Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer (Hypo-FLAME)

UMC Utrecht

Status and phase

Completed

Phase 2

Conditions

Prostate Cancer Adenocarcinoma

Treatments

Radiation: Hypo-FLAME study

Study type

Interventional

Funder types

Other

Identifiers

NCT02853110

NL53719.041.15a

Details and patient eligibility

About

The hypo-FLAME study is a multicenter phase II study (n=100) to investigate whether a focal SBRT boost to the MRI-defined macroscopic tumor volume is feasible and associated with acceptable toxicity in addition to whole gland prostate SBRT.

Full description

Rationale: Hypofractionation with a stereotactic body radiotherapy (SBRT) technique for prostate cancer produces excellent treatment outcome in terms of survival and toxicity and is much more convenient than the current fractionation scheme. Local recurrence occurs most frequently at the site of the primary or dominant tumor location prior to treatment. Therefore dose escalation at the site of the primary tumor may improve disease control.

Objective: The main goal of this phase II study is to investigate whether a focal ablative SBRT boost to the macroscopic tumor is feasible and associated with acceptable toxicity in addition to whole gland prostate SBRT. The secondary objectives of this study are: late toxicity, quality of life (QoL) and biochemical disease free survival (bDFS). Furthermore, two side-studies are incorporated in this phase II study: 1) a weekly MRI will be performed to prepare for future MRI-guided (MR-linac) treatment without gold fiducial markers and 2) blood sampling for translational research (radiogenomics) and Biobank purposes.

Study design: Prospective multicenter interventional study on whole gland prostate SBRT using MRI for focal boost in 100 consecutive intermediate or high risk prostate cancer patients.

Study population: One hundred patients with histologically proven prostate adenocarcinoma with intermediate risk or high risk disease. Patients referred for external beam radiotherapy (EBRT) who fulfill 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 by external beam radiotherapy with a SBRT technique with 35 Gy in 5 weekly fractions and an additional simultaneously integrated focal boost to the tumor nodule(s) visible on MRI up to 50 Gy. In addition, patients will be asked to undergo 5 additional MRI scans (~15 min/scan) without contrast enhancement prior to each radiation session as well as blood sampling for translational research (radiogenomics) and Biobank purposes.

Main study parameters/endpoints: The primary endpoints of this study are acute gastrointestinal (GI) and genitourinary (GU) toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Secondary endpoints are late GI and GU toxicity, QoL, and bDFS. Simultaneously, two side-studies will be performed, i.e. to prepare for MRI-guided radiotherapy and blood sampling for translational research (radiogenomics) and Biobank purposes.

Enrollment

100 patients

Sex

Male

Ages

18 to 100 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Men ≥ 18 years with histologically confirmed prostate adenocarcinoma
Intermediate-risk prostate cancer or high-risk prostate cancer, defined as at least one of the following risk criteria: clinical T-stage T2b, T2c or T3a (defined on MRI) or T3b with less than 5 mm invasion in the seminal vesicle, Gleason sum score ≥ 7, PSA ≥ 10 ng/mL
Prostate tumor nodule visible on MRI
Ability to give written informed consent and willingness to return for follow-up

Exclusion criteria

Prior pelvic radiotherapy, transurethral prostate resection or prostatectomy
Unsafe to have gold fiducial marker implantation
Contraindications to MRI according to the Radiology Department guidelines (metal implants, non-compatible cardiac device, allergy to Gadolinium, severe renal dysfunction or severe claustrophobia)
Evidence of lymph node involvement or distant metastatic disease
Clinical T-stage > T3b with ≥ 5 mm invasion in the seminal vesicle
World Health Organization (WHO) performance score > 2
International prostate symptoms score (IPSS score) ≥ 15
PSA > 30 ng/mL