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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Metastatic Prostate Adenocarcinoma, Oligometastatic Prostate Carcinoma, Prostate Adenocarcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8

Intervention / Treatment
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* Radiation: Intensity-Modulated Radiation Therapy
* Radiation: Proton Beam Radiation Therapy
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (proton beam radiation therapy)<br>Patients undergo proton beam radiation therapy 5 days a week over 3 weeks. | Radiation: Proton Beam Radiation Therapy<br>* Undergo proton beam radiation therapy<br>* Other names: Radiation, Proton Beam;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (IMRT)<br>Patients undergo IMRT 5 days a week over 5 weeks. | Radiation: Intensity-Modulated Radiation Therapy<br>* Undergo IMRT<br>* Other names: Radiation, Intensity-Modulated Radiotherapy;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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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 |