Hypofractionated Whole-Pelvis Radiotherapy (WPRT) vs Conventionally-Fractionated WPRT in Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this research study is to determine if 5 (five) fractions of external radiotherapy with higher radiation doses per fraction to the pelvis leads to similar results to the standard of care external radiotherapy treatment that is comprised of 25 fractions of external radiotherapy with lower radiation doses per fraction to the pelvis. This study aims to investigate the impact in quality of life associated with hypofractionated Whole Pelvis Radiotherapy (WPRT) in comparison to conventionally-fractionated WPRT in patients with unfavorable-intermediate and high-risk prostate cancers. This information is valuable as hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if proven to be well-tolerated and effective. Therefore, this study aims to provide a more rational justification for use of hypofractionated WPRT in future larger randomized trials by comparing this strategy with the current standard of care. This study will also provide an initial understanding of the toxicity profile and cancer control associated with hypofractionated WPRT and High Dose Rate Brachytherapy (HDR-BT).

Official Title
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Is Hypofractionated Whole-Pelvis Radiotherapy (WPRT) as Well Tolerated as Conventionally-Fractionated WPRT in Prostate Cancer Patients? (HOPE-Trial)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Conventionally-fractionated WPRT
* Radiation: Hypofractionated WPRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older Study Informed Consent provided Pathologically proven diagnosis of prostatic adenocarcinoma Unfavorable intermediate risk [with greater than 15% chance of node involvement based on Memorial Sloan Kettering Cancer Center (MSKCC) nomogram https://www.mskcc.org/nomograms/prostate] or high or very-high-risk prostate cancer based on National Comprehensive Cancer Network (NCCN) classification [Prostatic Specific Antigen (PSA) > 20 ng/mL or clinical cT3a or cT3b or Gleason 8-10] Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 No prior history of pelvic irradiation, brachytherapy, cryosurgery, High-Intensity Focused Ultrasound (HIFU), Transurethral Resection of the Prostate (TURP) or radical prostatectomy Exclusion Criteria: Presence of nodal or distant metastasis, as confirmed by Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) of the chest/abdomen/pelvis and bone scan within 45 days of randomization Plan for adjuvant docetaxel post-radiotherapy Serious medical comorbidities or other contraindications to HDR-BT Presence of inflammatory bowel disease Presence of connective tissue disease Medically unfit for general anesthesia Unable or unwilling to complete questionnaires

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 |
| --- | --- |
| Active Comparator: Conventionally-fractionated WPRT<br>15 Gy HDR brachytherapy boost will be administered followed by 45 Gy WPRT in 25 fractions. Androgen Deprivation Therapy (ADT) may also be prescribed at the discretion of the treating physician. | Radiation: Conventionally-fractionated WPRT<br>* Total dose: 45 Gy in 25 fractions WPRT<br>|
| Experimental: Hypofractionated WPRT<br>15 Gy HDR brachytherapy boost will be administered followed by 25 Gy WPRT in 5 fractions. Androgen Deprivation Therapy (ADT) may also be prescribed at the discretion of the treating physician. | Radiation: Hypofractionated WPRT<br>* Total dose: 25 Gy in 5 fractions WPRT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (QOL) - late bowel function as measured by the EPIC questionnaire | Late bowel function as reported by the patient using the standardized questionnaire Expanded Prostate Cancer Index Composite (EPIC) sub-domain approximately 1 year after the end of treatment. The EPIC questionnaire contains 32 questions measuring patient function. Each question has a response option ranging from 0 or 1 (best) to 3, 4, or 5 (worst). The responses then correlate to a scoring scale of 0 to 100, where 0 is the best and 100 is the worst. The values vary from 0 to 100 for each question. The scores can then be added to come up with an overall quality of life score. | I year post treatment (approximately 3 years and 2 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life - acute urinary and sexual QOL as measured by the EPIC questionnaire | Acute urinary and sexual QOL as reported by the patient using the standardized questionnaire Expanded Prostate Cancer Index Composite (EPIC) urinary and sexual domains. The EPIC questionnaire contains 32 questions measuring patient function. Each question has a response option ranging from 0 or 1 (best) to 3, 4, or 5 (worst). The responses then correlate to a scoring scale of 0 to 100, where 0 is the best and 100 is the worst. The values vary from 0 to 100 for each question. The scores can then be added to come up with an overall quality of life score. | 6 weeks post treatment (approximately 2 years and 3 months) | 
| Quality of Life - acute bowel toxicity as measured by the EPIC questionnaire | Acute bowel function as reported by the patient using the standardized questionnaire Expanded Prostate Cancer Index Composite (EPIC) approximately 6 weeks after the end of treatment. The EPIC questionnaire contains 32 questions measuring patient function. Each question has a response option ranging from 0 or 1 (best) to 3, 4, or 5 (worst). The responses then correlate to a scoring scale of 0 to 100, where 0 is the best and 100 is the worst. The values vary from 0 to 100 for each question. The scores can then be added to come up with an overall quality of life score. | 6 weeks post treatment (approximately 2 years and 3 months) | 
| Quality of Life - late bowel bother as measured by the EPIC questionnaire | Late bowel bother as reported by the patient using the standardized questionnaire Expanded Prostate Cancer Index Composite (EPIC) sub-domain approximately 1 year after the end of treatment. The EPIC questionnaire contains 32 questions measuring patient function. Each question has a response option ranging from 0 or 1 (best) to 3, 4, or 5 (worst). The responses then correlate to a scoring scale of 0 to 100, where 0 is the best and 100 is the worst. The values vary from 0 to 100 for each question. The scores can then be added to come up with an overall quality of life score. | I year post treatment (approximately 3 years and 2 months) | 
| Quality of Life - late urinary and sexual QOL as measured by the EPIC questionnaire | Late urinary and sexual QOL as reported by the patient using the standardized questionnaire Expanded Prostate Cancer Index Composite (EPIC). The EPIC questionnaire contains 32 questions measuring patient function. Each question has a response option ranging from 0 or 1 (best) to 3, 4, or 5 (worst). The responses then correlate to a scoring scale of 0 to 100, where 0 is the best and 100 is the worst. The values vary from 0 to 100 for each question. The scores can then be added to come up with an overall quality of life score. | I year post treatment (approximately 3 years and 2 months) | 
| International Prostate Symptom Score (IPSS) | International Prostate Symptom Score (IPSS) as reported by the patient at 6 weeks, 1 year, and 2 years post treatment. The IPSS is a tool used for monitoring symptoms of prostate enlargement (benign prostatic hyperplasia). There are 7 questions related to urinary function. Responses are on a scale from 0 (best) to 5 (worst). Responses are added to come up with a total score, measuring if the patient is mildly symptomatic, moderately symptomatic, or severely symptomatic. There is 1 quality of life question related to urinary symptoms. Responses are on a scale from 0 (best) to 6 (worst). | 6 weeks post treatment (approximately 2 years and 3 months), 1 year post treatment (approximately 3 years and 2 months) and 2 years post treatment (approximately 4 years and 2 months) | 
| Toxicity - urinary, bowel, and sexual as measured by CTCAE version 4.0 | Urinary, bowel, and sexual toxicity will be measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 4, at 6 weeks, 1 year, and 2 years post treatment. | 6 weeks post treatment (approximately 2 years and 3 months), 1 year post treatment (approximately 3 years and 2 months) and 2 years post treatment (approximately 4 years and 2 months) | 
| Prostatic Specific Antigen (PSA) curve | PSA curve at 4 years post-treatment. | 4 years post treatment (approximately 6 years and 2 months) | 
| Prostatic Specific Antigen (PSA) Nadir | PSA nadir at 4 years post-treatment. | 4 years post treatment (approximately 6 years and 2 months) | 
| Cost Effectiveness of Hypofractionated WPRT | Cost effectiveness analysis of the hypofractionated arm in comparison to the conventionally fractionated treatment arm. | End of study (approximately 7 years and 2 months) | 
| Overall Survival | The time from randomization to death from any cause. | End of study (approximately 7 years and 2 months) | 
| Biochemical Failure-Free Survival | The time from randomization to biochemical failure (based on the Phoenix definition) or death from any cause, whichever occurs first. | End of study (approximately 7 years and 2 months) | 
| Freedom from Local Failure | The time from randomization to first local failure. | End of study (approximately 7 years and 2 months) | 
| Freedom from Regional Failure | The time from randomization to first regional failure. | End of study (approximately 7 years and 2 months) | 
| Androgen Deprivation Therapy Free Survival | The time from randomization to start of salvage ADT, death or last follow-up. | End of study (approximately 7 years and 2 months) | 
| Metastasis Free Survival | The time from randomization to development of metastasis, death or last follow-up. | End of study (approximately 7 years and 2 months) | 
| Prostate Cancer Free Survival | The time from randomization to death attributed to prostate cancer. | End of study (approximately 7 years and 2 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unfavorable intermediate risk, High risk