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

NCT01168479 | Completed Phase 3 DMC

• 1 other identifier: UMCU-FLAME
• Study Type: interventional
• Target: 571
• Locations: 2 countries
• Sites: 4

Brief 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.

Conditions

Prostate Cancer; Radiotherapy; MRI

Keywords

prostate cancer; external beam radiotherapy; dose escalation; dose painting; 95Gy in 35 fractions; MRI; FLAME

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Establish and compare the rates of treatment-related toxicity.

  Every six months until 10 years

• quality of life

  every six months until 10 year

• Disease specific survival

  every 6 montths until 10 years

Study Arms (2)

standard arm

ACTIVE COMPARATOR

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

FLAME boost

EXPERIMENTAL

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

Interventions

FLAME boost RADIATION

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.

Also known as: FLAME

FLAME boost

standard arm RADIATION

The standard arm receives the current gold standard, namely 77Gy to the prostate in 35 fractions of 2.2 Gy, 5 times per week.

Also known as: normal dose

standard arm

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (4)

University Hospitals Leuven

Leuven, Vlaans-Brabant, 3000, Belgium

Location

Radboud UMC

Nijmegen, Gelderland, 6500HB, Netherlands

Location

NKI-AvL

Amsterdam, North Holland, 1066CX, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location

Related Publications (6)

• Kowalchuk RO, Kim H, Harmsen WS, Jeans EB, Morris LK, Mullikin TC, Miller RC, Wong WW, Vargas CE, Trifiletti DM, Phillips RM, Choo CR, Davis BJ, Beriwal S, Tendulkar RD, Stish BJ, Breen WG, Waddle MR. Cost effectiveness of treatment strategies for high risk prostate cancer. Cancer. 2022 Nov 1;128(21):3815-3823. doi: 10.1002/cncr.34450. Epub 2022 Sep 7.

  PMID: 36070558 DERIVED

• Groen VH, Haustermans K, Pos FJ, Draulans C, Isebaert S, Monninkhof EM, Smeenk RJ, Kunze-Busch M, de Boer JCJ, van der Voort van Zijp J, Kerkmeijer LGW, van der Heide UA. Patterns of Failure Following External Beam Radiotherapy With or Without an Additional Focal Boost in the Randomized Controlled FLAME Trial for Localized Prostate Cancer. Eur Urol. 2022 Sep;82(3):252-257. doi: 10.1016/j.eururo.2021.12.012. Epub 2021 Dec 23.

  PMID: 34953603 DERIVED

• Kerkmeijer LGW, Groen VH, Pos FJ, Haustermans K, Monninkhof EM, Smeenk RJ, Kunze-Busch M, de Boer JCJ, van der Voort van Zijp J, van Vulpen M, Draulans C, van den Bergh L, Isebaert S, van der Heide UA. Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):787-796. doi: 10.1200/JCO.20.02873. Epub 2021 Jan 20.

  PMID: 33471548 DERIVED

• van Schie MA, Janssen TM, Eekhout D, Walraven I, Pos FJ, de Ruiter P, Kotte ANTJ, Monninkhof EM, Kerkmeijer LGW, Draulans C, de Roover R, Haustermans K, Kunze-Busch M, Smeenk RJ, van der Heide UA. Knowledge-Based Assessment of Focal Dose Escalation Treatment Plans in Prostate Cancer. Int J Radiat Oncol Biol Phys. 2020 Nov 15;108(4):1055-1062. doi: 10.1016/j.ijrobp.2020.06.072. Epub 2020 Jul 3.

  PMID: 32629078 DERIVED

• Monninkhof EM, van Loon JWL, van Vulpen M, Kerkmeijer LGW, Pos FJ, Haustermans K, van den Bergh L, Isebaert S, McColl GM, Smeenk RJ, Noteboom J, Walraven I, Peeters PHM, van der Heide UA. Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial. Radiother Oncol. 2018 Apr;127(1):74-80. doi: 10.1016/j.radonc.2017.12.022. Epub 2018 Jan 11.

  PMID: 29336835 DERIVED

• Lips IM, van der Heide UA, Haustermans K, van Lin EN, Pos F, Franken SP, Kotte AN, van Gils CH, van Vulpen M. Single blind randomized phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial. Trials. 2011 Dec 5;12:255. doi: 10.1186/1745-6215-12-255.

  PMID: 22141598 DERIVED

Related 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'

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Linda Kerkmeijer, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Uulke van der Heide, PhD

  NKI

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: L.G.W. Kerkmeijer, MD, PhD

Study Record Dates

• First Submitted: July 21, 2010
• First Posted: July 23, 2010
• Study Start: September 1, 2009
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: June 2, 2020

Record last verified: 2020-06

Locations

BE (1); NL (3)