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Trial record 1 of 1 for:    NRG-GU011
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Testing the Addition of the Drug Relugolix to the Usual Radiation Therapy for Advanced-Stage Prostate Cancer (NRG PROMETHEAN)

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ClinicalTrials.gov Identifier: NCT05053152
Recruitment Status : Recruiting
First Posted : September 22, 2021
Last Update Posted : August 15, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Brief Summary:
This phase II trial tests whether relugolix and radiation therapy works to shrink tumors in patients with prostate cancer that has spread in a limited way to 1 to 5 other parts of the body (oligometastatic). Testosterone can cause the growth of prostate cancer cells. Relugolix lowers the amount of testosterone made by the body. This may help stop the growth of tumor cells that need testosterone to grow. Giving relugolix with radiation therapy may help lower the chance of prostate cancer growing or spreading.

Condition or disease Intervention/treatment Phase
Oligometastatic Prostate Carcinoma Prostate Adenocarcinoma Stage IVB Prostate Cancer AJCC v8 Drug: Placebo Administration Other: Quality-of-Life Assessment Drug: Relugolix Radiation: Stereotactic Body Radiation Therapy Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. Compare conventional radiological progression-free survival (rPFS) for positron emission tomography (PET)-detected, biochemically recurrent, oligometastatic, castration-sensitive prostate cancer patients treated with stereotactic ablative body radiation therapy (SABR) plus placebo versus (vs.) SABR plus relugolix.

SECONDARY OBJECTIVES:

I. Compare conventional or PET-based radiological progression-free survival (prPFS) between treatment arms.

II. Compare patient-reported sexual and hormonal quality of life as assessed by corresponding Expanded Prostate Cancer Index Composite Short Form (EPIC-26) domains between treatment arms.

III. Compare other measures of quality of life obtained from the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ5D-5L), European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue instruments between the two treatment arms.

IV. Compare time to salvage therapy and time to castration-resistance between treatment arms.

V. Compare local progression (SABR-targeted lesion), biochemical progression, distant metastases, prostate cancer-specific mortality, metastasis-free survival, and overall survival between treatment arms.

VI. Determine adverse events rates and compare rates between the two treatment arms.

EXPLORATORY OBJECTIVE:

I. Evaluate genomic and peripheral tissue and blood markers of treatment response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive placebo orally (PO) once daily (QD) on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3 and 6 months, every 6 months for 4 years, and then annually thereafter.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 269 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Double-Blinded, Placebo-Controlled Trial of PROstate OligoMETastatic RadiotHErapy With or Without ANdrogen Deprivation Therapy in Oligometastatic Prostate Cancer (NRG Promethean)
Actual Study Start Date : December 8, 2021
Estimated Primary Completion Date : October 10, 2024
Estimated Study Completion Date : October 10, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Relugolix

Arm Intervention/treatment
Placebo Comparator: Arm I (placebo, SABR)
Patients receive placebo PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Placebo Administration
Given PO

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Radiation: Stereotactic Body Radiation Therapy
Undergo SABR
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy

Experimental: Arm II (relugolix, SABR)
Patients receive relugolix PO QD on days 1-180 and undergo SABR for 1-3 weeks in the absence of disease progression or unacceptable toxicity.
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Drug: Relugolix
Given PO
Other Names:
  • 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
  • Orgovyx
  • TAK 385
  • TAK-385

Radiation: Stereotactic Body Radiation Therapy
Undergo SABR
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy




Primary Outcome Measures :
  1. Radiological progression-free survival (rPFS) [ Time Frame: Time from randomization to the occurrence of radiological progression detected by conventional imaging or death from any cause, assessed up to 5 years ]
    The rPFS curves will be estimated by the Kaplan-Meier method and compared between the two treatment arms using a one-sided, logrank test stratified by the three randomization factors.


Secondary Outcome Measures :
  1. Positron emission tomography (PET)-based radiological progression-free survival [ Time Frame: Time from randomization to the occurrence of conventional or PET-based radiological progression or death from any cause, assessed up to 5 years ]
    Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.

  2. Metastasis-free Survival [ Time Frame: From randomization to distant metastases or death from any cause, assessed up to 5 years ]
    Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.

  3. Overall Survival [ Time Frame: From randomization to death from any cause, assessed up to 5 years ]
    Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified logrank test. Cox regression models will also be fit, adjusted for the stratification factors and other prognostic baseline factors, to estimate hazard ratios, together with 95% confidence intervals.

  4. Sexual Function [ Time Frame: Up to 5 years ]
    Assessed by Expanded Prostate Cancer Index Composite Short Form (EPIC-26).

  5. Fatigue [ Time Frame: Up to 5 years ]
    Assessed by Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue short form.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of prostate adenocarcinoma at any anatomical location (for example, prostate, metastatic site), including intraductal or ductal carcinoma, at any time before registration
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 120 days prior to registration
  • Prior curative-intent treatment to the prostate, by either:

    • External beam and/or brachytherapy to: Prostate alone, prostate and seminal vesicles, prostate and pelvic nodes, or radiation to all three sites
    • Radical prostatectomy alone, radical prostatectomy plus postoperative radiotherapy to the prostate bed, or radical prostatectomy plus postoperative radiotherapy to the pelvic nodes
  • Must meet study entry criteria based on the following diagnostic workup within 120 days prior to registration:

    • History and physical examination;
    • Technetium TC-99m (99mTc) bone scan (Must be negative);
    • Either computed tomography (CT) or magnetic resonance imaging (MRI) of pelvis +/- abdomen (Must be negative);
    • Fluciclovine or prostate-specific membrane antigen (PSMA) PET scan (Must be positive with exception of local disease);
    • Note: All 3 scans are mandatory (bone scan; CT/magnetic resonance [MR]; PET)
  • 1 - 5 oligometastatic lesions in bone and/or nodal/soft tissue sites on fluciclovine or PSMA PET within 120 days prior to registration and includes at least ONE of the following:

    • Bone - each metastasis is counted (for example, 2 distinct lesions in the right ilium count as 2 oligometastatic lesions)
    • Extrapelvic Nodal/ soft tissue - requires at least one extrapelvic inguinal or a nodal/soft tissue lesion superior to the iliac bifurcation (that is, American Joint Committee on Cancer [AJCC] M1a version 8)
    • Note: Although a patient must have bone and/or extrapelvic disease to be eligible, when counting the number of oligometastatic lesions, each lymph node lesion, whether pelvic or extrapelvic, is counted (for example, 2 distinct lymph nodes in the right external iliac basin count as 2 oligometastatic lesions; one extrapelvic and one pelvic node count as 2 oligometastic lesions, etc)
  • Serum total prostate-specific antigen (PSA) < 10.0 ng/mL obtained within 120 days prior to registration that also meets ONE of the following PSA recurrence definitions:

    • PSA > post-radiation therapy (RT) nadir PSA + 2 ng/mL, if patient received-radiation therapy to intact prostate, or
    • Current PSA > 0.2 ng/mL, with a second confirmatory PSA > 0.2 ng/mL if patient received a radical prostatectomy with or without post-op RT
  • Must have > 3 PSA values within the last two years since end of primary treatment or within the last 2 years prior to registration, whichever is less

    • Note: PSA doubling time must be calculated by entering all PSA values since end of primary treatment or within the last 2 years prior to registration (whichever is less) into the PSA Doubling Time Calculator found at MDCalc.com
  • Serum total testosterone > 100 ng/dL within 120 days prior to registration

    • Note: Prior androgen deprivation therapy (other than bilateral orchiectomy) is allowed if discontinued prior to registration and serum total testosterone is >= 100 ng/dL
  • Total bilirubin: =< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, subject is eligible if direct bilirubin is =< 1.5 x ULN) (within 120 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): =< 2.5 x institutional ULN (within 120 days prior to registration)
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

    • Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

    • Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • The patient must agree to use a highly effective contraception (even men with vasectomies) if he is having sex with a woman of childbearing potential or with a woman who is pregnant while on study drug and for 2 weeks following the last dose of study drug
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

  • Clinical, biopsy-proven, or radiologic (conventional or PET imaging) evidence of local tumor recurrence in the prostate and/or periprostatic/seminal vesicle region after radiotherapy, or in the prostate bed after prostatectomy

    • Note: if a patient had a prior local recurrence and received local salvage therapy, the patient is eligible if there is no current evidence of disease in the prostate/prostate bed. Patients with positive findings on examination or imaging remain eligible if biopsy of the site is negative for cancer
  • Currently on androgen deprivation or anti-androgen therapy
  • 3Definitive radiologic evidence of metastatic disease on conventional imaging, defined by one of the following:

    • Osseous metastasis on 99mTc radionuclide bone scan, or
    • Extra pelvic nodal/soft tissue disease (> 1.5 cm in short axis) on CT or MRI pelvis +/- abdomen
  • Spinal cord compression, or spinal intramedullary, brain, and/or visceral (for example liver, lung, etc.) metastasis

    • Note: Spinal metastases (PET-detected) with epidural extension are eligible if there is > 0.3 cm spatial separation between the gross tumor volume and spinal cord
  • Biopsy-proven prostatic carcinoma with signet-ring, sarcomatoid, or neuroendocrine features (for example, small cell)
  • Prior metastatic or non-metastatic, invasive malignancy (except non metastatic, non-melanomatous skin cancer) unless continuously disease free for >= 3 years
  • Prior chemotherapy for prostate cancer or bilateral orchiectomy

    • Note: Prior chemotherapy for a different cancer is allowed if continuously disease-free for >= 3 years
  • Prior radiotherapy to a lesion (i.e. oligometastatic recurrence by PET)

    • Note: Lesions outside of a previously irradiated planning treatment volume (PTV) are eligible as long as the prescription isovolume dose of any prior radiotherapy course is > 2.0 cm distant from new lesion
  • Inability to treat all oligometastatic sites with radiotherapy in the judgement of the investigator
  • Intrapelvic lymph nodes as only site of prostate cancer recurrence
  • Inability to swallow whole, undivided, unchewed, and uncrushed pills
  • Known gastrointestinal disorder affecting oral medication absorption
  • Co-morbidity defined as follows:

    • Patients with any comorbidities that would prohibit completion of protocol specified therapy
    • Inflammatory bowel disease in patients in whom abdominopelvic radiotherapy is planned
    • History of congenital long QT syndrome
    • Current severe or unstable angina
    • New York Heart Association functional classification III/IV heart failure (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05053152


Locations
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United States, Illinois
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
Contact: Site Public Contact    217-876-4762    morganthaler.jodi@mhsil.com   
Principal Investigator: Bryan A. Faller         
Crossroads Cancer Center Recruiting
Effingham, Illinois, United States, 62401
Contact: Site Public Contact    217-876-4762    morganthaler.jodi@mhsil.com   
Principal Investigator: Bryan A. Faller         
United States, Michigan
GenesisCare USA - Farmington Hills Recruiting
Farmington Hills, Michigan, United States, 48334
Contact: Site Public Contact    941-833-5700    Rudi.Ross@usa.genesiscare.com   
Principal Investigator: Frank A. Vicini         
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Bridget F Koontz NRG Oncology
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Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT05053152    
Other Study ID Numbers: NRG-GU011
NCI-2021-09164 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GU011 ( Other Identifier: NRG Oncology )
NRG-GU011 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: September 22, 2021    Key Record Dates
Last Update Posted: August 15, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Relugolix
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs