Perfexion Brain Metastasis

NCT ID: NCT00805103

Last Updated: 2016-12-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2016-03-31

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.

Conditions

Brain Metastases

Keywords

Brain Metastases; Stereotactic radiosurgery (SRS); Hypofractionated stereotactic radiotherapy (HSRT); Recurrent Brain Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

(HFA-SRT) in Large-Volume Brain Metastases

Group Type: EXPERIMENTAL

Hypofractionated stereotactic radiotherapy

Intervention Type: RADIATION

Patients will be initially administered 8 Gy RT (level). The dose at each level will be increase by 2 Gy up to level 4. If ≥ 2 of the patients in a dose cohort encounter a DLT, then that dose level will be declared the maximum administered dose. An additional 3 patients will then be entered at the previous dose level and provided no more than one patient experiences a DLT, that level will be declared the maximum tolerated dose (MTD). Up to 6 more patients can be treated at the given dose level while awaiting the results of 6 months of follow-up.

Interventions

Hypofractionated stereotactic radiotherapy

Patients will be initially administered 8 Gy RT (level). The dose at each level will be increase by 2 Gy up to level 4. If ≥ 2 of the patients in a dose cohort encounter a DLT, then that dose level will be declared the maximum administered dose. An additional 3 patients will then be entered at the previous dose level and provided no more than one patient experiences a DLT, that level will be declared the maximum tolerated dose (MTD). Up to 6 more patients can be treated at the given dose level while awaiting the results of 6 months of follow-up.

Intervention Type: RADIATION

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Princess Margaret Hospital, Canada

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Caroline Chung, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Princess Margaret Hospital

Locations

University Health Network

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

UHN REB 08-0602-C

Identifier Type: -

Identifier Source: org_study_id