Perfexion Brain Metastasis (HF-SRT)

Hypofractionated Stereotactic Radiotherapy (HF-SRT) for Large-Volume Brain Metastases

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.

Study Overview

• Status: Terminated
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Hypofractionated stereotactic radiotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: (HFA-SRT) in Large-Volume Brain Metastases

Radiation: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
This study aims to determine what the maximum tolerated dose of hypofractionated adaptive stereotactic radiotherapy (HFA-SRT) for recurrent brain metastases is.	every 3 months for 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary outcome will be to evaluate the overall survival and change in tumour response.	every 3 months for 3 years
Measure acute and late toxicities	every 3 months for 3 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Princess Margaret Hospital, Canada
• Investigators: Principal Investigator: Caroline Chung, MD, University Health Network, Princess Margaret Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: December 8, 2008
• First Submitted That Met QC Criteria: December 8, 2008
• First Posted (Estimate): December 9, 2008

Study Record Updates

• Last Update Posted (Estimate): December 29, 2016
• Last Update Submitted That Met QC Criteria: December 28, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Brain Metastases; Stereotactic radiosurgery (SRS); Recurrent Brain Metastases; Hypofractionated stereotactic radiotherapy (HSRT)
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Neoplasms, Second Primary
• Other Study ID Numbers: UHN REB 08-0602-C