Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer

Prostate Cancer Adenocarcinoma Clinical Trial

— Hypo-FLAME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02853110
• Other study ID #: NL53719.041.15a
• Status: Completed
• Phase: Phase 2
• Start date: April 2016
• Est. completion date: November 1, 2018

Study information

• Verified date: December 2018
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: November 1, 2018
• Est. primary completion date: November 1, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Prostate Cancer Adenocarcinoma
• Prostatic Neoplasms

Intervention

Radiation:
• Hypo-FLAME study
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.

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Netherlands	NKI-AvL	Amsterdam
Netherlands	Radboudumc	Nijmegen
Netherlands	UMC Utrecht	Utrecht

Sponsors (4)

Lead Sponsor	Collaborator
UMC Utrecht	Radboud University, The Netherlands Cancer Institute, Universitaire Ziekenhuizen Leuven

Countries where clinical trial is conducted

Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	MRI side study	Quantify intrafraction motion of the prostate (in mm)	Within 5 weeks from start of radiotherapy
Other	Blood sampling	Radiogenomic analyses	Within 5 weeks from start of radiotherapy
Primary	Acute toxicity	The goal of the present study is to investigate whether a focal SBRT boost to the macroscopic tumor is feasible and associated with acceptable toxicity in addition to whole gland prostate SBRT. Toxicity will be assessed by the acute gastrointestinal (GI) and genitourinary (GU) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Acute toxicity is defined as toxicity occurring within 90 days after the first radiation treatment.	90 days after first radiation treatment
Secondary	Late toxicity	Late toxicity, assessed by the late GI and GU Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Late toxicity is defined as toxicity occurring after at least 90 days after the first radiation treatment.	10 years after last radiation treatment
Secondary	Quality of life - general	European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire	5 years after last radiation treatment
Secondary	Biochemical disease free survival (bDFS)	Biochemical disease free survival	10 years after last radiation treatment
Secondary	Quality of life - prostate specific	EORTC QLQ- PR25 questionnaire	5 years after last radiation treatment