A Study To Evaluate Hypofractionated Proton Therapy Or IMRT For Recurrent, Oligometastatic Prostate Cancer

Radiotherapy With Hypofractionated Abdomino-Pelvic Salvage for Oligonodal Disease Study (RHAPSODY): MC1851 A Randomized, Parallel Phase II Trial Utilizing Proton Therapy or IMRT

This phase II trial studies the side effects of radiation therapy [hypofractionated proton beam radiation therapy (PBRT) or intensity-modulated radiation therapy (IMRT)] for the treatment of prostate cancer that has come back (recurrent) or that has spread to a limited number of sites (oligometastatic) following primary localized treatment. Hypofractionated PBRT delivers smaller doses of radiation therapy over time and may kill more tumor cells and have fewer side effects. IMRT uses high energy x-rays to kill tumor cells and shrink tumors. This trial is being done to find out if a shorter course of radiation therapy is better with fewer side effects for patients with recurrent prostate cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Adenocarcinoma; Stage IV Prostate Cancer AJCC v8; Recurrent Prostate Carcinoma; Metastatic Prostate Adenocarcinoma; Oligometastatic Prostate Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Computed Tomography; Radiation: Proton Beam Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To assess late >= grade 3 gastrointestinal (GI) and/or genitourinary (GU) toxicity of interest within each treatment arm, moderate hypofractionation (MHF) and conventional fractionation (CF), delivered with PBRT or IMRT (late defined as 3 to 24 months after protocol radiation therapy [RT]).

SECONDARY OBJECTIVES:

I. Late grade >= 2 GI and/or GU toxicities of interest within 24 months after protocol treatment, using Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0.

II. Acute grade >= 3 GI and/or GU toxicities of interest during and within 3 months after the protocol treatment, using CTCAE v4.0.

III. Compare the rates of late >= grade 3 GI and/or GU toxicity between the 2 treatment schedules.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo IMRT or PBRT 5 days a week over 3 weeks. Patients undergo positron emission tomography (PET) scan, computed tomography (CT) scan, magnetic resonance imaging (MRI), and blood sample collection throughout the study.

ARM II: Patients undergo IMRT or PBRT 5 days a week over 5 weeks. Patients undergo PET scan, CT scan, MRI, and blood sample collection throughout the study.

After completion of study, patients are followed up at 3-6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male; age >= 18 years
• Histological confirmation of prostate adenocarcinoma
• Recurrent prostate cancer after prior receipt of primary radiotherapy to the prostate [can also include treatment of seminal vesicles (SVs) and lymph nodes (LNs)] or salvage RT to the prostate fossa (can also include prior pelvic RT)

• Oligometastatic extent of disease

  • Recurrent disease involving lymph nodes as diagnosed with choline positron emission tomography (PET)/computed tomography (CT) or other advanced PET imaging [prostate-specific membrane antigen (PSMA) or flucyclovine]
  • Limited to pelvic and/or retroperitoneal/para-aortic lymph nodes
• Zubrod performance score (PS) =< 1
• Signed informed consent

Exclusion Criteria:

• Bone or visceral metastases present at the time of treatment (consolidative radiotherapy allowed)
• Lymph node metastases beyond the pelvis and/or retroperitoneum
• Contraindications to RT (e.g., uncontrolled inflammatory bowel disease)
• Contraindications to androgen suppression
• Concurrent cytotoxic chemotherapy
• Previous or concurrent malignancy other than non-melanoma skin cancer within 5 years of diagnosis of prostate cancer
• Inability to start the radiation portion of the protocol treatment within 6 months after study enrollment
• Medical or psychiatric conditions that preclude informed decision-making or compliance with the protocol treatment or follow-up

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 I (moderate hypofractionation); Patients undergo photon IMRT or PBRT 5 days a week over 3 weeks. Patients undergo PET scan, CT scan, MRI, and blood sample collection throughout the study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Medical Imaging; Magnetic Resonance / Nuclear Magnetic Resonance; nuclear magnetic resonance imaging; sMRI; Magnetic resonance imaging (procedure); Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Intensity-Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Tomography; tomography; CT SCAN; computerized axial tomography; Computerized axial tomography (procedure); Radiation: Proton Beam Radiation Therapy; Undergo proton beam radiation therapy; Other Names: Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Proton Radiation Therapy; positron emission tomography scan; PBRT; Proton; Proton EBRT; Proton External Beam Radiotherapy; Radiation, Proton Beam; External beam radiation therapy protons (procedure); emission tomography (procedure)
Experimental: Arm II (conventional fractionation); Patients undergo IMRT or PBRT 5 days a week over 5 weeks. Patients undergo PET scan, CT scan, MRI, and blood sample collection throughout the study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Medical Imaging; Magnetic Resonance / Nuclear Magnetic Resonance; nuclear magnetic resonance imaging; sMRI; Magnetic resonance imaging (procedure); Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Intensity-Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Tomography; tomography; CT SCAN; computerized axial tomography; Computerized axial tomography (procedure); Radiation: Proton Beam Radiation Therapy; Undergo proton beam radiation therapy; Other Names: Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Proton Radiation Therapy; positron emission tomography scan; PBRT; Proton; Proton EBRT; Proton External Beam Radiotherapy; Radiation, Proton Beam; External beam radiation therapy protons (procedure); emission tomography (procedure)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of late > grade 3 GI and/or GU toxicity	Assessed by the number of patients who experience a late (≥ 90 days after RT start date) grade 3 or higher gastrointestinal (GI) and/or genitourinary (GU) adverse event (AE) defined as possibly, probably, or definitely related to radiation therapy (RT). Adverse events will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Up to 24 months after RT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute adverse events	Assessed by the number of patients with >= grade 3 GI or GU acute adverse events. Acute AEs are defined as those that occur from day 1, or commencement of RT, through 3 months after the completion of protocol treatment.	Up to 3 months after the completion of RT
Incidence of grade 3 or higher GI or GU adverse events per treatment schedule	Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates of late ≥ grade 3 GI and/or GU toxicity will be compared between the treatment schedules.	Up to 60 months
Incidence of late adverse events	Assessed by the number of ≥ grade 2 GI or GU late adverse events per CTCAE v 4.0 will be recorded. A late AE is defined as an adverse event that occurs any time between 3 months and 2 years after completion of protocol treatment.	Between 3 months and 2 years after completion of proton beam therapy
Incidence of adverse events	Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient.	Up to 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded Prostate Cancer Index Composite short form (EPIC-26) questionnaire	The EPIC-26 questionnaire is a 26-item questionnaire used to assess health-related quality of life (HRQOL). Items are scores on a Likert-type scales such as 0-4 where 0=no problem and 4=big problem. Higher scores indicate better HRQOL.	Baseline, up to 60 months
Disease-free survival	Defined as the time from registration until the time of the first occurrence of biochemical failure, local recurrence, regional recurrence, distant metastases, or death due to any cause	Up to 60 months
Disease-specific survival	Defined as the time from registration until death due to prostate cancer (death attributed to carcinoma of the prostate by the investigator or death due to complications of treatment)	Up to 60 months
Overall survival	Defined as the time from registration until death due to any cause	Up to 60 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Brian J. Davis, M.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2020
• Primary Completion (Actual): November 22, 2025
• Study Completion (Estimated): November 22, 2028

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Physical Phenomena; Inorganic Chemicals; Elements; Chemistry Techniques, Analytical; Spectrum Analysis; Ions; Electrolytes; Electromagnetic Phenomena; Magnetic Phenomena; Radiotherapy; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Gases; Elementary Particles; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Heavy Ion Radiotherapy; Cations, Monovalent; Cations; Hydrogen; Nucleons; Specimen Handling; Magnetic Resonance Spectroscopy; X-Rays; Radiotherapy, Intensity-Modulated; Proton Therapy; Protons
• Other Study ID Numbers: MC1851 (Mayo Clinic in Rochester); 19-000708 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

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