Whole Brain Radiation Therapy With Boost to Metastatic Tumor Volume Using RapidArc

Sponsor
Emory University (Other)
Overall Status
Completed
CT.gov ID
NCT01218542
Collaborator
(none)
22
Enrollment
2
Locations
1
Arm
116.4
Actual Duration (Months)
11
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Radiation: Volumetric modulated arc therapy
N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Whole Brain Radiation Therapy With Simultaneous Boost to Gross Metastatic Tumor Volume Using Volumetric Modulated Arc Therapy (RapidArc)
Actual Study Start Date :
Sep 22, 2010
Actual Primary Completion Date :
Jun 3, 2020
Actual Study Completion Date :
Jun 3, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Volumetric modulated arc therapy

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.

Radiation: Volumetric modulated arc therapy
Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.

Outcome Measures

Primary Outcome Measures

  1. Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients [Locoregional control at 1 year]

    The cumulative incidences of recurrence locally and in the whole brain were reported at the patient level.

Secondary Outcome Measures

  1. Brain Progression-free Survival [11 months median follow up period.]

    Defined as period of time from study entry to to death from any cause or brain tumor recurrence or progression.

  2. Overall Survival [11 months median follow up period.]

    Defined time from study entry to death from any cause.

  3. Neurocognitive Effects [11 months median follow up period.]

    Neurological test score were assessed using the Hopkins Verbal Learning Test-Revised (HVLT). In the HVLT 12 words are read and the participant is asked to recall them, this is completed 3 times. Total words recalled are summed to give a score for Total Recall (0-36, higher scores demonstrated better recall). Delayed recall is conducted 20-25 minutes later on the same list of 12 words (scored 0-12 with higher scores demonstrating better recall). Retention is calculated as the percent of words recalled (scored 0-100, higher scores representing better recall). Recognition Discrimination is tested by a series of yes/no responses from the participant identifying 12 target words from a list of 24 and calculated by the number of true positives minus the number of true negatives with higher scores indicating a better outcome.

  4. Quality of Life as Measured by the FACT-Br Subscales [11 month median follow up]

    The Functional Assessment of Cancer Therapy-Brain (FACT-Br) were summed to create the FACT brain trial outcome index (FACT-BR TOI), FACT general (FACT-G), and FACT brain total (FACT-BR Total). Three FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient. FACT BR TOTAL (FACT-G + BrCS, possible range 0 - 200) FACT-BR TOI (Trial Outcome Index = Physical Well Being _ Functional Well Being +BrCS, possible range 0 - 148) FACT-G (Fact General, possible range 0 - 108)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Emory University Hospital MidtownAtlantaGeorgiaUnited States30308
2Emory University/Winship Cancer InstituteAtlantaGeorgiaUnited States30322

Sponsors and Collaborators

  • Emory University

Investigators

  • Principal Investigator: Hui-Kuo Shu, MD, PhD, Emory University

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Hui-Kuo Shu, MD, PhD, MD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier:
NCT01218542
Other Study ID Numbers:
  • IRB00045035
  • WCI1784-10
First Posted:
Oct 11, 2010
Last Update Posted:
Jun 29, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Hui-Kuo Shu, MD, PhD, MD, Principal Investigator, Emory University
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment DetailsPatients were recruited at Winship Cancer Institute of Emory University from September 2010 to September 2015.
Pre-assignment Detail
Arm/Group TitleVolumetric Modulated Arc Therapy
Arm/Group DescriptionSingle 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. Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.
Period Title: Overall Study
STARTED22
COMPLETED13
NOT COMPLETED9

Baseline Characteristics

Arm/Group TitleVolumetric Modulated Arc Therapy
Arm/Group DescriptionSingle 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. Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.
Overall Participants22
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
13
59.1%
>=65 years
9
40.9%
Sex: Female, Male (Count of Participants)
Female
13
59.1%
Male
9
40.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
Asian
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
Black or African American
10
45.5%
White
12
54.5%
More than one race
0
0%
Unknown or Not Reported
0
0%
Region of Enrollment (Count of Participants)
United States
22
100%

Outcome Measures

1. Primary Outcome
TitlePercent of Participants With Locoregional Control of Treating Brain Metastasis Patients
DescriptionThe cumulative incidences of recurrence locally and in the whole brain were reported at the patient level.
Time FrameLocoregional control at 1 year

Outcome Measure Data

Analysis Population Description
Feasibility by our criteria was met for all participants.
Arm/Group TitleVolumetric Modulated Arc Therapy
Arm/Group DescriptionSingle 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. Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.
Measure Participants13
1-year Local Control
92
418.2%
Lesion Level Control
98.6
448.2%
1-year Regional Control
46
209.1%
Intracranial Control
46
209.1%
Distant Intracranial Recurrence
87.5
397.7%
2. Secondary Outcome
TitleBrain Progression-free Survival
DescriptionDefined as period of time from study entry to to death from any cause or brain tumor recurrence or progression.
Time Frame11 months median follow up period.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleVolumetric Modulated Arc Therapy
Arm/Group DescriptionSingle 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. Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.
Measure Participants13
Median (Full Range) [months]
5.7
3. Secondary Outcome
TitleOverall Survival
DescriptionDefined time from study entry to death from any cause.
Time Frame11 months median follow up period.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleVolumetric Modulated Arc Therapy
Arm/Group DescriptionThe 2-year neurocognitive effect was not collected. We collected and reported neurocognitive data up to 6 months after treatment.
Measure Participants13
Median (Full Range) [months]
8.6
4. Secondary Outcome
TitleNeurocognitive Effects
DescriptionNeurological test score were assessed using the Hopkins Verbal Learning Test-Revised (HVLT). In the HVLT 12 words are read and the participant is asked to recall them, this is completed 3 times. Total words recalled are summed to give a score for Total Recall (0-36, higher scores demonstrated better recall). Delayed recall is conducted 20-25 minutes later on the same list of 12 words (scored 0-12 with higher scores demonstrating better recall). Retention is calculated as the percent of words recalled (scored 0-100, higher scores representing better recall). Recognition Discrimination is tested by a series of yes/no responses from the participant identifying 12 target words from a list of 24 and calculated by the number of true positives minus the number of true negatives with higher scores indicating a better outcome.
Time Frame11 months median follow up period.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleVolumetric Modulated Arc Therapy
Arm/Group DescriptionSingle 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. Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.
Measure Participants13
Total Recall
1.0
Delayed Recall
1.09
Retention
0.99
Recognition Discrimination
0.96
5. Secondary Outcome
TitleQuality of Life as Measured by the FACT-Br Subscales
DescriptionThe Functional Assessment of Cancer Therapy-Brain (FACT-Br) were summed to create the FACT brain trial outcome index (FACT-BR TOI), FACT general (FACT-G), and FACT brain total (FACT-BR Total). Three FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient. FACT BR TOTAL (FACT-G + BrCS, possible range 0 - 200) FACT-BR TOI (Trial Outcome Index = Physical Well Being _ Functional Well Being +BrCS, possible range 0 - 148) FACT-G (Fact General, possible range 0 - 108)
Time Frame11 month median follow up

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleVolumetric Modulated Arc Therapy
Arm/Group DescriptionSingle 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. Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.
Measure Participants13
FACT-BR Total
1.0
FACT-BR TOI
0.98
FACT-G
0.98

Adverse Events

Time FrameAdverse events were collected thorughout the study assessed up to 2 year follow-up
Adverse Event Reporting Description
Arm/Group TitleVolumetric Modulated Arc Therapy
Arm/Group DescriptionSingle 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. Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.
All Cause Mortality
Volumetric Modulated Arc Therapy
Affected / at Risk (%)# Events
Total10/13 (76.9%)
Serious Adverse Events
Volumetric Modulated Arc Therapy
Affected / at Risk (%)# Events
Total0/13 (0%)
Other (Not Including Serious) Adverse Events
Volumetric Modulated Arc Therapy
Affected / at Risk (%)# Events
Total13/13 (100%)
General disorders
Radiation Necrosis2/13 (15.4%) 2
Fatigue8/13 (61.5%) 8
Nausea5/13 (38.5%) 5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleDr. Hui-Kuo Shu
OrganizationEmory University
Phone404-778-2161
Emailhgshu@emory.edu
Responsible Party:
Hui-Kuo Shu, MD, PhD, MD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier:
NCT01218542
Other Study ID Numbers:
  • IRB00045035
  • WCI1784-10
First Posted:
Oct 11, 2010
Last Update Posted:
Jun 29, 2021
Last Verified:
Jun 1, 2021