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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M. van Vulpen, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01168479
First received: July 21, 2010
Last updated: July 4, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Prostate Cancer
Radiotherapy
MRI
Radiation: FLAME boost
Radiation: standard arm
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: FLAME: Single Blind Randomized Phase III Trial to Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    PSA relapse is defined by the Phoenix definition (2005) as nadir +2ng/ml.


Secondary Outcome Measures:
  • Establish and compare the rates of treatment-related toxicity. [ Time Frame: Every six months until 10 years ] [ Designated as safety issue: Yes ]
    Toxicity is scored by Common Toxicity Criteria (CTC). Every grade>2 is considered severe toxicity.

  • quality of life [ Time Frame: every six months until 10 year ] [ Designated as safety issue: Yes ]
    Quality of life is measured by: SF-36, EORTC-C30 and EORTC-PR25.

  • Disease specific survival [ Time Frame: every 6 montths until 10 years ] [ Designated as safety issue: No ]
    Death with metastases is considered a death caused by the disease.


Enrollment: 567
Study Start Date: September 2009
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: FLAME

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01168479

Locations
Belgium
University Hospitals Leuven
Leuven, Vlaans-Brabant, Belgium, 3000
Netherlands
Radboud University
Nijmegen, Gelderland, Netherlands, 6500HB
NKI-AvL
Amsterdam, Noord-Holland, Netherlands, 1066CX
University Medical Center Utrecht
Utrecht, Netherlands, 3584CX
Sponsors and Collaborators
UMC Utrecht
Investigators
Principal Investigator: Marco van Vulpen, MD, PhD UMC Utrecht
Study Director: Uulke van der Heide, PhD AvL - NKI
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M. van Vulpen, MD, PhD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01168479     History of Changes
Other Study ID Numbers: UMCU-FLAME 
Study First Received: July 21, 2010
Last Updated: July 4, 2016
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by UMC Utrecht:
prostate cancer
external beam radiotherapy
dose escalation
dose painting
95Gy in 35 fractions
MRI
FLAME

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 23, 2016