Clinical trial NCT01218542: Whole Brain Radiation Therapy With Boost to Metastatic Tumor Volume Using RapidArc
Official title: Whole Brain Radiation Therapy With Simultaneous Boost to Gross Metastatic Tumor Volume Using Volumetric Modulated Arc Therapy (RapidArc)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neoplasm Metastasis
Keywords: Secondary brain malignancies
RapidArc
Volumetric modulated arc therapy
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2010-10-11
Enrollment: 22
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 are the most common adult intracranial tumor, occurring in approximately 10% to 30% of adult cancer patients, and represent an important cause of morbidity and mortality. The most widely used treatment for patients with multiple brain metastases is whole brain radiation therapy (WBRT). The use of WBRT after resection or stereotactic radiosurgery (SRS) has been proven to be effective in terms of improving local control of brain metastases.

RapidArc (RA) (Varian Medical Systems, Palo Alto, CA) is a new method of delivering radiation that uses "arcs" to deliver highly conformal intensity modulated three dimensional dose distributions. The purpose of this investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis.

Given the limitations of the SRS boost technique, the purpose of our investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis. In this study, we plan to assess the tolerability of using volumetric modulated arc therapy (RapidArc) on patients with brain metastasis to simultaneously treat the entire brain with a concomitant focal boost to grossly identified lesions on MRI scan to try to improve local control and reduce neurocognitive toxicities.

This previous version of this study was a phase I dose escalation trial giving 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease. Prior to this, patients were enrolled onto one of two cohorts with whole brain dose of 30 Gy in 10 fractions with SIB to total of 45 Gy in 10 fractions to gross brain metastatic disease or whole brain dose of 37.5 Gy in 15 fractions with SIB to total of 52.5 Gy in 15 fractions to gross brain metastatic disease. A total of 12 patients have been previously enrolled on this trial. No patients have experienced a dose limiting toxicity (grade 3 or above) at least possibly due to study therapy. Also, no patients experienced local brain failure/progression at a site of treated metastatic brain disease. Based on this, we no longer feel that dose escalation to the gross brain disease is warranted and would proceed with a single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.


Eligibility criteria: Inclusion Criteria:

* Pathologic proven diagnosis of solid tumor malignancy.
* Age ≥ 18.
* KPS ≥ 70.
* Mini Mental Status Exam (MMSE) ≥ 18 prior to study entry.
* RPA class I (KPS ≥ 70, primary cancer controlled, age \< 65, metastases in brain only) or class II (lack of one or more of class I criteria).
* One to ten brain metastatic lesions.

Exclusion Criteria:

* Previous whole brain radiation therapy.
* Previous radiosurgery to any currently progressive gross metastatic disease.
* Previous radiosurgery to any intracranial site within the prior 6 weeks.
* Recursive partitioning analysis (RPA) class III (KPS \< 70).
* Radiosensitive (eg. small cell lung carcinomas, germ cell tumors, leukemias, or lymphomas) or unknown tumor histologies.
* Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation).
* Evidence of leptomeningeal disease by MRI and/or cerebrospinal fluid (CSF) cytology.
* Current pregnancy.
* No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm).

Primary outcomes:
measure: Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients
timeFrame: Locoregional control at 1 year
Secondary outcomes:
measure: Brain Progression-free Survival
timeFrame: 11 months median follow up period.
measure: Overall Survival
timeFrame: 11 months median follow up period.
measure: Neurocognitive Effects
timeFrame: 11 months median follow up period.
measure: Quality of Life as Measured by the FACT-Br Subscales
timeFrame: 11 month median follow up
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University
name: Hui-Kuo Shu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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citation: Zhong J, Waldman AD, Kandula S, Eaton BR, Prabhu RS, Huff SB, Shu HG. Outcomes of whole-brain radiation with simultaneous in-field boost (SIB) for the treatment of brain metastases. J Neurooncol. 2020 Mar;147(1):117-123. doi: 10.1007/s11060-020-03405-y. Epub 2020 Jan 22.