Trial document




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  DRKS00015647

Trial Description

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Title

Efficacy and Safety of Fractionated Stereotactic Radiation Therapy (FSRT) versus Single Fraction Stereotactic Radiosurgery (SRS) for Large Brain Metastases (2 - 4 cm)

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Trial Acronym

FSRT-Trial

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Advances in the systemic control of tumor progression have made it more and more important to improve the efficacy and tolerability of local radiotherapy for the treatment of brain metastases. It can be assumed that patients will require local radiotherapy for an increasing number of cerebral metastases during the course of their disease history. Since the risk of treatment failure and side effects increases exponentially with the number of metastases, it is essential that the administered type of local radiotherapy be as effective and tolerable as possible. Both stereotactic radiosurgery and fractionated stereotactic radiotherapy are common standard treatments for the treatment of patients with brain metastases. However, no randomized controlled trial comparing FSRT (Fractionated Stereotactic Radiation Therapy) with SRS (Single Fraction Stereotactic Radiosurgery) has been performed so far. This study was therefore designed to compare FSRT and SRS for the treatment of large brain metastases in order to optimize treatment of patients with brain metastases.

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Brief Summary in Scientific Language

Safe and tolerable control of brain metastases is becoming increasingly important, but there is limited evidence on the optimal treatment regimen for patients with large brain metastases. Single-fraction stereotactic radiosurgery (SRS) according to the RTOG 9005 guidelines of the Radiation Therapy Oncology Group (RTOG) is the current gold standard for the treatment brain metastases measuring 2 to 4 cm in diameter. However, there is evidence suggesting that fractionated stereotactic radiotherapy (FSRT) might be significantly better for these patients with large brain metastases in terms of local control and toxicity.
FSRT is frequently used to treat large brain metastases in routine clinical practice, but has never been compared to single-fraction SRS in a randomized controlled trial so far. This study was therefore designed to determine whether FSRT with a dose of 12 x 4 Gy and a 2-mm safety margin is superior to single-fraction SRS according to RTOG 9005 criteria (gold standard) for the treatment of large brain metastases in terms of tumor control and CNS side effects.

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Organizational Data

  •   DRKS00015647
  •   2018/10/05
  •   [---]*
  •   yes
  •   Approved
  •   151_13 B, Ethik-Kommission der Friedrich-Alexander-Universität Erlangen-Nürnberg
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   C79.3 -  Secondary malignant neoplasm of brain and cerebral meninges
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Interventions/Observational Groups

  •   Single-fraction stereotactic radiosurgery (SRS) with a total dose of 1 x 18 Gy (2-3 cm) or 1 x 15 Gy (3-4 cm), respectively, delivered to the margin of the metastasis according to RTOG 9005 guidelines (gold standard)
  •   Fractionated stereotactic radiotherapy (FSRT) with a total dose of 48 Gy in 12 fractions of 4 Gy each, with a safety margin of 2 mm
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   N/A
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Primary Outcome

Improvement of local control of irradiated brain metastases

Primary endpoint: Time to local progression - TTLP

Local progression will be defined according to the RANO BM (Response assessment in neuro-oncology Brain Metastases) criteria by an increase of at least 20% in the longest diameter of the metastasis relative to nadir or baseline. In addition to the relative increase of 20% the lesion must increase by an absolute value of 5 mm or more.

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Secondary Outcome

Improvement of the tolerability of local radiotherapy, as measured based on the endpoints CNS toxicity and, in particular, radiation necrosis in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
(Assessments 6 weeks and 3 months after radiotherapy, then every 3 months for a total of 24 months)

Improvement of the local control of irradiated brain metastases, as determined based on volumetric criteria. Volumetric criteria may have important methodological advantages over traditional endpoints for the identification of treatment failure, especially in the case of large brain metastases. This study aims to improve our understanding of volumetric criteria and helps to further establish them.
(MRI 6 weeks and 3 months after radiotherapy, then every 3 months for a total of 24 months)

Quality of Life (EORTC QLQ-C30 and QLQ-BN20)
(Assessments 6 weeks and 3 months after radiotherapy, then every 3 months for a total of 24 months)

Improvement of local progression-free survival

Improvement of overall survival

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
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Recruitment

  •   Planned
  •   2019/01/15
  •   302
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. Age ≥ 18 years (no upper age limit)
2. Karnofsky Performance Scale (KPS) score >50
3. Life expectancy > 3 months
4. 1 to 4 brain metastases from a solid tumor
5. Indication for local radiotherapy of one or more brain metastases measuring 2 to 4 cm in diameter
6. Ability to understand the contents of the protocol and consent to participate, in writing
7. Written informed consent before enrollment in the study

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Exclusion Criteria

1. Whole brain radiotherapy completed ≤ 6 weeks before study treatment or planned whole brain radiotherapy following local radiotherapy
2. Prior radiotherapy of the metastasis or metastases to be irradiated in the present study
3. Relevant overlap of prior radiotherapy fields, cerebral or otherwise, with the metastasis or metastases to be irradiated in the present study
4. Location of metastasis to be irradiated in the brainstem.
5. Total of > 6 brain metastases, including previous metastases, at the time of inclusion in the study.
6. Contraindications to magnetic resonance imaging (e.g., metal implants, cardiac pacemaker, claustrophobia)
7. If a metastasis to be irradiated cannot be adequately differentiated in high-resolution, contrast-enhanced T1-weighted imaging for target volume delineation
8. Pregnant or nursing women
9. Women and men of reproductive age who are unwilling or unable to ensure reliable contraception during treatment
10. Chronic drug, medication or alcohol abuse
11. Psychological, familial, sociological, or geographical condition that would preclude study compliance
12. Nursing care patients
13. Inability to speak and understand German
14. Simultaneous participation in another clinical trial

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Addresses

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    • Universitätsklinikum Erlangen
    • Maximiliansplatz 2
    • 91054  Erlangen
    • Germany
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    • Universitätsklinikum Erlangen
    • Mr.  Dr. med.  Florian  Putz 
    • Universitätsstr. 27
    • 91054  Erlangen
    • Germany
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    • Universitätsklinikum Erlangen
    • Mr.  Dr. med.  Florian  Putz 
    • Universitätsstr. 27
    • 91054  Erlangen
    • Germany
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Sources of Monetary or Material Support

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    • Universitätsklinikum Erlangen
    • Maximiliansplatz 2
    • 91054  Erlangen
    • Germany
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Status

  •   Recruiting planned
  •   [---]*
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.