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Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0

Phase 2
Active, not recruiting
Conditions
Prostate Adenocarcinoma
Prostate Cancer
Prostate Neoplasm
Interventions
Radiation: Hypo-FLAME 2.0 study
Registration Number
NCT04045717
Lead Sponsor
Universitaire Ziekenhuizen KU Leuven
Brief Summary

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

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
124
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Hypo-FLAME 2.0Hypo-FLAME 2.0 studySBRT 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).
Primary Outcome Measures
NameTimeMethod
Acute toxicity90 days after first radiation treatment

Acute toxicity is scored using the Common Terminology Criteria Adverse Events version 5.0.

Secondary Outcome Measures
NameTimeMethod
Quality of life - prostate specific5 years after first radiation treatment

European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PR25 questionnaire

Quality of life - general5 years after first radiation treatment

European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire

Biochemical disease free survival10 years after first radiation treatment

Biochemical disease free survival is defined by the Phoenix consensus definition.

Late toxicity10 years after first radiation treatment

Late toxicity is scored using the Common Terminology Criteria Adverse Events version 5.0.

Trial Locations

Locations (3)

University Hospitals Leuven

🇧🇪

Leuven, Belgium

The Netherlands Cancer Institute

🇳🇱

Amsterdam, Netherlands

Radboudumc

🇳🇱

Nijmegen, Netherlands

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