Proton Radiation Therapy for the Treatment of Patients With High Risk Prostate Cancer

Extended-Field Lymph Node Proton Irradiation for High Risk Prostate Cancer

This phase II trial investigates whether proton radiation therapy directed to the prostate tumor, pelvic, and para-aortic lymph nodes, is an effective way to treat patients with high-risk or lymph node positive prostate cancer who are receiving radiation therapy, and if it will result in fewer gastrointestinal and genitourinary side effects. Proton beam therapy is a new type of radiotherapy that directs multiple beams of protons (positively charged subatomic particles) at the tumor target, where they deposit the bulk of their energy with essentially no residual radiation beyond the tumor. By reducing the exposure of the healthy tissues and organs to radiation in the treatment of prostate cancer, proton therapy has the potential to better spare healthy tissue and reduce the side effects of radiation therapy.

Study Overview

• Status: Recruiting
• Conditions: Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Survey Administration; Radiation: High-Dose Rate Brachytherapy; Radiation: Proton Beam Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the rate of acute grade 2+ gastrointestinal toxicity compared to historical photon treatments.

SECONDARY OBJECTIVES:

I. To determine the rate of acute grade 2+ genitourinary toxicity compared to historical photon treatments.

II. To assess the feasibility of extended-field proton irradiation of high-risk prostate.

III. To demonstrate safety of proton therapy followed by high dose rate (HDR) boost.

IV. To determine patient-reported outcomes (PROs) of toxicity.

OUTLINE:

Patients undergo conventionally fractionated proton beam therapy daily on Monday-Friday. Patients may receive a high-dose rate brachytherapy boost.

After completion of study treatment, patients are followed up at 1, 3, 6, 9 and 12 months, and 1.5, 2, 2.5, and 3 years.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pretesh Patel, MD; Phone Number: 404-778-3473; Email: pretesh.patel@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital/Winship Cancer Institute
      • Contact: Ardith R. DeShay; Phone Number: 404-686-1858; Email: adeshay@emory.edu
      • Principal Investigator: Pretesh R. Patel, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically confirmed high-risk prostate cancer fulfilling any one of the following criteria:

  • Gleason grade 8 or higher
  • cT3b (seminal vesicle involvement) or cT4
  • Prostate specific antigen [PSA] > 20 (or PSA >10 if on finasteride)
  • Clinically or pathologically positive regional lymph nodes within the inguinal, external iliac, internal iliac, obturator, peri-rectal, pre-sacral, common iliac, or lower para-oaortc (inferior to the L2-L3 interspace) basins
• Zubrod performance status 0-2
• Complete blood cell (CBC)/differential obtained within 90 days prior to registration on study
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 60 days prior to registration on study)
• Platelets >= 100,000 cells/mm^3 (obtained within 60 days prior to registration on study)
• Hemoglobin >= 8.0 g/dl (obtained within 60 days prior to registration on study) (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Patient must be able to provide study specific informed consent

Exclusion Criteria:

• Absence of bone metastasis by bone scan or metabolic imaging (e.g. NaF PET, FACBC PET, PSMA PET, etc.) within 90 days prior to registration.
• Absence of distant lymph node metastasis by CT and/or MRI within 90 days prior to registration.
• Previous radical surgery (prostatectomy) or cryosurgery for prostate cancer
• Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy fields
• Uncontrolled intercurrent illness including, but not limited to, inflammatory bowel disease, human immunodeficiency virus infection, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (proton beam therapy); Patients undergo conventionally fractionated proton beam therapy daily on Monday-Friday directed to the prostate, pelvic lymph nodes, and para-aortic lymph nodes. Patients may receive an optional high-dose rate brachytherapy boost. Androgen deprivation therapy is required.

Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Survey Administration; Ancillary studies; Radiation: High-Dose Rate Brachytherapy; Receive high-dose rate brachytherapy boost; Other Names: Brachytherapy, High Dose; Radiation: Proton Beam Radiation Therapy; Undergo proton beam therapy; Other Names: Proton Radiation Therapy; PBRT; Proton; Radiation, Proton Beam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute grade 2+ gastrointestinal (GI) toxicity	The rate of grade 2+ gastrointestinal toxicity within 30 days of receiving radiation therapy (RT) will be measured. It will be compared to the theorized reduction to 24% toxicity using the exact binomial test. Assessments are based on version 5 Common Terminology Criteria for Adverse Events (CTCAE), and the worst severity of GI toxicity will be assessed.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute grade 2+ genitourinary (GU) toxicity rate	The rate of grade 2+ genitourinary toxicity within 30 days of receiving radiation therapy (RT) will be measured. Assessments are based on version 5 CTCAE, and the worst severity of GU toxicity will also be assessed.	Up to 3 years
Optimal frequency of cone beam computed tomography (CT)	Will determine the optimal frequency of cone beam CT during treatment and assess subsequent need for adaptive re-planning. The feasibility of extended-field proton irradiation of high-risk prostate cancer will be estimated using a re-planning rate of less than 10%. The re-planning rate will be estimated as binary variable, yes or no. The exact 95% confidence interval (CI) around the 10 % re-planning count based on the binomial distribution for the estimated 30 patients will be used (0.021-0.265). The study will be deemed feasible if the observed rate is not higher than the upper bound of the estimated 95% CI.	Through study completion, an average of 1 year
Patient reported health related quality of life (QOL) - PRO-CTCAU GI	Assessed using Patient Reported Outcomes-CTCAE GI toxicity	Up to 3 years
Patient reported health related quality of life (QOL) - PRO-CTCAU GU	Assessed using Patient Reported Outcomes-CTCAE GU toxicity	Up to 3 years
Patient reported health related quality of life (QOL) - IPSS	International Prostate Symptom Score (IPSS)	Up to 3 years
Patient reported health related quality of life (QOL) - EPIC-CP	Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP)	Up to 3 years
Chronic GI Toxicity	The rate of any grade gastrointestinal toxicity occurring after 90 days from the completion of radiation therapy(RT). Assessments are based on version 5 Common Terminology Criteria for Adverse Events (CTCAE), and the worst severity of GI toxicity will be assessed.	Up to 3 years
Chronic GU Toxicity	The rate of any grade genitourinary toxicity occurring after 90 days from the completion of radiation therapy(RT). Assessments are based on version 5 Common Terminology Criteria for Adverse Events (CTCAE), and the worst severity of GU toxicity will be assessed.	Up to 3 years
Biochemical failure	Assessed by the Phoenix definition (prostate specific antigen [PSA] >= 2 ng/ml over the nadir PSA).	Baseline up to pre-RT

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Pretesh R Patel, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: January 8, 2021
• First Submitted That Met QC Criteria: January 21, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Study00000329; P30CA138292 (U.S. NIH Grant/Contract); NCI-2020-07113 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RAD5131-20 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Results of the trial and not individual patient data will be shared. The study protocol, consent, and investigator's brochure will be available. The statistical plan is incorporated into the protocol, along with inclusion and exclusion criteria.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes