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Patients undergo RT using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity.

Patients undergo RT as Arm I. Patients also receive ADT consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days.

Patients receive RT and ADT as in Arm II. Patients also receive darolutamide PO BID on days 1-90. Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Darolutamide

Degarelix

Histrelin

Radiation Therapy

Triptorelin

Site Public Contact

Andrew M. McDonald

Yerko O. Borghero

Sanjay Maraboyina

Christopher U. Jones

Luis Mariscal

Zachary S. Zumsteg

Garth A. Green

Samantha A. Seaward

Jes Alexander

Lloyd T. Miyawaki

Richard L. Jennelle

Richard K. Valicenti

Nitya Alluri

Robert B. Ash

Julian C. Hong

Justin C. Voog

Tyler Robin

Nicholas DiBella

Erin Schwab

Randall Brenneman

Christopher M. Iannuzzi

Philip Gilbo

Gregory A. Masters

Brian H. Ramnaraign

Frank A. Vicini

Michael A. Weller

Sagar A. Patel

Adnan Elhammali

John A. Pablo

Bryan A. Faller

Sean Sachdev

Dian Wang

Matthew Koshy

Priyank P. Patel

Matthew Siegel

Neil B Desai, MD

Alejandro Berlin, MD

This phase III trial uses the Decipher risk score to guide intensification (for higher Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better match therapies to an individual patient's cancer aggressiveness. The Decipher risk score evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk scores, this trial compares radiation therapy alone to the usual treatment of radiation therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation therapy blocks the production or interferes with the action of male sex hormones such as testosterone, which plays a role in prostate cancer development. Giving radiation treatment alone may be the same as the usual approach in controlling the cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy. In patients with higher Decipher gene risk, this trial compares the addition of darolutamide to usual treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading.

PRIMARY OBJECTIVES:

I. To determine whether men with National Comprehensive Cancer Network (NCCN) unfavorable intermediate risk (UIR) prostate cancer and lower Decipher genomic risk (Decipher score \< 0.40) treated with radiation therapy (RT) alone instead of 6 months androgen deprivation therapy (ADT) + RT experience non-inferior rate of distant metastasis. (De-intensification study) II. To determine whether men with NCCN UIR prostate cancer who are in the higher genomic risk (Decipher score \>= 0.40) will have a superior metastasis-free survival through treatment intensification with darolutamide added to the standard of RT plus 6 months ADT. (Intensification study)

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

II. To compare time to prostate specific antigen (PSA) failure between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

III. To compare metastasis free survival (MFS) based on conventional imaging between the standard of care (RT plus 6 months of ADT) and de-intensification intervention (RT alone).

IV. To compare MFS based on either conventional and/or molecular imaging between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

V. To compare cumulative incidence of locoregional failure based upon conventional imaging and/ or biopsy between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months ADT plus darolutamide) interventions.

VI. To compare cumulative incidence of distant metastasis based upon conventional imaging between standard of care (RT plus 6 months of ADT) and intensification intervention (RT plus 6 months ADT plus darolutamide).

VII. To compare cumulative incidence of distant metastasis based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

VIII. To compare prostate cancer-specific mortality between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

IX. To compare sexual and hormonal related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

X. To compare fatigue, as measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

XI. To compare cognition, as measured by the Functional Assessment of Chronic Illness Therapy-Cognitive (FACT-Cog) perceived cognitive abilities subscale, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

EXPLORATORY OBJECTIVES:

I. To compare changes in cardio-metabolic markers, including body mass index, lipids, blood glucose, complete blood count (CBC), comprehensive metabolic panel (CMP), and hemoglobin (Hgb) A1c, between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

II. To compare PSA failure-free survival with non-castrate testosterone and no additional therapies between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

III. To compare cumulative incidence of locoregional failure based upon either conventional and/or molecular imaging between standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

IV. To compare castrate-resistant prostate cancer (CRPC) between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

V. To compare bowel and urinary function related quality of life, as measured by the Expanded Prostate Cancer Index Composite-26 (EPIC), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

VI. To compare time to testosterone recovery (defined as a T \> 200ng/dL) between the standard of care (RT plus 6 months of ADT) and intensification (RT plus 6 months of ADT plus darolutamide) interventions.

VII. To compare health utilities, as measured by the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L), between the standard of care (RT plus 6 months of ADT) and either the de-intensification (RT alone) or intensification (RT plus 6 months of ADT plus darolutamide) interventions.

VIII. To develop and assess a machine learning/artificial intelligence algorithm for radiotherapy planning and/or quality assurance.

IX. To perform future translational correlative studies using biological data, Decipher results, and clinical outcomes.

OUTLINE:

DE-INTENSIFICATION STUDY: Patients with Decipher score \< 0.40 are randomized to 1 of 2 arms.

ARM I: Patients undergo RT using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo RT as Arm I. Patients also receive ADT consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days.

INTENSIFICATION STUDY: Patients with Decipher score \>= 0.40 are randomized to 1 of 2 arms.

ARM III: Patients receive treatment as in Arm II.

ARM IV: Patients receive RT and ADT as in Arm II. Patients also receive darolutamide orally (PO) twice daily (BID). Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 12, 24, 36, 48 and 60 months.

Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score

Parallel Phase III Randomized Trials of Genomic-Risk Stratified Unfavorable Intermediate Risk Prostate Cancer: De-Intensification and Intensification Clinical Trial Evaluation (GUIDANCE)

CRPC is defined as PSA increase \> 25% and more than 2 ng/mL above nadir on study in conjunction with a serum testosterone (T) \< 50 ng/mL, confirmed by repeat measurements at least 2 weeks apart. Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.

Measured EPIC-26. Mixed effect regression models will be fit to compare the changes over time in the domain scores. Covariates will include treatment, time, and treatment-by-time treatment interaction terms.

Will include body mass index, lipids, blood glucose, complete blood count, comprehensive metabolic panel, and hemoglobin A1c. Mixed effect regression models will be fit to compare the changes over time in the cardio-metabolic markers between treatment groups. Covariates will include treatment, time, and treatment-by-time treatment interaction terms.

Measured by the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L). ). The bootstrap (Efron 1980) will be performed to obtain standard errors, test for significant differences, and generate 95% confidence intervals.

Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk. Changes in quality of life measures will be correlated with changes in testosterone levels.

Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.

MFS will be estimated by the Kaplan-Meier (1958) method and compared between the two treatment arms using a stratified log-rank test (stratified by the randomization stratification factors) at one-sided alpha level of 0.025.

Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified log-rank test. Cox regression models will also be fit, adjusted for the stratification factors, to estimate hazard ratios, together with 95% confidence intervals.

Defined as PSA \> 2 ng/ml above the nadir post randomization. Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.

Will be estimated by the Kaplan-Meier method and compared between treatments arms by stratified log-rank test.

Will compare cumulative incidence between arms.

Will be analyzed using competing-risk methods (Gooley 1999) where, in each case death from causes other than prostate cancer as the competing risk.

Measured by the Expanded Prostate Cancer Index Composite-26 (EPIC-26).

Measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue instrument.

Measured by the Functional Assessment of Chronic illness Therapy-Cognitive (FACT-Cog).

Defined as defined as recurrence within the pelvis including lymph nodes below the iliac bifurcation, or prostate. Will be analyzed using competing-risk methods (Gooley 1999) where, in each case, death prior to occurrence of the event in question will be a competing risk.

National Cancer Institute (NCI)

NRG Oncology

Symptoms and General Pathology

Immune System Diseases

Rare Diseases

Recurrence

Hypersensitivity

Disease Attributes

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Kennedy Disease

Anti-Inflammatory Agents

Prednisone

Cortisone

Glucocorticoids

Patients undergo SBRT and receive ARPI (abiraterone and prednisone, apalutamide, darolutamide, or enzalutamide) and ADT (leuprolide, triptorelin, histrelin, goserelin, degarelix, or relugolix). Cycles repeat every 4 months (16 weeks) for up to 6 months in the absence of unacceptable toxicity. Patients then undergo watchful waiting thereafter until disease progression.

Patients undergo SBRT with watchful waiting. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity.

Abiraterone

Apalutamide

Biospecimen Collection

Bone Scan

Computed Tomography

Enzalutamide

Magnetic Resonance Imaging

Patient Observation

Positron Emission Tomography

Questionnaire Administration

Stereotactic Body Radiation Therapy

Clinical Trials Referral Office

Jacob J. Orme, M.D., Ph.D.

This phase II trial studies the effects of stereotactic body radiation therapy (SBRT) and the timing of treatment with androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT) in treating patients with hormone sensitive prostate cancer that has spread from where it first started to other places in the body (metastatic), and that has come back after a period of improvement (recurrent). SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Androgen can cause the growth of prostate cells. ADT lowers the amount of androgen made by the body. This may help stop the growth of tumor cells that need androgen to grow. Androgen receptor pathway inhibitors work by blocking the effects of androgen to stop the growth and spread of tumor cells. Giving SBRT alone with watchful waiting may be as effective in treating prostate cancer as giving SBRT together with ARPI and ADT.

PRIMARY OBJECTIVES:

I. To evaluate and compare modified radiographic progression-free survival (mrPFS) in patients with metachronous recurrent oligometastatic prostate cancer treated with SBRT and 6 months ADT/ARPI followed by watchful wait (Group A) versus SBRT followed by watchful wait (Group B).

SECONDARY OBJECTIVES:

I. To evaluate and compare overall survival (OS) between two treatment groups. II. To evaluate and compare biochemical progression-free survival (bPFS) between two treatment groups.

III. To evaluate and compare time to local progression between two treatment groups.

IV. To evaluate and compare time to distant progression between two treatment groups.

V. To evaluate the toxicity profile of 6 months of ADT/ARPI as assessed per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

TERTIARY OBJECTIVES:

I. To evaluate and compare castration-resistant prostate cancer (CRPC)-free survival between two treatment groups NOTE: CRPC-free survival: radiographic progression-free survival with castrate-level testosterone (\< 50ng/mL).

II. Determine the efficacy of extracellular vesicles (EVs) as a minimal residual disease (MRD) marker.

III. Determine the efficacy of EVs as an early indicator of disease relapse. IV. Characterize duration of response. V. Determine whether early ADT and ARPI hasten CRPC. VI. Determine how circulating tumor deoxyribonucleic acid (ctDNA) compares as a biomarker to EVs.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP A: Patients undergo SBRT and receive ARPI (abiraterone and prednisone, apalutamide, darolutamide, or enzalutamide) and ADT (leuprolide, triptorelin, histrelin, goserelin, degarelix, or relugolix). Cycles repeat every 4 months (16 weeks) for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients then undergo watchful waiting thereafter until disease progression.

GROUP B: Patients undergo SBRT with watchful waiting. Cycles repeat every 4 months (16 weeks) in the absence of disease progression or unacceptable toxicity.

Additionally, patients undergo blood sample collection and positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), or bone scan.

Upon completion of study interventions patients are followed up every 6 months for up to 5 years.

Stereotactic Body Radiation Therapy Plus Androgen Receptor Pathway Inhibitor and Androgen Deprivation Therapy for Treatment of Metastatic, Recurrent Hormone-Sensitive Prostate Cancer, DIVINE Trial

Dynamic Investigator Initiated Enterprise (DIVINE) in Prostate Cancer

Modified radiographic progression-free survival (mrPFS) is defined as the time from the date of randomization (enrollment to study) to the date of the first occurrence of either death due to any cause or radiographic progression per prostate cancer working group 3 criteria, which are not addressable by stereotactic body radiation therapy (SBRT). Radiographic progression not addressable by SBRT includes 1) soft tissue lesions measured by response evaluation criteria in solid tumors (RECIST) v1.1 or 2) bone lesions evaluated only on bone scans per 2+2 rule (2 new lesions on the 1st post-treatment scan plus 2 additional new lesions on the subsequent scan with persistence or 2 new lesions compared to 1st post-treatment scan persisting on the follow-up scan). Date of progression is the first scan showing lesions. Radiographic progression disease that can be addressed by SBRT will not be an mrPFS event.

Defined as time from the date of randomization (enrolled to study) to the date of death due to any cause.

Defined as time from the date of randomization (enrollment to study) to the date of death due to any cause or biologic progressive disease, whichever occurs first.

Defined as time from date of randomization (enrollment to study) to the date of the first documented local progression. Local progression includes growth of any existing lesion by 20% or more that persists on a subsequent scan (modified from RECIST 1.1), whether or not these lesions are or can be addressed by radiotherapy.

Defined as time from date of randomization (enrollment to study) to the date of the first documented distant progression. Distant progression includes new lesions on imaging, whether or not these lesions are or can be addressed by radiotherapy.

Defined as the proportion of patients experienced at least one Grade 3, Grade 4, or Grade 5 of any type of AE during the protocol defined treatment. AEs will be assessed using common terminology criteria for adverse events (CTCAE) v5.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score	NCT05050084	Prostate Adenoc...	Bicalutamide Buserelin Darolutamide Degarelix Flutamide Goserelin Histrelin Leuprolide Radiation Thera... Relugolix Triptorelin	18 Years -	NRG Oncology
Stereotactic Body Radiation Therapy Plus Androgen Receptor Pathway Inhibitor and Androgen Deprivation Therapy for Treatment of Metastatic, Recurrent Hormone-Sensitive Prostate Cancer, DIVINE Trial	NCT06378866	Recurrent Castr... Stage IVB Prost... Recurrent Prost... Castration-resi...	Abiraterone Apalutamide Biospecimen Col... Bone Scan Computed Tomogr... Darolutamide Degarelix Enzalutamide Goserelin Histrelin Leuprolide Magnetic Resona... Patient Observa... Positron Emissi... Prednisone Questionnaire A... Relugolix Stereotactic Bo... Triptorelin	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for histrelin

Every month we try and update this database with for histrelin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for histrelin

Every month we try and update this database with for histrelin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for histrelin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.