Clinical trial NCT01046123: Volumetric Modulated Arc Therapy (VMAT) for Brain Metastases
Official title: A Phase II Study of Whole Brain Radiotherapy With Simultaneous Integrated Boost Using Volumetric Modulated Arc Therapy for One to Ten Brain Metastases
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Brain Metastases
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
First posted: 2010-01-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Radiotherapy to the whole brain is standard treatment for cancer that has spread to the brain (brain metastases) as it treats both the metastases that can be seen on scans and the brain metastases that are too small to be seen on scans.

This study will use a novel radiotherapy technique, called volumetric modulated arc therapy (VMAT), to treat patients with brain metastases. This technique allows delivery of both a standard radiation dose to the whole brain as well as a higher radiation dose to the brain metastases at the same time.

The study will assess the effectiveness of using VMAT in treating brain metastases, and examine its potential side-effects.

Detailed description: This is a Phase II prospective clinical trial. Following registration, patients will be required to undertake a baseline questionnaire assessment of daily living activities using the Modified Barthel's index, as well as cognitive assessment using MMSE.

Patients will undergo MRI scan of the brain for radiotherapy planning purposes. During radiotherapy planning and for each of the five radiotherapy fractions, patients will be immobilised in a custom fitted stereotactic mask system, to minimise head movement. During treatment, patients will have daily online setup corrections to ensure treatment accuracy.

Patients will be treated with WBRT/SIB using VMAT, delivering a total of 20 Gy in 5 fractions to the whole brain and 50Gy in 5 fractions to the brain metastases, delivered once daily on working days. Anti-nausea and anti-inflammatory medication will be prescribed to minimise acute toxicity.

Following therapy completion, patients will be seen every 3 months for the 1st year, then every 6 months thereafter. At each clinic visit, clinicians or study investigators will monitor for toxicity from therapy, document neurologic symptoms and signs and performance status as well as Modified Barthel's index and cognitive assessment.

Patients will have contrast-enhanced MRI brain at 3 months and 1 year, and contrast-enhanced CT brain at 6 months and 9 months in the first year and every 6 months after the first year. Serum creatinine levels will be done prior to each scan to ensure safety of intravenous contrast administration.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18
* pathologically confirmed solid malignancy diagnosed within the past 5 years (if the original pathological cancer diagnosis is more than 5 years earlier, a biopsy to confirm metastatic relapse within the past 5 years is required)
* 1-10 brain metastases
* Maximum diameter of largest metastasis ≤ 3 cm
* KPS ≥ 70
* Patient is neurologically stable with or without corticosteroids
* Extracranial disease well-controlled (6-month estimated median life expectancy).
* Available for regular clinical and imaging follow up
* Prior craniotomy permitted

Exclusion Criteria:

* Require craniotomy to relieve mass effect
* Previous cranial radiotherapy
* Metastatic germinoma, small cell carcinoma, multiple myeloma, lymphoma or leukaemia.
* Chemotherapy administered within one week before radiotherapy or planned within one week after radiotherapy.
* Metastases within 0.7 cm of the optic chiasm, brainstem or optic nerves
* Brainstem metastases
* Systemic lupus erythematosis, scleroderma, or other connective tissue disorders not in remission
* Multiple sclerosis
* Glomerular Filtration Rate \< 60 ml/minute
* Non-small cell lung cancer with liver metastases
* Bilirubin \> upper normal limit
* AST or ALT \> 2X upper normal limit
* Pregnancy
* Summed volume of all metastasis PTVs \> 50 cm3

Primary outcomes:
measure: 3 month treatment response of metastases evaluated using contrast-enhanced MRI scan of brain
timeFrame: 3 months post treatment
Secondary outcomes:
measure: 1-year local control of treated metastases evaluated with contrast-enhanced MRI scan of brain
timeFrame: 1 year post-treatment
measure: 1-year brain control of metastases evaluated with contrast-enhanced MRI scan of brain
timeFrame: 1 year post-treatment
measure: Median survival
timeFrame: No time frame
measure: Both acute neurological toxicity (within 3 months of treatment) and late neurological toxicity (beyond 3 months of treatment
timeFrame: 3 months and beyond
measure: Time to decline in activities of daily living evaluated using the Modified Barthel index
timeFrame: No time frame
measure: Time to decline in cognition evaluated with the Mini-mental state examination
timeFrame: No time frame
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver Centre
state: British Columbia
Study officials:
affiliation: British Columbia Cancer Agency
name: Alan M Nichol, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chan M, Ferguson D, Ni Mhurchu E, Yuan R, Gondara L, McKenzie M, Olson R, Thiessen B, Lalani N, Ma R, Nichol A. Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy. Radiat Oncol. 2020 Nov 25;15(1):271. doi: 10.1186/s13014-020-01717-x.
citation: Nichol A, Ma R, Hsu F, Gondara L, Carolan H, Olson R, Schellenberg D, Germain F, Cheung A, Peacock M, Bergman A, Vollans E, Vellani R, McKenzie M. Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study. Int J Radiat Oncol Biol Phys. 2016 Feb 1;94(2):312-21. doi: 10.1016/j.ijrobp.2015.10.017. Epub 2015 Oct 22.