Relugolix in Combination With Radiation Therapy for Treating Patients With High Risk Prostate Cancer

Quantifying Optimal Relugolix Duration With Radiation in High Risk Prostate Cancer (QURE-PC)

This phase II trial evaluates the best duration for relugolix to be given in combination with radiation therapy when treating patients with high risk prostate cancer. Prostate cancer is a hormonal influenced cancer. Part of the usual treatment for patients with prostate cancer is androgen deprivation therapy (ADT). ADT is used to lower the amount of testosterone in the body, because testosterone appears to help prostate cancer grow. Relugolix works to reduce testosterone levels, which may inhibit proliferation of prostate cancer cells. It is approved by the Food and Drug Administration to treat prostate cancer. Adding relugolix to standard radiation therapy might work better and have fewer side effects than prior forms of hormonal therapy, but the optimal duration of relugolix in combination with radiation is not known.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage IV Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Radiation: Brachytherapy; Radiation: External Beam Radiation Therapy; Drug: Relugolix; Procedure: Dual X-ray Absorptiometry; Procedure: Bone Scan; Procedure: PSMA PET Scan

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the biochemical recurrence rate between 12 and 24 months of relugolix in patients with high risk prostate cancer treated with combination external beam radiation and brachytherapy.

SECONDARY OBJECTIVES:

I. To compare the composite quality of life in patient treated with 12 months and 24 months of relugolix as assessed by the Expanded Prostate Composite Index Short Form (EPIC-26) instrument.

II. To compare the treatment related toxicity between 12 months and 24 months of relugolix as assessed by Common Terminology Criteria for Adverse Events version 5.0. (CTCAE v 5.0) criteria.

III. To compare the rate of major adverse cardiovascular events (MACE) in patients treated with 12 and 24 months of relugolix.

IV. To establish the rate of patient compliance using patient reported drug diary.

V. To compare the rate of testosterone recovery after 12 and 24 months of relugolix.

EXPLORATORY OBJECTIVE:

I. To establish Decipher genomic classifier as predictor of cancer control.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive relugolix orally (PO) once daily (QD). Cycles repeat every 3 months for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, computed tomography (CT) or magnetic resonance imaging (MRI) or prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan during screening. Patients also undergo dual x-ray absorptiometry (DEXA) scan and may optionally undergo blood sample collection throughout the trial.

ARM B: Patients receive relugolix PO QD. Cycles repeat every 3 months for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, CT or MRI or PSMA PET scan during screening. Patients also undergo DEXA scan and may optionally undergo blood sample collection throughout the trial.

After completion of study treatment, patients in Arm A are followed up every 3 months for 12 months and then every 6 months for up to 36 months and patients in Arm B are followed up every 6 months for up 36 months.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
      • Principal Investigator: Xinglei Shen
      • Contact: Xinglei Shen; Phone Number: 913-588-3600; Email: xshen@kumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability of participant or Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Life expectancy > 5 years

• Patient diagnosed with National Comprehensive Cancer Network (NCCN) high risk and very high risk prostate cancer.

  • High risk is defined as:

    • T3a or
    • Grade group 4 or 5 or
    • Prostate-specific antigen (PSA) > 20 ng/mL

  • Very high risk is defined as:

    • T3b to T4 or
    • Primary Gleason pattern 5 or
    • Two or three high-risk features or
    • > 4 cores with grade group 4 or 5
• Eligible for treatment with combination brachytherapy, external beam radiation, and ADT
• Leukocytes >= 1.0 K/UL
• Platelets >= 100 K/UL
• Hemoglobin ≥ 9 g/dL
• Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN)
• Men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed for the duration of study participation and for 2 weeks following completion of relugolix therapy

Exclusion Criteria:

• Simultaneously enrolled in any therapeutic clinical trial
• Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Has a known allergic reaction to any excipient or component contained in the study drug formulation
• Active grade 3 (per the National Cancer Institute [NCI] CTCAE, version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment
• Current androgen deprivation therapy (unless testosterone > 50 ng/dL). Please note prior or concurrent bicalutamide at 50 mg/daily or less is allowed. Prior androgen deprivation therapy is allowed if testosterone has recovered to > 50 ng/dL
• Prolonged echocardiogram corrected QT (QTc) interval > 440 ns
• Prior pelvic therapy that would significantly overlap with radiation treatment fields
• Prior prostatectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (relugolix, brachytherapy, external beam radiation); Patients receive relugolix PO QD. Cycles repeat every 3 months for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, CT or MRI or PSMA PET scan during screening. Patients also undergo DEXA scan and may optionally undergo blood sample collection throughout the trial.	Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic resonance imaging (procedure); Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Brachytherapy; Undergo brachytherapy; Other Names: Brachytherapy, NOS; Internal Radiation; Internal Radiation Brachytherapy; Internal Radiation Therapy; Radiation Brachytherapy; Radiation, Internal; Radiation: External Beam Radiation Therapy; Undergo external beam radiation therapy; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Teleradiotherapy; Teletherapy; Teletherapy Radiation; External Beam Radiotherapy (conventional); Drug: Relugolix; Given PO; Other Names: TAK-385; Orgovyx; N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea; TAK 385; Relumina; Procedure: Dual X-ray Absorptiometry; Undergo DEXA scan; Other Names: DEXA; DXA; BMD scan; bone mineral density scan; DEXA Scan; dual energy x-ray absorptiometric scan; Dual Energy X-ray Absorptiometry; Dual X-Ray Absorptometry; DXA SCAN; DEXA (Bone Density); Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: PSMA PET Scan; Undergo PSMA PET; Other Names: PSMA PET; Prostate-specific Membrane Antigen PET; PSMA-Positron emission tomography
Experimental: Arm B (relugolix, brachytherapy, external beam radiation); Patients receive relugolix PO QD. Cycles repeat every 3 months for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, CT or MRI or PSMA PET scan during screening. Patients also undergo DEXA scan and may optionally undergo blood sample collection throughout the trial.	Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic resonance imaging (procedure); Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Brachytherapy; Undergo brachytherapy; Other Names: Brachytherapy, NOS; Internal Radiation; Internal Radiation Brachytherapy; Internal Radiation Therapy; Radiation Brachytherapy; Radiation, Internal; Radiation: External Beam Radiation Therapy; Undergo external beam radiation therapy; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Teleradiotherapy; Teletherapy; Teletherapy Radiation; External Beam Radiotherapy (conventional); Drug: Relugolix; Given PO; Other Names: TAK-385; Orgovyx; N-(4-(1-((2,6-Difluorophenyl)methyl)-5-((dimethylamino)methyl)-1,2,3,4-tetrahydro-3-(6-methoxy-3-pyridazinyl)-2,4-dioxothieno(2,3-d)pyrimidin-6-yl)phenyl)-N'-methoxyurea; TAK 385; Relumina; Procedure: Dual X-ray Absorptiometry; Undergo DEXA scan; Other Names: DEXA; DXA; BMD scan; bone mineral density scan; DEXA Scan; dual energy x-ray absorptiometric scan; Dual Energy X-ray Absorptiometry; Dual X-Ray Absorptometry; DXA SCAN; DEXA (Bone Density); Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: PSMA PET Scan; Undergo PSMA PET; Other Names: PSMA PET; Prostate-specific Membrane Antigen PET; PSMA-Positron emission tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical recurrence	Will be defined as serum prostate-specific antigen (PSA) level of nadir + 2 ng/mL by blood test.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite quality of Life	Will be assessed by the Expanded Prostate Composite Index Short Form (EPIC-26) and will be compared between the 2 arms in terms of hormonal domain and sexual domain of EPIC-26. An area under the curve (AUC) metric will be utilized to account for the overall quality of life from baseline through 36 months for each patient. A mixed effect model will be employed to construct an estimate of the difference in AUC between Arms A and B, including fixed effects of time, arm, and baseline characteristics (two or three covariates depending on the available sample size). A two-sample t-test with a significance level of 0.05 will be performed.	Up to 5 years
Incidence of adverse events	Will be assessed by Common Terminology Criteria for Adverse Events version 5.0 and will be reported descriptively.	Up to 5 years
Incidence of major adverse cardiovascular events	Will be assessed by medical record review and will be reported descriptively.	Up to 5 years
Participant compliance	Will be assessed by patient study diary.	Up to 2 years
Time to testosterone recovery	Will be assessed by blood tests and the percentage of patients in each arm who achieved baseline level or minimum 280 ng/dL will be reported at 3-month intervals up through 36 months after treatment completion.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Xinglei Shen, University of Kansas

Study record dates

Study Major Dates

• Study Start (Estimated): November 20, 2023
• Primary Completion (Estimated): October 23, 2025
• Study Completion (Estimated): October 23, 2026

Study Registration Dates

• First Submitted: November 3, 2023
• First Submitted That Met QC Criteria: November 3, 2023
• First Posted (Estimated): November 13, 2023

Study Record Updates

• Last Update Posted (Estimated): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Relugolix
• Other Study ID Numbers: STUDY00150674 (Other Identifier: University of Kansas Cancer Center); P30CA168524 (U.S. NIH Grant/Contract); NCI-2023-09079 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No