Randomized Trial of Five or Two MRI-Guided Adaptive Radiotherapy Treatments for Prostate Cancer (FORT)

Randomized Phase II Trial of Five or Two MRI-Guided Adaptive Radiotherapy Treatments for Prostate Cancer

The study is a randomized study that compares 5 radiation therapy treatments to 2 radiation therapy treatments in men with low or intermediate-risk prostate cancer.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Radiation Therapy

Detailed Description

This study is a randomized non-inferiority trial comparing 5 to 2 radiotherapy treatments using an MRI linear accelerator for men with low or intermediate-risk prostate cancer electing for definitive radiotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pragya Yadav, Ph.D; Phone Number: 6469622199; Email: pry2003@med.cornell.edu
• Study Contact Backup: Name: Raquel Downing, Ph.D.; Phone Number: 6469622196; Email: rad4012@med.cornell.edu

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX4 6LB
    • Recruiting
    • Genesis Care
    • Contact: Rabia Bhatti; Email: Rabia.Bhatti@genesiscare.co.uk
    • Principal Investigator: Philip Camilleri, M.D.
• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
      • Contact: Pragya Yadav, Ph.D.; Phone Number: 646-962-2199; Email: pry2003@med.cornell.edu
      • Principal Investigator: Himanshu Nagar, M.D.
      • Contact: Raquel Downing, Ph.D; Phone Number: 646-962-2196; Email: rad4012@med.cornell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men aged >=18 with histologically confirmed low or intermediate risk prostate cancer per NCCN guidelines.
• ECOG 0 - 1
• IPSS < 18
• Ability to receive MRI-guided radiotherapy.
• Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.
• Patients with a prior or concurrent disease whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the Principal Investigator.

Exclusion Criteria:

• Prior history of receiving pelvic radiotherapy.
• Patient with history of inflammatory bowel disease.
• MRI Prostate Volume > 80 cc
• MRI Stage > T3a
• Unilateral or bilateral hip replacements.
• History of bladder neck or urethral stricture.
• TURP < 8 weeks prior to radiotherapy
• Metastatic (pelvic nodal or distant) disease on CT, Bone, Fluciclovine, and/or PSMA PET scan

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: 5 radiation treatments - ARM 1; Patients randomized to ARM 1 will receive 37.5 in 5 radiotherapy treatments.	Radiation: Radiation Therapy; Eligible subjects will be randomly assigned to 5 or 2 fraction treatment groups in a 1:1 ratio using a computer-generated randomization scheme. After consent and eligibility verification, patients will undergo CT/MRI simulation and radiotherapy planning. Patients will receive treatment to the prostate +/- seminal vesicles per treating physician's discretion in either 37.5 Gy in 5 fractions or 25 Gy in 2 fractions. SIB use is at treating physician's discretion and should be concordant with imaging and biopsy findings with no PTV expansion. Subjects on 5 fraction arm should be treated on non-consecutive days. Subjects on the 2 fraction arm must have >72 hours between beginning of each fraction.
Active Comparator: 2 radiation treatments - ARM 2; Patients randomized to ARM 2 will receive 25 Gy in 2 radiotherapy treatments.	Radiation: Radiation Therapy; Eligible subjects will be randomly assigned to 5 or 2 fraction treatment groups in a 1:1 ratio using a computer-generated randomization scheme. After consent and eligibility verification, patients will undergo CT/MRI simulation and radiotherapy planning. Patients will receive treatment to the prostate +/- seminal vesicles per treating physician's discretion in either 37.5 Gy in 5 fractions or 25 Gy in 2 fractions. SIB use is at treating physician's discretion and should be concordant with imaging and biopsy findings with no PTV expansion. Subjects on 5 fraction arm should be treated on non-consecutive days. Subjects on the 2 fraction arm must have >72 hours between beginning of each fraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the number of patient-reported GI symptoms using the Expanded Prostate Cancer Index Composite (EPIC)	The primary objective is to demonstrate that 2 treatments of radiotherapy does not significantly increase patient-reported Gastrointestinal (GI) and Genitourinary (GU) symptoms compared to 5 treatments of radiotherapy 2 years after treatment completion.	Baseline, 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the number of patient reported GI symptoms at specific intervals as measured by Expanded Prostate Cancer Index Composite (EPIC)	Compare patient-reported GI symptoms using the EPIC at end of RT and 3, 6, 12, and 60 months from end of treatment. Expanded Prostate Cancer Index Composite (EPIC) short form questionnaire. The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Scores range from 0 to 100, lower scores indicate worse outcomes and higher EPIC scores represent better outcomes. Adverse events can be unexpected or expected, related to treatment.	Baseline, 1 week , 3months, 6 months, 12 months and 60 months
Change in the number of patient reported GU symptoms at specific intervals as measured by Expanded Prostate Cancer Index Composite (EPIC)	Compare patient-reported GU symptoms using the EPIC at end of RT and 3, 6, 12, and 60 months from end of treatment. Expanded Prostate Cancer Index Composite (EPIC) short form questionnaire. The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Scores range from 0 to 100, lower scores indicate worse outcomes and higher EPIC scores represent better outcomes. Adverse events can be unexpected or expected, related to treatment.	Baseline, 1 week, 3months, 6 months, 12 months and 60 months
Change in the number of patient reported sexual symptoms at specific intervals as measured by Expanded Prostate Cancer Index Composite (EPIC)	Compare patient-reported sexual symptoms using the EPIC at end of RT and 3, 6, 12, 24, and 60 months from end of treatment. Expanded Prostate Cancer Index Composite (EPIC) short form questionnaire. The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Scores range from 0 to 100, lower scores indicate worse outcomes and higher EPIC scores represent better outcomes. Adverse events can be unexpected or expected, related to treatment.	Baseline, 1 week, 3months, 6 months, 12 months and 60 months
Time to Progression (TTP)	Compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (PCSM).	3 months
Time to Progression (TTP)	Compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (PCSM).	6 months
Time to Progression (TTP)	Compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (PCSM).	12 months
Time to Progression (TTP)	Compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (PCSM).	60 months
Compare Overall Survival Rates	Compare Overall Survival (OS) in patients among the two arms, 37.5 Gy in 5 fractions and 25 Gy in 2 fractions.	3 months
Compare Overall Survival Rates	Compare Overall Survival (OS) in patients among the two arms, 37.5 Gy in 5 fractions and 25 Gy in 2 fractions.	6 months
Compare Overall Survival Rates	Compare Overall Survival (OS) in patients among the two arms, 37.5 Gy in 5 fractions and 25 Gy in 2 fractions.	12 months
Compare Overall Survival Rates	Compare Overall Survival (OS) in patients among the two arms, 37.5 Gy in 5 fractions and 25 Gy in 2 fractions.	60 months
prostate cancer specific survival	compare prostate cancer specific survival in patients among the two arms, 37.5 Gy in 5 fractions and 25 Gy in 2 fractions.	3 months
prostate cancer specific survival	compare prostate cancer specific survival in patients among the two arms, 37.5 Gy in 5 fractions and 25 Gy in 2 fractions.	6 months
prostate cancer specific survival	compare prostate cancer specific survival in patients among the two arms, 37.5 Gy in 5 fractions and 25 Gy in 2 fractions.	12 months
prostate cancer specific survival	compare prostate cancer specific survival in patients among the two arms, 37.5 Gy in 5 fractions and 25 Gy in 2 fractions.	60 months

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Progenics Pharmaceuticals, Inc.; Viewray Inc.
• Investigators: Principal Investigator: Himanshu Nagar, M.D., Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): July 30, 2021

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Low or intermediate risk prostate cancer; Definitive radiotherapy; MRI Linear accelerator
• 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: 21-02023315

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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