FLAME: Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer

Prostate Cancer Clinical Trial

— FLAME  

Official title:

FLAME: Single Blind Randomized Phase III Trial to Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01168479
• Other study ID #: UMCU-FLAME
• Status: Completed
• Phase: Phase 3
• Start date: September 2009
• Est. completion date: January 2016

Study information

• Verified date: June 2020
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Rationale: Dose escalation in external-beam irradiation has proven to benefit outcome in local prostate cancer. Randomized trials were performed up to doses of 78 Gy in 2 Gy fractions. Nevertheless, the five-year biochemical relapse rate still was approximately 35% in the high-dose arm. Therefore further dose escalation seems to be required. A feasibility study up to appr. 85 Gy on the entire prostate has already been performed and showed acceptable toxicity when combined with adequate position verification. Higher doses to the entire prostate are expected to increase severe toxicity. As local recurrences only occur at the site of the primary macroscopic tumour area the next step in increasing the dose should be an ablative boost to the macroscopic tumour alone, while electively irradiating the rest of the prostate to the current gold standard dose. Feasibility of this approach has been shown for an ablative dose of 95 Gy to the macroscopic tumour within the prostate.

Description:

Objective:

• Primary study objective: To demonstrate the superiority of the ablative microboost dose schedule regarding 5-year biochemical no evidence of disease rate compared to the current standard of care.

• Secondary study objectives: Establish and compare the rates of treatment-related toxicity, quality of life and disease-free survival.

Study design: Single blind prospective randomized controlled phase III trial.

Study population: Patients with intermediate or high risk adenocarcinoma of the prostate. Intermediate or high risk is defined according to the Ash et al. 2000 criteria as:

• One (intermediate-risk) or more (high-risk) factors: T2, or Gleasonscore=7, or iPSA 10-20 ng/mL

• One or more (high-risk) factors: T3, or Gleasonscore >7, or iPSA >20 ng/mL

Intervention: The standard arm receives the current gold standard, namely 77Gy to the prostate in 35 fractions of 2.2 Gy, 5 times per week. In the experimental arm patients receive in addition to the current gold standard of 77 Gy to the prostate an integrated boost to the macroscopically visible tumour to reach a total dose of 95 Gy in 35 fractions of 2.7 Gy, 5 times per week.

Main study endpoint: To decrease the five-year biochemical relapse rate with at least 10%.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Patients will have to fill in a quality of life questionnaire before and after the radiotherapy treatments. The risk associated with the increased dose to the macroscopic tumour is an increase of toxicity and a reduction of quality of life.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 571
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Prostate cancer patients scheduled for external beam radiotherapy using IMRT and fiducial marker-based position verification

• Intermediate and high risk prostate cancer, defined by Ash et al. 2000, namely:

• One or more factors: T2, or Gleasonscore >7, or iPSA > 10 ng/mL

• WHO score 0-2

Exclusion Criteria:

• Low risk prostate cancer, defined by Ash et al. 2000

• World Heath Organisation (WHO) score >2

• International Prostate Symptom Score (IPSS) >20

• If for any patient related reason an MRI cannot be performed

• If anticoagulation cannot be stopped temporarily regarding the implant of fiducial markers

• Previous prostatectomy (except from Trans Urethral Prostatectomy (TURP))

• TURP within 3 months from start treatment

• Previous pelvic irradiation

Related Conditions & MeSH terms

• MRI
• Prostate Cancer
• Prostatic Neoplasms
• Radiotherapy

Intervention

Radiation:
• FLAME boost
In the experimental arm patients receive in addition to the current gold standard of 77 Gy to the prostate an integrated boost to the macroscopically visible tumour to reach a total dose of 95 Gy in 35 fractions of 2.7 Gy, 5 times per week.
• standard arm
The standard arm receives the current gold standard, namely 77Gy to the prostate in 35 fractions of 2.2 Gy, 5 times per week.

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven	Vlaans-Brabant
Netherlands	NKI-AvL	Amsterdam	Noord-Holland
Netherlands	Radboud UMC	Nijmegen	Gelderland
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
UMC Utrecht

Countries where clinical trial is conducted

Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To demonstrate the superiority of the ablative microboost dose schedule regarding 5-year biochemical no evidence of disease rate compared to the current standard of care.	PSA relapse is defined by the Phoenix definition (2005) as nadir +2ng/ml.	Every six months for 10 years
Secondary	Establish and compare the rates of treatment-related toxicity.	Toxicity is scored by Common Toxicity Criteria (CTC). Every grade>2 is considered severe toxicity.	Every six months until 10 years
Secondary	quality of life	Quality of life is measured by: SF-36, EORTC-C30 and EORTC-PR25.	every six months until 10 year
Secondary	Disease specific survival	Death with metastases is considered a death caused by the disease.	every 6 montths until 10 years

External Links

•   Click here for more information about this study: FLAME 'Multicenter Randomized Phase III Trial to Investigate the Benefit of a Focal Lesion Ablative Microboost in patients treated with External Beam Radiotherapy for Localized Prostate Cancer'