Neurocognitive Decline in Patients With Brain Metastases

NCT03508752 | Active Not Recruiting Phase 1 DMC FDA Device

• 1 other identifier: STU 122016-064
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline.

Conditions

Brain Metastases

Outcome Measures

Primary Outcomes (2)

• Phase I: To determine the toxicity within 60 days from the date of SRS, in patients with a greater intracranial disease burden, defined as 6 or more metastases.

  Any subject who receives treatment on this protocol will be evaluated for toxicity. Each patient will be assessed for the development of toxicity according to the study calendar. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. The following acute (\<30 days) and subacute (\>30 days - \<60 days) toxicities probably or definitely attributable to the protocol treatment, as defined in CTCAE v5.0, will be dose limiting toxicities (DLT) of the study. Grade 3 or higher neurologic toxicity in the below categories: * Ataxia * Symptomatic Central Nervous System Necrosis which is interfering with ADLs (Activities of Daily Living), or requiring treatment with hyperbaric oxygen, Avastin, or resection. Asymptomatic necrosis present on imaging alone does not constitute DLT. * Cerebral Edema (Grade 4) * Intracranial Hemorrhage * Seizure Any Grade 4 or 5 toxicities definitely attributable to the protocol treatment.

  60 days

• Phase II: Determine the cognitive deterioration (HVLT delayed recall) in patients treated with SRS for multiple metastases (from baseline to 4 months)

  The Hopkins Verbal Learning Test (HVLT) is a memory test that gives information about memory. Each patient will serve as her or his own control, and the relative decline in HVLT-DR (Hopkins Verbal Learning Test- Delayed Recall) score from baseline to 4 month follow-up is defined as Δ HVLT-DR = (HVLT-R DR at baseline - HVLT-DR at 4 month follow up) / HVLT-DR at baseline. A positive change indicates a decline in function.

  4 months

Secondary Outcomes (2)

• Local control

  90 days

• Overall survival (OS)

  2 years

Other Outcomes (16)

• To determine neurocognitive outcomes

  3 years

• To determine the time to distant brain recurrence

  3 years

• To determine the incidence of salvage WBRT or radiosurgery

  4 months

Study Arms (1)

Radiation

EXPERIMENTAL

Stereotactic Radiosurgery

Radiation: Stereotactic Radiosurgery

Interventions

Stereotactic Radiosurgery RADIATION

Stereotactic Radiosurgery dose is based on the largest tumor size

Radiation

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better.
• Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study.
• Six or more metastases on diagnostic or treatment planning imaging, which include either CT Brain (with contrast) or MR Brain (with or without contrast) imaging.
• Largest tumor \<= 4 cm.
• No prior SRS to the lesions which will be treated on protocol.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Prior whole brain radiotherapy
• Patients with life expectancy \< 4 months.
• Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Zabi Wardak, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 22, 2018
• First Posted: April 26, 2018
• Study Start: December 5, 2017
• Primary Completion: April 13, 2026
• Study Completion (Estimated): November 13, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)