Radiation Therapy (Hypofractionated Proton Beam Therapy or IMRT) for the Treatment of Recurrent, Oligometastatic Prostate Cancer Following Primary Localized Treatment

A Randomized, Parallel Phase II Trial of Hypofractionated Proton Therapy or IMRT for Recurrent, Oligometastatic Prostate Cancer Involving Only Pelvic and/or Para-Aortic Lymph Nodes Following Primary Localized Treatment

This phase II trial studies the side effects of radiation therapy (hypofractionated proton beam therapy or 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 proton beam radiation therapy 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 with the hypofractionated regimen with proton beam therapy or intensity-modulated radiation therapy (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 the protocol RT, using the 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 RT, using the 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 proton beam radiation therapy 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 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 splenic vessels [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
• Lymph node metastases beyond the pelvis and/or retroperitoneum
• Contraindications to RT (e.g., uncontrolled inflammatory bowel disease)
• Contraindications to androgen suppression
• Concurrent antineoplastic agents (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 (proton beam radiation therapy); Patients undergo proton beam radiation therapy 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; 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 (IMRT); Patients undergo IMRT 5 days a week over 5 weeks. Patients undergo PET scan, CT scan, MRI, and blood sample collection throughout the study.	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who experience a late (>= 90 days after radiation therapy [RT] start date) grade 3 or higher gastrointestinal (GI) and/or genitourinary (GU) adverse event (AE)	Toxicity will be defined as an adverse event possibly, probably, or definitely related to proton beam therapy. The proportion of grade 3 or higher GI or GU toxicities will be estimated by the number of patients with a late grade 3 or higher GI or GU toxicity divided by the total number of evaluable patients. Exact binomial 90% confidence intervals for the toxicity proportion will be calculated.	Up to 24 months after RT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute adverse events	The rate of >= grade 3 GI or GU acute adverse events will be estimated by the number of patients with a >= grade 3 GI or GU acute adverse event divided by the total number of evaluable patients. Exact binomial 90% confidence intervals for the true rate of >= grade 3 GI or GU acute adverse events will be calculated.	Up to 3 months after the completion of RT
Incidence of late adverse events	The rate of >= grade 2 GI or GU late adverse events will be estimated by the number of patients with a >= grade 2 GI or GU late adverse event divided by the total number of evaluable patients. Exact binomial 90% confidence intervals for the true rate of >= grade 2 GI or GU late adverse events will be calculated.	Between 3 months and 2 years after completion of proton beam therapy
Proportion of grade 3 or higher GI or GU adverse events	The difference between the 2 treatment arm proportions will be determined and exact binomial 90% confidence intervals for the difference in grade 3 or higher GI or GU toxicity rates will be calculated.	Up to 60 months
Incidence of adverse events	All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s). The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Acute and late adverse events will be summarized separately.	Up to 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded Prostate Cancer Index Composite short form (EPIC-26) questionnaire	Subdomains for urinary, bowel, and sexual function will be evaluated at each time point and summarized descriptively. Changes across time will be evaluated to assess patient function and quality of life after study treatment.	Up to 60 months
Disease-free survival	The distribution of disease-free survival will be estimated using the method of Kaplan-Meier.	From registration until the time of the first occurrence of biochemical failure, local recurrence, regional recurrence, distant metastases, or death due to any cause, assessed at 2 and 5 years
Disease-specific survival	The distribution of disease-specific survival will be estimated using the method of Kaplan-Meier.	From registration until the date of death due to prostate cancer, assessed up to 2 and 5 years
Overall survival	The distribution of overall survival will be estimated using the method of Kaplan-Meier.	From registration until the death due to any cause, assessed at 2 and 5 years

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 (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

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 (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 26, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Carcinoma; Recurrence; Adenocarcinoma
• Other Study ID Numbers: MC1851 (Other Identifier: Mayo Clinic in Rochester); NCI-2019-07705 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 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