Clinical trial NCT00805103: Perfexion Brain Metastasis
Official title: Hypofractionated Stereotactic Radiotherapy (HF-SRT) for Large-Volume Brain Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Brain Metastases
Keywords: Brain Metastases
Stereotactic radiosurgery (SRS)
Hypofractionated stereotactic radiotherapy (HSRT)
Recurrent Brain Metastases
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Princess Margaret Hospital, Canada
First posted: 2008-12-09
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Brain metastases occur in 20% to 40% of all patients with cancer , with an incidence 10 times higher than that of primary malignant brain tumors. Patients with brain metastases have a poor prognosis with a median survival of 1-2 months with corticosteroids and 5-7 months with whole brain radiotherapy (WBRT). Local control achieved with WBRT in patients with otherwise controlled systemic disease remains at issue. A single high dose of radiation delivered with high precision to the target lesion (Stereotactic radiosurgery (SRS)), is considered standard care in salvage of recurrent lesions after WBRT. SRS can destroy tumour with very little damage to surrounding tissue. Research suggests that delivering radiotherapy in a number of smaller doses is more beneficial than receiving all of the radiotherapy in a single dose. Brain metastases are well suited for SRS as they are often small, radiographically well-circumscribed, pseudospherical tumors that are noninfiltrative.

Detailed description: With increasing volume of tumor, the dose of radiosurgery that can be safely delivered to recurrent oligo-metastases in the brain must be reduced. However, reducing the dose of radiosurgery also compromises local control. There is mounting evidence of a local control benefit to a hypofractionated approach in radiation delivery for brain metastases compared with single fraction radiosurgery. Here we propose a novel therapeutic strategy that builds on this concept whereby time between each delivered fraction will enable us to measure and adapt to response, with the objective of reducing irradiated volumes and improving outcomes. In general, the treatment of malignant tumors benefits from fractionation of the dose due to a number of radiobiological properties (redistribution, reoxygenation, repair) that distinguish, and select against, malignant lesions in the fractionation process. Hypofractionated stereotactic radiotherapy (HSRT) is a method of delivering a highly conformal dose distribution in a few treatment sessions using a relocatable stereotactic frame. HSRT may be an attractive alternative to SRS because it may 1) improve patient comfort by removing the invasive nature of SRS frames, 2) confer a radiobiologic advantage over single fraction treatment.

Eligibility criteria: Inclusion Criteria:

* 1-5 recurrent brain metastases after WBRT, and
* At least 1 lesions \>2cm in maximum diameter
* ECOG 0-2
* Life expectancy \>3months
* Age ≥ 18 years old

Exclusion Criteria:

* Edentulous patients
* Prior surgery or injury to hard palate
* Severe claustrophobia
* Contraindication to MRI
* Contraindication to IV contrast (Gadolinium) administration
* Other medical conditions that would preclude study investigations
* Prior radiosurgery to recurrent lesions
* Radiation cannot be delivered at the assigned dose level in a manner that respects OAR constraints (3.2.2.4.2.3.4) (e.g. lesions within brainstem or abutting optic structures)
* Any lesion \>5cm in diameter, or total volume of tumor \> 60cc
* Pregnant Women
* Men or women of childbearing potential who are unwilling to employ adequate contraception

Primary outcomes:
measure: This study aims to determine what the maximum tolerated dose of hypofractionated adaptive stereotactic radiotherapy (HFA-SRT) for recurrent brain metastases is.
timeFrame: every 3 months for 3 years
Secondary outcomes:
measure: The secondary outcome will be to evaluate the overall survival and change in tumour response.
timeFrame: every 3 months for 3 years
measure: Measure acute and late toxicities
timeFrame: every 3 months for 3 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Princess Margaret Hospital
name: Caroline Chung, MD
role: PRINCIPAL_INVESTIGATOR
References: