Testing Shorter Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With High Risk Prostate Cancer

Stage IVA Prostate Cancer AJCC v8 Clinical Trial

Official title:

The Phase III 'High Five Trial' Five Fraction Radiation for High-Risk Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05946213
• Other study ID #: NRG-GU013
• Secondary ID: NCI-2023-04142NR
• Status: Recruiting
• Phase: Phase 3
• Start date: November 13, 2023
• Est. completion date: March 31, 2041

Study information

• Verified date: February 2024
• Source: NRG Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial compares stereotactic body radiation therapy (SBRT), (five treatments over two weeks using a higher dose per treatment) to usual radiation therapy (20 to 45 treatments over 4 to 9 weeks) for the treatment of high-risk prostate cancer. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period of time. This trial is evaluating if shorter duration radiation prevents cancer from coming back as well as the usual radiation treatment.

Description:

PRIMARY OBJECTIVE:

I. To compare metastasis-free survival, determined using conventional imaging, between men with high-risk prostate cancer randomized to ultrahypofractionation (stereotactic body radiation therapy [SBRT]) to those randomized to moderate hypofractionation and conventional fractionation.

SECONDARY OBJECTIVES:

I. To compare physician-reported toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 between treatment arms.

II. To determine if ultrahypofractionation is non-inferior to moderate hypofractionation and conventional fractionation with respect to patient-reported urinary function (assessed by Expanded Prostate Cancer Index Composite [EPIC]-26 urinary domains).

III. To determine if ultrahypofractionation is non-inferior to moderate hypofractionation and conventional fractionation with respect to patient-reported bowel function (assessed by EPIC-26 bowel domain).

IV. To compare patient-reported fatigue (assessed by Patient Reported Outcomes Measurement Information System [PROMIS]-Fatigue) between treatment arms.

V. To compare patient-reported treatment burden (assessed by COmprehensive Score for financial Toxicity [COST]) between treatment arms.

VI. To compare failure-free survival between treatment arms. VII. To compare metastasis-free survival based on molecular imaging between treatment arms.

VIII. To compare overall survival between treatment arms.

EXPLORATORY OBJECTIVES:

I. To compare patient-reported sexual function (assessed by EPIC-26 sexual domain) between treatment arms.

II. To compare patient-reported quality of life (assessed by European Quality of Life Five Dimension Five Level Scale Questionnaire [EQ-5D-5L]) between treatment arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo SBRT for a total of 5 treatments over 2 weeks.

ARM II: Patients undergo external beam radiation treatment (EBRT) for 20-45 treatments over 4 to 9 weeks.

Patients are followed up every 6 months for 5 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1209
• Est. completion date: March 31, 2041
• Est. primary completion date: March 31, 2036
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of prostate cancer

• High-risk disease defined as having at least one or more of the following:

• cT3a-T3b by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.]) Note: cT4 by imaging or on digital rectal exam is not allowed

• The patient's prostate specific antigen (PSA) > 20 ng/mL prior to starting ADT Note: Patients taking a 5-alpha reductase inhibitor (ex finasteride or dutasteride) are eligible. The baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors

• Gleason Score of 8-10

• Pelvic node positive by conventional imaging with a short axis of at least 1.0 cm

• Prostate gland volume less than 100 cc prior to initiation of ADT as reported at time of biopsy or by separate measure with ultrasound or other imaging modalities including MRI or computed tomography (CT) scan

• No definitive clinical or radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e. bone scan, CT scan, MRI); Negative prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is an acceptable substitute

• Age >= 18

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• No prior radical prostatectomy

• Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone releasing hormone [LHRH] agonist and oral anti-androgen) is =< 185 days prior to registration

• Patients enrolled in NRG-GU009 must be enrolled in NRG-GU013 prior to radiation therapy treatment planning and start of radiation therapy

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Stage III Prostate Cancer AJCC v8
• Stage IVA Prostate Cancer AJCC v8

Intervention

Radiation:
• External Beam Radiation Therapy
Undergo EBRT
• Stereotactic Body Radiation Therapy
Undergo SBRT

Locations

Country	Name	City	State
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Aultman Health Foundation	Canton	Ohio
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Kaiser Permanente Dublin	Dublin	California
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Fresno Cancer Center	Fresno	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Jupiter Medical Center	Jupiter	Florida
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Kaiser Permanente- Marshall Medical Offices	Redwood City	California
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Kaiser Permanente-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Memorial Hospital East	Shiloh	Illinois
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Memorial Medical Center	Springfield	Illinois
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Westchester Medical Center	Valhalla	New York
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Reading Hospital	West Reading	Pennsylvania
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
NRG Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient-reported outcomes	The EPIC-26 sexual domain will be assessed as an exploratory endpoint. Each response is standardized to a 0 to 100 scale, with higher scores indicating better health-related quality of life.	Up to 5 years
Primary	Metastasis-Free Survival (MFS)	Based on conventional imaging. MFS will be estimated using the Kaplan-Meier method (Kaplan 1958). A confidence interval approach will be used adjusting for stratification factors. If the one sided 95% upper confidence limit of HR < 1.35, then the null hypothesis of inferiority will be rejected. If the 95% upper confidence limit excludes HR=1.35, then the null hypothesis of inferiority will be rejected. Cox proportional hazards models will be used to obtain unadjusted and adjusted HRs and 95% confidence intervals for the treatment effects.	From randomization to the date of distant metastasis, or death from any cause, assessed up to 15 years
Secondary	Failure-Free Survival	Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test. Cox proportional hazards models will be used to determine hazard ratios and to assess the effects of stratification factors and other covariates of interest, such as age, race, antiandrogen therapy (ADT) adherence, T stage, Gleason score, and performance status on outcomes.	From randomization to the date of distant metastasis, or death from any cause, assessed up to 15 years
Secondary	Overall Survival	Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test. Cox proportional hazards models will be used to determine hazard ratios and to assess the effects of stratification factors and other covariates of interest, such as age, race, ADT adherence, T stage, Gleason score, and performance status on outcomes.	From the date of randomization to the date of death or last known follow-up date, with patients alive at the last known follow-up time treated as censored, assessed up to 15 years
Secondary	MFS	Based on molecular imaging. Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test. Cox proportional hazards models will be used to determine hazard ratios and to assess the effects of stratification factors and other covariates of interest, such as age, race, ADT adherence, T stage, Gleason score, and performance status on outcomes.	From randomization to the date of distant metastasis, or death from any cause, assessed up to 15 years
Secondary	Incidence of Adverse Events (AEs)	AEs will be graded using National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5. Counts of all AEs by grade will be provided by treatment arm.	Up to 15 years
Secondary	Urinary Incontinence domain of the Expanded Prostate Cancer Index Composite (EPIC-26)	Each response is standardized to a 0 to 100 scale, with higher scores indicating better health-related quality of life.	Up to 5 years
Secondary	Urinary Irritative/Obstructive domain of the Expanded Prostate Cancer Index Composite (EPIC-26)	Each response is standardized to a 0 to 100 scale, with higher scores indicating better health-related quality of life.	Up to 5 years
Secondary	Bowel domain of the Expanded Prostate Cancer Index Composite (EPIC-26)	Each response is standardized to a 0 to 100 scale, with higher scores indicating better health-related quality of life.	Up to 5 years
Secondary	Fatigue	Measured by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue. Raw scores range from 7 to 35 and are standardized. A higher score indicates more fatigue.	Up to 5 years
Secondary	Cost	Measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-COST.	Up to 1 year