day drug administration period. After Day 1, you will receive relugolix on its own or relugolix combined with another medication called itraconazole or ritonavir. The combination of medications you receive, the dosage for each medication, and when you take each medication will be based on the study group you are enrolled in. Study Group 2a will receive: * Relugolix (360 mg) on Day 1 * Relugolix (120 mg) on Days 2-7 * Itraconazole (200 mg) on Days 1-14

Treatment:

Drug: Relugolix Pill

Drug: Itraconazole

Study Group 2b

Experimental group

Description:

All study participants will receive a starting dose of relugolix (360 mg in the form of three 120 mg tablets) on Day 1 of the 29-day drug administration period. After Day 1, you will receive relugolix on its own or relugolix combined with another medication called itraconazole or ritonavir. The combination of medications you receive, the dosage for each medication, and when you take each medication will be based on the study group you are enrolled in. Study Group 2b will receive: * Relugolix (360 mg) on Day 1 * Relugolix (120 mg) on Days 2-7 * Ritonavir (100 mg tablets taken by mouth) on Days 1-14

Treatment:

Drug: Ritonavir

Drug: Relugolix Pill

Study Group 3a

Experimental group

Description:

All study participants will receive a starting dose of relugolix (360 mg in the form of three 120 mg tablets) on Day 1 of the 29-day drug administration period. After Day 1, you will receive relugolix on its own or relugolix combined with another medication called itraconazole or ritonavir. The combination of medications you receive, the dosage for each medication, and when you take each medication will be based on the study group you are enrolled in. Study Group 3a will receive: * Relugolix (360 mg) on Day 1 * Relugolix (120 mg) on Days 2-4 * Itraconazole (200 mg tablets taken by mouth) on Days 1-14

Treatment:

Drug: Relugolix Pill

Drug: Itraconazole

Study Group 3b

Experimental group

Description:

All study participants will receive a starting dose of relugolix (360 mg in the form of three 120 mg tablets) on Day 1 of the 29-day drug administration period. After Day 1, you will receive relugolix on its own or relugolix combined with another medication called itraconazole or ritonavir. The combination of medications you receive, the dosage for each medication, and when you take each medication will be based on the study group you are enrolled in. Study Group 3b will receive: * Relugolix (360 mg) on Day 1 * Relugolix (120 mg) on Days 2-4 * Ritonavir (100 mg) on Days 1-14

Treatment:

Drug: Ritonavir

Drug: Relugolix Pill