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

NCT03189381 | Terminated Results DMC FDA Device

• 1 other identifier: IUSCC-0605
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

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.

Conditions

Brain Metastases

Keywords

Whole Brain Radiation; Simultaneous Integrated Boost

Outcome Measures

Primary Outcomes (1)

• In-Brain Distant Failure Rate

  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). This is the binomial proportion of patients who experienced in-brain distant failure by 6 months and the associated 95% confidence interval.

  6 Months

Secondary Outcomes (8)

• Treated Lesion Local Control

  6 Months

• Overall Survival for Evaluable Patients

  6 Months

• Change in Neurocognitive Function From Baseline to 6 Months

  6 Months

• Change in Health-Related Quality of Life (QoL) From Baseline to 6 Months

  6 Months

• Change in Performance Status

  12 Months

Study Arms (2)

Cohort A

EXPERIMENTAL

Standard PCI dose

Radiation: Cohort A

Cohort B

EXPERIMENTAL

Low PCI dose

Radiation: Cohort B

Interventions

Cohort A RADIATION

Cohort A - WBRT dose = 25 Gy, SIB dose = 42 Gy, # of daily fractions = 10, SIB dose in EQD2 = 49.7 Gy

Cohort A

Cohort B RADIATION

Cohort B - WBRT dose = 20 Gy, SIB dose = 40 Gy, # of daily fractions = 8, SIB dose in EQD2 = 50.0 Gy

Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 at time of consent.
• Ability to provide written informed consent and HIPAA authorization.
• Pathological diagnosis of any solid tumor histology (from any site in the body).
• Pathological or clinical (i.e., by imaging) diagnosis of brain metastatic tumor lesions.
• Total volume of lesions ≤ 30 cm3.
• 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.
• Not a candidate for or eligible for but refused Gamma Knife radiosurgery.

You may not qualify if:

• Previous radiation to the brain, including WBRT or brain radiosurgery.
• Life expectancy \< 6 months (as estimated per current ds-GPA).
• For histologies not included in the ds-GPA publications or otherwise noted online at brainmetgpa.com, the PI will use either published or validated data, or the PI's best clinical judgment to determine the patient's expected survival.
• Inability to comply with treatment per investigator discretion.
• Inability to complete neurocognitive assessments per investigator discretion.

Sponsors & Collaborators

• Indiana University: lead

Study Sites (3)

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Early termination leading to no patients enrolled in cohort B.

Results Point of Contact

• Title: Dr. Kevin Shiue
• Organization: Indiana University (IU)

kshiue@iupui.edu

317 944 2524

Study Officials

• Kevin R. Shiue, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 16, 2017
• Study Start: September 21, 2017
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: June 28, 2024
• Results First Posted: June 28, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)