Protons vs. Photons for High-risk Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess late gastro-intestinal side-effects comparing proton therapy to photon therapy in high-risk prostate cancer patients receiving whole pelvic irradiation.

Detailed Description
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Proton therapy (PT) is a radiation technique with possibility to spare normal pelvic organs: bladder, rectum and bowel for PC patients. Most PC patients treated with PT receive PT to the prostate gland alone. With PT, we aim to examine PC patients in high risk with both lymph node and prostate treatment will experience less late side effects with PT compared to photon treatment. The investigators propose a national open-labelled phase III randomized controlled trial (RCT) of proton therapy versus photon therapy of the prostate including the regional elective LN for localized/locally advanced prostate cancer patients combined with androgen deprivation therapy (ADT) aimed at 3 years. The investigators aim at reducing gastro-intestinal toxicity grad 2 more than 5 points, which is considered clinical significant, measured by mean Expanded Prostate Cancer Index Composite-26 (EPIC-26) bowel scores at 24 months and improve HRQOL. Secondary endpoints include morbidity, quality of life and survival data up to 10 years after treatment.

Official Title
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Lymph Node Radiation Therapy With Integrated Boost to Prostate for High-risk Prostate Cancer A Randomized Phase 3 Trial Comparing Photons vs. Protons

Conditions
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Prostate Cancer, Radiotherapy Side Effect

Intervention / Treatment
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* Radiation: Proton therapy
* Radiation: Photon therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified localized/locally advanced prostate cancer T1-3bN0M0 (TNM 8th edition). A clinical T4 is allowed if it is because of invasion into the bladder neck. Adenocarcinoma (mixed histology allowed as long as the adenocarcinoma component comprise more than 50%) Indication for elective lymph node irradiation PSA < 100 ng/mL Age ≥18 years Performance status 0-1 Life expectancy ≥ 10 years Able to understand and comply with the treatment protocol No evidence of inflammatory bowel disease Ability to adhere to procedures for study and follow-up Signed informed consent to participate in the study Exclusion Criteria: No previous treatment for prostate cancer Hip-prostheses Other metal devices in the pelvic region (except fiducials) Previous major abdominal/rectal surgery Any other malignancy the last five years except for basal or squamous cell skin cancer Unable to understand patient information or comply with treatment and safety instructions Unable to read and understand patient information due to cognitive disabilities or language (Danish).

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
Interventional Model Description: A randomized phase 3 study, randomizing 1:1 between photon vs. proton therapy for prostate cancer patients with high risk disease
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton therapy<br>Radiation: Proton Therapy 78 Gray (Gy) in 39 fractions with 56 Gy to the Pelvic Lymph Nodes (LN), 5 days a week. Androgen Deprivation Therapy (ADT) for three years, starting 3 months before Proton Therapy. | Radiation: Proton therapy<br>* Patients in the experimental arm will receive proton therapy within the same dose and fraction schedule as patients receiving photon therapy, which is standard treatment.<br>|
| Active Comparator: Photon Therapy<br>Radiation: Photon Therapy 78 Gy in 39 fractions with 56 Gy to the pelvic LN, 5 days a week. ADT for three years, starting 3 months before Photon Therapy. | Radiation: Photon therapy<br>* Patients in the photon arm will receive standard treatment with photon therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late gastrointestinal (GI) toxicity at year 2 compared to baseline using Expanded Prostate Cancer Index Composite-26 (EPIC-26) | Patient Reported Outcome The investigators aim at reducing gastro-intestinal toxicity grad 2 more than 5 points, which is considered clinically significant, measured by mean points, which is considered clinically significant. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late Genito-urinary (GU) and sexual toxicity ≥ 2 grade at year 2 and 5 compared to baseline (Common Terminology Criteria for Adverse Events (CTCAE) toxicity score (CTC_AE 5.0) | Physician Assessed Toxicity Number of Participants With Treatment-Related Adverse events as assessed by CTCAE v5.0 | 5 years | 
| Late GU and sexual toxicity at year 2, 5 and 10 compared to baseline (EPIC-26) | Patient Reported Outcome using on-line questionnaire to assess this outcome measure | 10 years | 
| Late GI toxicity at year 5 compared to baseline (EPIC-26) | Patient Reported Outcome using on-line questionnaire to assess this outcome measure.aim at reducing gastro-intestinal toxicity grad 2 more than 5 points, which is considered clinically significant, measured by mean points, which is considered clinically significant | 5 years | 
| Acute GI at start, at the end of therapy and week 12 compared to baseline (EPIC-26) | EPIC-26 | 12 weeks | 
| Acute GI at start, at the end of therapy and week 12 compared to baseline (CTC_AEv.5.0) | Physician Assessed Toxicity | 12 weeks | 
| Acute GU toxicity at start, at the end of therapy and week 12 compared to baseline (EPIC-26) | EPIC-26 | 12 weeks | 
| Acute GU toxicity at start, at the end of therapy and week 12 compared to baseline (CTC_AE v.5.0) | Physician Assessed Toxicity | 12 weeks | 
| General health related quality of life (QoL) at year 2, 5 and 10 compared to baseline (EORTC QLQ-C30) | Patient Reported Outcome General health related quality of life (QoL) at year 2, 5 and 10 (EORTC QLQ-C30) | 10 years | 
| Biochemical progression free survival (BCR), (Phoenix criteria) | blood test | 10 years | 
| Non-biochemical progression free survival (by imaging) | Radiology assesments | 10 years | 
| Overall survival (OS) | Follow up | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intensity Modulated Radiotherapy, Proton Therapy, High Risk