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Evaluation of Repeated Whole Brain Radiotherapy Versus Best Supportive Care for Multiple Brain Metastases. (ERASER)

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ClinicalTrials.gov Identifier: NCT03288272
Recruitment Status : Recruiting
First Posted : September 20, 2017
Last Update Posted : September 20, 2017
Sponsor:
Information provided by (Responsible Party):
Stephanie Combs, Technische Universität München

Brief Summary:

Whole Brain Radiotherapy (WBRT) has been established as the treatment standard in patients with multiple cerebral metastases from solid tumors. However, intracerebral recurrence is possible and a repeated WBRT may be indicated to improve intracerebral tumor control. Each institutsion offers different dosing regimens, which have all been published to be safe and effective. Some favor best supportive care only.

The current study protocol is aimed at evaluating primarily the toxicity as well as secondarily the local and loco-regional tumor control, overall survival and QoL after repeated WBRT using 2 different dose concepts (20 Gy in 10 Fx vs. 30 Gy in 15 Fx) compared to BSC.


Condition or disease Intervention/treatment Phase
Brain Metastasases Radiation: Whole Brain Radiotherapy Other: Best Supportive Care Phase 2

Detailed Description:

According to Nussbaum et al., 24-45% of cancer patients develop cerebral metastases during the course of the disease. Brain metastases are generally associated with a poor prognosis and high morbidity. Published median survival rates after WBRT are between 2 and 7 months. Standard of care in multiple BM is WBRT delivered as 30 Gy in 10 fractions, leading to modest palliation with a median survival of 3 to 5 months. Prognostic factors include the RPA-classification, performance status, response to steroids and evidence of systemic disease.

Unfortunately, intracerebral recurrence happens. For example, in the cohort of Meyners et al.(2010) on WBRT in relatively radioresistant tumors, median time to recurrence was 4.5months and the local control rates at 6 and 12 months post radiationem were 37% and 15%, respectively. Furthermore, the treatment of intracerebral recurrence after previous WBRT is challenging. In case of </= 3 recurrent BM, surgery or radiosurgery (RS) are options. One other option, especially in case of >3 recurrent BM is repeated WBRT. In this setting, one of the first reports on repeated WBRT was published by Cooper et al. in 1990. The authors reported on repeated WBRT (n=52) consisting of 25 Gy in 10 fractions. Response to reirradiation was seen in 42% of the patients. Furthermore, the patients improved by at least one level in their neurologic function status. Survival after second therapy averaged 5 months. In the report by Wong et al. (1996) median dose of retreatment (n=86) was 20 Gy. Resolution of symptoms was achieved in 27% of patients, partial improvement in 43% and no improvement or worsening of symptoms was seen in 29% of patients. The majority of patients had no significant toxicity secondary to re-irradiation. Five patients had radiographic abnormalities of their brain consistent with radiation-related changes. One patient had symptoms of dementia that was thought to be caused by radiotherapy. Sadikov et al. (2007) reported on 72 patients who underwent repeated WBRT for recurrent or progressive BM. The median survival after re-irradiation was 4.1 months. One patient was reported as having memory impairment and pituitary insufficiency after 5 months of progression-free survival.

In the report by Mayer et al. on re-irradiation tolerance of the human brain -in this analysis focused on recurrent glioma-, the authors concluded that radiation-induced brain tissue necrosis is found to occur at normalized tolerance doses of cumulative > 100 Gy.

The current study protocol is aimed at evaluating primarily the toxicity as well as secondarily the local and loco-regional tumor control, overall survival and QoL after repeated WBRT using 2 different dose concepts (20 Gy in 10 Fx vs. 30 Gy in 15 Fx) compared to BSC.

In the present trial, the primary endpoint toxicity as well as the secondary endpoints QoL, loco-regional progression-free survival, overall survival and imaging response in patients previously treated with WBRT requiring repeated WBRT for intracerebral tumor progression will be evaluated.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomization Best Supportive Care, Two Radiotherapy Dosing Regimens
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Repeated Whole Brain Radiotherapy Versus Best Supportive Care for Multiple Brain Metastases - the Randomized Trial ERASER.
Study Start Date : April 2016
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : May 2018

Arm Intervention/treatment
Active Comparator: Arm 1 - WBRT 10 x 2 Gy
Arm 1 - WBRT 10 x 2 Gy Whole brain radiotherapy with a total dose of 20 Gy in single fractions of 2 Gy
Radiation: Whole Brain Radiotherapy
Radiotherapy of the whole brain

Active Comparator: Arm 2 - WBRT 15 x 2 Gy
Arm 2 - WBRT 15 x 2 Gy Whole brain radiotherapy with a total dose of 30 Gy in single fractions of 2 Gy
Radiation: Whole Brain Radiotherapy
Radiotherapy of the whole brain

Active Comparator: Arm 3 - Best Supportive Care
Symptomatic treatment includes steroids, pain medication, nutritional support etc.
Other: Best Supportive Care
Best Supportive Care including nutrition, pain medication, steroids as needed




Primary Outcome Measures :
  1. Toxicity [ Time Frame: 3 months ]
    The primary endpoint is toxicity according to CTCAE after whole brain radiotherapy.


Secondary Outcome Measures :
  1. loco-regional progression-free survival [ Time Frame: 6 months ]
    follow-up and local control of brain metastases as well as loco-regional control

  2. Quality of Life (QOL) [ Time Frame: 6 months ]
    QOL

  3. Survival [ Time Frame: 6 months ]
    survival after radiotherapy



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • histologically confirmed malignancy
  • previous WBRT
  • MR-imaging confirmed cerebral metastases (>1)
  • age ≥ 18 years of age
  • Karnofsky Performance Score ³60
  • For women with childbearing potential, (and men) adequate contraception.
  • Ability of subject to understand character and individual consequences of the clinical trial
  • Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria

  • refusal of the patients to take part in the study
  • Patients who have not yet recovered from acute high-grade toxicities of prior therapies
  • Pregnant or lactating women
  • Participation in another clinical study or observation period of competing trials, respectively

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03288272


Contacts
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Contact: Stephanie E Combs, Prof. Dr. +49-89-4140- ext 4501 stephanie.combs@tum.de
Contact: Carmen Kessel, MA +49-89-4140- ext 4501 carmen.kessel@tum.de

Locations
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Germany
Technische Universität München (TUM), Klinikum rechts der Isar Recruiting
Munich, Germany, 81675
Contact: Stephanie E Combs, Prof. Dr.    +49-89-4140- ext 4501    stephanie.combs@tum.de   
Contact: Carmen Kessel, MA    +49-89-4140- ext 4501    carmen.kessel@tum.de   
Sponsors and Collaborators
Stephanie Combs
Investigators
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Principal Investigator: Stephanie E Combs, Prof. Dr. Professor and Department Chair

Publications of Results:
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Responsible Party: Stephanie Combs, Professor and Chair, Technische Universität München
ClinicalTrials.gov Identifier: NCT03288272     History of Changes
Other Study ID Numbers: ERASER
First Posted: September 20, 2017    Key Record Dates
Last Update Posted: September 20, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes