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

Brain Metastasases Clinical Trial

— ERASER  

Official title:

Evaluation of Repeated Whole Brain Radiotherapy Versus Best Supportive Care for Multiple Brain Metastases - the Randomized Trial ERASER.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03288272
• Other study ID #: ERASER
• Status: Recruiting
• Phase: Phase 2
• First received: May 15, 2016
• Last updated: September 16, 2017
• Start date: April 2016
• Est. completion date: May 2018

Study information

• Verified date: September 2017
• Source: Technische Universität München
• Contact: Stephanie E Combs, Prof. Dr.
• Phone: +49-89-4140-
• Email: stephanie.combs[@]tum.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastasases

Intervention

Radiation:
• Whole Brain Radiotherapy
Radiotherapy of the whole brain

Other:
• Best Supportive Care
Best Supportive Care including nutrition, pain medication, steroids as needed

Locations

Country	Name	City	State
Germany	Technische Universität München (TUM), Klinikum rechts der Isar	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Stephanie Combs

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Scharp M, Hauswald H, Bischof M, Debus J, Combs SE. Re-irradiation in the treatment of patients with cerebral metastases of solid tumors: retrospective analysis. Radiat Oncol. 2014 Jan 3;9:4. doi: 10.1186/1748-717X-9-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity	The primary endpoint is toxicity according to CTCAE after whole brain radiotherapy.	3 months
Secondary	loco-regional progression-free survival	follow-up and local control of brain metastases as well as loco-regional control	6 months
Secondary	Quality of Life (QOL)	QOL	6 months
Secondary	Survival	survival after radiotherapy	6 months