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

June 1, 2020 updated by: L.G.W. Kerkmeijer, UMC Utrecht

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

571

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
    • Vlaans-Brabant
      • Leuven, Vlaans-Brabant, Belgium, 3000
        • University Hospitals Leuven
  • Netherlands
      • Utrecht, Netherlands, 3584CX
        • University Medical Center Utrecht
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500HB
        • Radboud UMC
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1066CX
        • NKI-AvL

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Radiation: 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.
Other Names:
  • normal dose
Experimental: 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.
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.
Other Names:
  • FLAME

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: Every six months for 10 years
PSA relapse is defined by the Phoenix definition (2005) as nadir +2ng/ml.
Every six months for 10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Establish and compare the rates of treatment-related toxicity.
Time Frame: Every six months until 10 years
Toxicity is scored by Common Toxicity Criteria (CTC). Every grade>2 is considered severe toxicity.
Every six months until 10 years
quality of life
Time Frame: every six months until 10 year
Quality of life is measured by: SF-36, EORTC-C30 and EORTC-PR25.
every six months until 10 year
Disease specific survival
Time Frame: every 6 montths until 10 years
Death with metastases is considered a death caused by the disease.
every 6 montths until 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UMC Utrecht

Investigators

  • Principal Investigator: Linda Kerkmeijer, MD, PhD, UMC Utrecht
  • Study Director: Uulke van der Heide, PhD, NKI

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

July 21, 2010

First Submitted That Met QC Criteria

July 22, 2010

First Posted (Estimate)

July 23, 2010

Study Record Updates

Last Update Posted (Actual)

June 2, 2020

Last Update Submitted That Met QC Criteria

June 1, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCU-FLAME

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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