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

NCT05679388 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IRB22-1150
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer; Prostate Cancer Metastatic; Prostate Adenocarcinoma

Keywords

prostate cancer

Outcome Measures

Primary Outcomes (1)

• Testosterone Suppression of Participants as Assessed by Testosterone Levels

  To determine whether the addition of itraconazole and ritonavir to relugolix sustains testosterone suppression as assessed by participant testosterone levels.

  1 month post start of treatment

Secondary Outcomes (3)

• Decrease in Relugolix Levels

  1 month post start of treatment

• Reduction in Prostate-Specific Antigens Levels of Participants After Study Treatment

  1 month post start of treatment

• Rate of Reported Adverse Events Among Participants

  1 month post start of treatment

Study Arms (5)

Study Group 1

EXPERIMENTAL

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

Drug: Relugolix Pill

Study Group 2a

EXPERIMENTAL

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

Drug: Relugolix Pill; Drug: Itraconazole

Study Group 2b

EXPERIMENTAL

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

Drug: Relugolix Pill; Drug: Ritonavir

Study Group 3a

EXPERIMENTAL

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

Drug: Relugolix Pill; Drug: Itraconazole

Study Group 3b

EXPERIMENTAL

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

Drug: Relugolix Pill; Drug: Ritonavir

Interventions

Relugolix Pill DRUG

A medication used to treat prostate cancer. Relugolix comes as a tablet to take by mouth. It is usually taken with or without food once daily.

Study Group 1; Study Group 2a; Study Group 2b; Study Group 3a; Study Group 3b

Ritonavir DRUG

HIV antiviral It can treat HIV infection, which causes AIDS. It does not cure HIV or AIDS, but combinations of drugs may slow the progress of the disease and prolong life.

Study Group 2b; Study Group 3b

Itraconazole DRUG

A drug used to treat fungal infections.

Also known as: Sporanox

Study Group 2a; Study Group 3a

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participants with prostate cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60453, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

relugolix; Ritonavir; Itraconazole

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles; Piperazines

Study Officials

• Walter Stadler

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2022
• First Posted: January 11, 2023
• Study Start: February 13, 2023
• Primary Completion: August 5, 2024
• Study Completion: August 5, 2024
• Last Updated: September 19, 2024

Record last verified: 2023-10

Locations

US (1)