Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0

Study Overview
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Brief Summary
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The hypo-FLAME 2.0 study is a multicenter phase II study (n=124) investigating the feasibility and safety of a reduction in the overall treatment time of radiotherapy for prostate cancer patients, making use of hypofractionated stereotactic body radiotherapy with focal boosting. We are looking for the optimal overall treatment time for this treatment strategy in the Hypo-FLAME 2.0 trial. In this study the total treatment time will be halved (15 days) in comparison with the total treatment time in the former hypo-FLAME trial (29 days) (NCT02853110).

Detailed Description
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Rationale: External beam radiotherapy is one of the standard treatment options for patients with prostate cancer. The overall treatment time of a standard fractionated schedule varies between 7 and 8 weeks (i.e. 35-40 fractions, 5x/week). Recent studies have identified a proportionally longer overall treatment time as a potential adverse factor for treatment outcome in prostate cancer patients who were treated by conventional radiotherapy schedules. Furthermore shortening of the overall treatment time promotes patient convenience. An extreme shortening of the overall treatment time is possible by using hypofractionated treatment schedules with simultaneous integrated intraprostatic tumor boosting to overcome local recurrences. Objective: In this study we will investigate the feasibility and safety of a reduction in the overall treatment time of radiotherapy for prostate cancer patients, making use of hypofractionated stereotactic body radiotherapy with focal boosting. We are looking for the optimal overall treatment time for this treatment strategy in the Hypo-FLAME 2.0 trial. In this study the total treatment time will be halved (15 days) in comparison with the total treatment time in the former Hypo-FLAME trial (29 days). Besides a potential biological advantage, the reduced overall treatment time offers benefits with respect to patient convenience. Study population: One hundred twenty four patients with histologically proven intermediate- or high-risk prostate cancer will be included in this multicenter phase II study. Patients referred for external beam radiotherapy who fulfil the inclusion criteria and without any of the exclusion criteria will be included in the present trial after written informed consent. Intervention: Patients will be treated with a stereotactic body radiation therapy technique up to 35 Gray in 5 fractions of 7 Gray to the whole prostate gland. Additionally a simultaneously integrated focal boost to the macroscopic tumor nodule(s) visible on MRI up to 50 Gray (10 Gray/fraction) will be delivered. Treatment fractions will be delivered twice weekly, resulting in an overall treatment time of 2,5 weeks. Main study endpoints: The primary endpoint of this study is acute gastrointestinal and genitourinary toxicity, scored using the Common Terminology Criteria Adverse Events version 5.0. Secondary endpoints are late gastrointestinal and genitourinary toxicity, quality of life and biochemical disease free survival defined by the Phoenix consensus definition.

Official Title
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Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0

Conditions
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Prostate Adenocarcinoma, Prostate Cancer, Prostate Neoplasm

Intervention / Treatment
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* Radiation: Hypo-FLAME 2.0 study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men ≥ 18 years with histologically confirmed prostate adenocarcinoma Intermediate- or high-risk PCa, defined as at least one of the following risk criteria: Clinical stage: T2b, T2c, T3a or T3b with less than 5 mm invasion in the seminal vesicles (defined on MRI) N0 M0 Gleason sum score ≥ 7 PSA ≥ 10 ng/mL. Prostate tumor nodule visible on mpMRI Ability to give written informed consent and willingness to return for follow-up Exclusion Criteria: Prior pelvic radiotherapy or transurethral prostate resection Unsafe to have gold fiducial marker implantation, if gold fiducial markers are used for image guidance (non MR-linac) Contraindications to MRI according to the Radiology Department guidelines (metal implants, non-compatible cardiac device, allergy to gadolinium, severe renal dysfunction or severe claustrophobia) World Health Organization (WHO) performance score > 2 International prostate symptoms score (IPSS score) ≥ 15 PSA > 30 ng/mL

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypo-FLAME 2.0<br>SBRT technique with 35 Gy in 5 fractions to the whole prostate gland and an additional simultaneously integrated focal boost to the tumor nodule(s) visible on MRI up to 50 Gy (overall treatment time (OTT) = 15 days). | Radiation: Hypo-FLAME 2.0 study<br>* SBRT technique with 35 Gy in 5 fractions to the whole prostate gland and an additional simultaneously integrated focal boost to the tumor nodule(s) visible on MRI up to 50 Gy (overall treatment time (OTT) = 15 days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity | Acute toxicity is scored using the Common Terminology Criteria Adverse Events version 5.0. | 90 days after first radiation treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late toxicity | Late toxicity is scored using the Common Terminology Criteria Adverse Events version 5.0. | 10 years after first radiation treatment | 
| Quality of life - general | European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire | 5 years after first radiation treatment | 
| Quality of life - prostate specific | European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PR25 questionnaire | 5 years after first radiation treatment | 
| Biochemical disease free survival | Biochemical disease free survival is defined by the Phoenix consensus definition. | 10 years after first radiation treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stereotactic Body Radiotherapy