Whole Brain Radiotherapy (WBRT) Versus Stereotactic Radiosurgery (SRS) for 4 Upto 10 Brain Metastases

Neoplasm Metastasis Clinical Trial

— WBRTvsSRS  

Official title:

Whole Brain Radiotherapy vs. Stereotactic Radiosurgery for 4 - 10 Brain Metastases:a Phase III Randomized Multicenter Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02353000
• Other study ID #: 01-2015
• Status: Terminated
• Phase: N/A
• Start date: July 2016
• Est. completion date: December 2019

Study information

• Verified date: May 2020
• Source: Maastricht Radiation Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Recently stereotactic radiosurgery (SRS) in 5 up to 10 brain metastases showed to have equal survival as in 2 up to 4 brain metastases. Whole brain radiotherapy (WBRT) is currently the gold standard for patients with more than 3 brain metastases, but has significant side effects. In this prospective randomized phase III trial WBRT is compared to SRS for patients with 4 up to 10 BM.

Description:

Dutch guideline advices stereotactic radiosurgery (SRS) for patients with 1 up to 3 brain metastases (BM) and whole brain radiotherapy (WBRT) for patients with 4 or more BM. The interim analysis from the QUARTZ study showed that WBRT did not provide benefit in quality of life nor survival over best supportive care. WBRT has significant side effects, such as hair loss, fatigue, and cognitive dysfunction which may impair quality of life. A recently published study showed that SRS in patients with 5 up to 10 BM had a comparable survival to patients treated with 2 up to 4 BM. Many systemic therapies do not have a satisfactory intracranial response, because of the blood-brain barrier. The potential advantages of SRS i.e, limiting radiation doses to the uninvolved brain and a high rate of local tumour control by just a single treatment. Next logic step would be to compare WBRT with SRS alone in patients with 4-10 BM and evaluate whether SRS is superior to WBRT with regard to QOL.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: December 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Minimal 4 up to a maximum of 10 BM on diagnostic MRI scan

• Max diameter of single GTV 2.5cm

• Max cumulative GTV of 30cm3

• Karnofsky performance status = 70

• Any solid primary tumour. Small cell lung carcinoma, germinoma, and lymphoma are excluded

• Ability to provide written informed consent

Exclusion Criteria:

• Contra-indication for MRI

• Prior treatment for BM (i.e. surgery, SRS or WBRT)

• Concurrent use of systemic therapy

• Maximum cumulative GTV of more than 30cm3 on planning-MRI

• More than 10 BM on planning-MRI

• A brainstem metastasis with a PTV of more than 20 cm3

Related Conditions & MeSH terms

• Neoplasm Metastasis

Intervention

Radiation:
• Stereotactic Radiosurgery
Stereotactic Radiosurgery for patients with 4 up to 10 brain metastases
• Whole Brain Radiotherapy
Whole Brain Radiotherapy for patients with 4 up to 10 brain metastases

Locations

Country	Name	City	State
Netherlands	AMC	Amsterdam
Netherlands	VUmc	Amsterdam
Netherlands	Haaglanden MC	Den Haag
Netherlands	Maastricht Radiation Oncology (MAASTRO clinic)	Maastricht
Netherlands	Erasmus MC	Rotterdam
Netherlands	Instituut Verbeeten	Tilburg
Netherlands	ZRTI	Vlissingen

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht Radiation Oncology

Country where clinical trial is conducted

Netherlands, 

References & Publications (4)

Gijtenbeek JM, Ho VK, Heesters MA, Lagerwaard FJ, de Graeff A, Boogerd W. [Practice guideline 'Brain metastases' (revision)]. Ned Tijdschr Geneeskd. 2011;155(52):A4141. Review. Dutch. — View Citation

Langley RE, Stephens RJ, Nankivell M, Pugh C, Moore B, Navani N, Wilson P, Faivre-Finn C, Barton R, Parmar MK, Mulvenna PM; QUARTZ Investigators. Interim data from the Medical Research Council QUARTZ Trial: does whole brain radiotherapy affect the surviva — View Citation

Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Taka — View Citation

Zindler JD, Rodrigues G, Haasbeek CJ, De Haan PF, Meijer OW, Slotman BJ, Lagerwaard FJ. The clinical utility of prognostic scoring systems in patients with brain metastases treated with radiosurgery. Radiother Oncol. 2013 Mar;106(3):370-4. doi: 10.1016/j. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Brain salvage during follow-up	Brain salvage during follow-up, type of salvage, and time to salvage after randomisation	1 year
Other	Verbal learning	Verbal recall and verbal regognition is measured using the Hopkins Verbal Learning Test - Revised	Change in verbal recall and verbal recognition from baseline to 3 months after radiotherapy
Other	Quality of life of cancer patients	QoL will be measured using the EORTC QLQ-C30	Change in Quality of life from baseline to 3 months after radiotherapy
Other	Quality of life of cancer patients with brain neoplasms	QoL will be measured using the EORTC QLQ-BN20	Change in Quality of life from baseline to 3 months after radiotherapy
Other	Quality of life of cancer patients measuring cancer-related fatigue	QoL will be measured using the EORTC QLQ-FA13	Change in Quality of life from baseline to 3 months after radiotherapy
Primary	Quality of life in patients with 4 - 10 brain metastases comparing WBRT and SRS	Quality of life is measured by the EQ-5D-5L, a descriptive system of health-related quality of life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression)	Change in quality of life measured from baseline to 3 months after radiotherapy
Secondary	Overall survival steroid use (mg), toxicity including hair loss and fatigue.	Overall survival	1 year
Secondary	Time that patient is functioning independently (Karnofsky = 70)	Time that patient is functioning independently (Karnofsky = 70)	Change in Karnofsky index from baseline to 3 months after radiotherapy
Secondary	Steroid use	Steroid use in mg over time	Change in steroid use from baseline to 3 months after radiotherapy
Secondary	Toxicity measured by hair loss and fatigue	Toxicity measured by hair loss and fatigue using CTCAE version 4.0	Change in toxicity from baseline to 3 months after radiotherapy
Secondary	Degree of independence	Degree of independence of patients using the Barthel index	Change in independence from baseline to 3 months after radiotherapy