Clinical trial NCT04045717: Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0
Official title: Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Prostate Adenocarcinoma
Prostate Cancer
Prostate Neoplasm
Keywords: Stereotactic Body Radiotherapy
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: The Netherlands Cancer Institute
name: Radboud University Medical Center
name: Kom Op Tegen Kanker
First posted: 2019-08-05
Enrollment: 124
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Acute toxicity
timeFrame: 90 days after first radiation treatment
Secondary outcomes:
measure: Late toxicity
timeFrame: 10 years after first radiation treatment
measure: Quality of life - general
timeFrame: 5 years after first radiation treatment
measure: Quality of life - prostate specific
timeFrame: 5 years after first radiation treatment
measure: Biochemical disease free survival
timeFrame: 10 years after first radiation treatment
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Nijmegen
country: Netherlands
facility: Radboudumc
Study officials:
affiliation: UZ Leuven
name: Karin Haustermans, M.D. PhD
role: PRINCIPAL_INVESTIGATOR
References: