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Pilot Phase 2 Study Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03189381
Recruitment Status : Recruiting
First Posted : June 16, 2017
Last Update Posted : April 25, 2019
Sponsor:
Information provided by (Responsible Party):
Gordon A Watson, MD/PhD, Indiana University

Brief Summary:

This trial is a pilot, Phase 2, sequential two-cohort study designed to test two de-escalated whole brain radiation therapy (WBRT) dose levels and assess their ability to maintain acceptable in-brain distant control. The WBRT dose would decrease as the study moves forward, both in terms of absolute value and equivalent dose in 2 Gray fractions (EQD2) (as determined by the linear quadratic radiobiological model). The absolute value of the simultaneous integrated boost (SIB) dose will change with each dose level because the number of fractions delivered will depend on the WBRT dose. As such, the SIB dose will be manipulated such that the EQD2 will remain essentially equivalent despite the difference in the number of fractions delivered. This design will ensure that the only variable is the change in WBRT dose.

The concept is that WBRT with SIB would be expected to maximize both local and in-brain distant control as has already been shown in studies exploring WBRT with SRS boost. However, by itself WBRT with SIB does not address the concern over neurocognitive outcomes. Therefore, investigators hypothesize that there is a lower WBRT dose threshold that will maintain acceptable in-brain distant control, particularly in the setting of a SIB to gross lesions to maintain treated lesion control. In addition, lower overall brain dose (including lower hippocampal dose without specific hippocampal avoidance) may potentially improve neurocognitive function. Investigators are also interested in evaluating treated lesion control, overall survival, neurocognitive sequelae of therapy, quality of life, performance status, and adverse effects of therapy. Biomarker identification for potential correlative circulating tumor DNA and microRNA is an exploratory endpoint to generate data for future prospective evaluation.


Condition or disease Intervention/treatment Phase
Brain Metastases Radiation: Cohort A Radiation: Cohort B Phase 2

Detailed Description:

Primary Objective Evaluate two de-escalated whole brain radiation dose levels (in the setting of simultaneous integrated boost to gross lesions) with respect to in-brain distant control for brain metastases, defined as an in-brain failure rate outside of the planning target volume at 6 months of < 20%.

Secondary Objectives

  1. Evaluate treated lesion control at 6 months for brain metastases in the setting of a predetermined total biologically effective SIB dose as determined by radiographic progression within the planning target volume with fusion and overlay of follow-up MRIs.
  2. Evaluate overall survival at 6 months for brain metastases in the setting of WBRT with SIB.
  3. Evaluate changes in neurocognitive function after WBRT with SIB in the following domains: verbal learning and memory as assessed by the Hopkins Verbal Learning Test - Revised (HVLT-R); memory, executive function, and higher order cognition as assessed by the Groton Maze Learning Test; and working memory via either the Two Back Test or One Back Test (depending on patient performance at baseline). All tests except the HVLT-R are part of a custom battery designed with the help of CogState psychology staff and will be delivered via the CogState platform.
  4. Evaluate changes in health-related quality of life as assessed by the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-Br) after WBRT-SIB for brain metastases.
  5. Evaluate changes in performance status as assessed by the Karnofsky Performance Status tool after WBRT-SIB for brain metastases.
  6. Evaluate adverse events after WBRT-SIB for brain metastases according to current CTCAE criteria and documented by the LENT-SOMA form.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Phase 2 Study Evaluating Dose De-escalation in Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases
Actual Study Start Date : July 6, 2017
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2021

Arm Intervention/treatment
Experimental: Cohort A
Standard PCI dose
Radiation: Cohort A
Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy

Experimental: Cohort B
Low PCI dose
Radiation: Cohort B
Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy




Primary Outcome Measures :
  1. In-brain distant failure rate [ Time Frame: 6 months ]
    An actuarial 6-month rate of new parenchymal lesions seen outside the planning target volume of any lesion that received SIB on any post-treatment MRI (in all 3 planes)


Secondary Outcome Measures :
  1. Treated lesion control [ Time Frame: 6 months ]
    An actuarial 6-month rate of any new, recurrent, or progressing (as defined by Response Assessment in Neuro-Oncology Brain Metastases criteria) tumor within the planning target volume on any post-treatment MRI

  2. Overall survival [ Time Frame: 6 months ]
    An actuarial 6-month rate of patients still alive regardless of disease status

  3. Change in neurocognitive function [ Time Frame: 6 months ]
    Total change in score of neurocognitive tests (Hopkins Verbal Learning Test - Revised, Groton Maze, and Two or One Back Test)

  4. Change in health-related quality of life [ Time Frame: 6 months ]
    Total change in score of health-related quality of life test (Functional Assessment of Cancer Therapy with Brain Subscale)

  5. Change in performance status [ Time Frame: 6 months ]
    Total change in performance status score (Karnofsky)

  6. Incidence of early and late adverse effects [ Time Frame: 1 year ]
    Adverse effects will be defined per CTCAE



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age ≥ 18 at time of consent.
  2. Ability to provide written informed consent and HIPAA authorization.
  3. Pathological diagnosis of any solid tumor histology (from any site in the body).
  4. Pathological or clinical (i.e., by imaging) diagnosis of brain metastatic tumor lesions.
  5. Total volume of lesions ≤ 30 cm3.
  6. Maximum volume of largest lesion ≤ 5 cm3.

    a. This volume limit would be equivalent to a largest diameter of about 2.1 cm, assuming a perfect sphere.

  7. Not a candidate for or eligible for but refused Gamma Knife radiosurgery.

Exclusion Criteria

  1. Previous radiation to the brain, including WBRT or brain radiosurgery.
  2. Life expectancy < 6 months (as estimated per ds-GPA).
  3. Inability to comply with treatment per investigator discretion.
  4. Inability to complete neurocognitive assessments per investigator discretion.

Of note, tumor lesion number is not an inclusion or exclusion criteria as we are using volume-based criteria instead.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03189381


Contacts
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Contact: Kathy Lauer 317-962-3172 klauer@iuhealth.org

Locations
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United States, Indiana
Indiana University Health Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Kathy Lauer    317-962-3172    klauer@iuhealth.org   
Principal Investigator: Gordon A. Watson, MD, PhD         
Indiana University Health Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Kathy Lauer    317-962-3172    klauer@iuhealth.org   
Principal Investigator: Gordon A. Watson, MD, PhD         
Methodist Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Kathy Lauer    317-962-3172    klauer@iuhealth.org   
Principal Investigator: Gordon A. Watson, MD, PhD         
Sponsors and Collaborators
Indiana University
Investigators
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Principal Investigator: Gordon A. Watson, MD, PhD Indiana University School of Medicine

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Responsible Party: Gordon A Watson, MD/PhD, Associate Professor, Indiana University
ClinicalTrials.gov Identifier: NCT03189381    
Other Study ID Numbers: IUSCC-0605
First Posted: June 16, 2017    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gordon A Watson, MD/PhD, Indiana University:
Whole Brain Radiation
Simultaneous Integrated Boost
Additional relevant MeSH terms:
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Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases