HF-SRT vs. HS-WBRT in Treating Patients With Brain Oligometastases

Trial Title: HF-SRT vs. HS-WBRT in Treating Patients With Brain Oligometastases

NCT ID: NCT05807165

Condition: Brain Oligometastases

Conditions: Official terms:
Memantine

Conditions: Keywords:
Brain Oligometastases
Stereotactic Radiotherapy (SRT)
Hypofractionation
Hypofractionated Stereotactic Radiotherapy (HF-SRT)
Hippocampus
Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT)
Neurocognitive Functions (NCFs)
Central Nervous System (CNS)
Progression-free Survival (PFS)
CNS Progression-Free Survival (CNS-PFS)
Patterns of CNS Failure

Study type: Observational

Overall status: Not yet recruiting

Study design:

Time perspective: Prospective

Intervention:

Intervention type: Radiation
Intervention name: Hypofractionated Stereotactic Radiotherapy (HF-SRT)
Description: The administered dose-fractionation schemes range between 30 and 35 Gy delivered within two weeks with a dose per fractionation ranging from 6 to 7 Gy.
Arm group label: HF-SRT

Intervention type: Radiation
Intervention name: Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT) plus memantine
Description: - The prescribed dose is 30 Gy delivered in 12 fractions for therapeutic or adjuvant WBRT. - The prescription of memantine for finally twice-daily dosing will be prescribed as follows: - During the first 3 weeks concurrent with the delivery of hippocampus-sparing WBRT, 5-mg morning dose will be initially prescribed [Week 1 -3] - 5-mg twice a day in the following week [Week 4] - A morning dose of 10 mg and an evening dose of 5 mg in the following week [Week 5] - 10-mg twice a day for the subsequent weeks up to Week 24 [Week 6 - 24]
Arm group label: HS-WBRT plus memantine

Summary: [Background] For newly-diagnosed patients with brain metastases (BMs), conventional whole-brain radiotherapy (WBRT) might still remain a common palliative management. However, WBRT-related late consequences, particularly a decline in neurocognitive functions (NCFs), are a major concern. Actually, WBRT-related neurocognitive dysfunction is usually characterized as deterioration involving learning and memory, in which the extremely radiosensitive hippocampus indeed plays a critical role. To postpone the occurrence and mitigate neurocognitive impairments associated with conventional WBRT, there have been some strategies in the clinical practice of radiation oncology. Among them, the technology/technique of highly precise/accurate stereotactic radiosurgery or stereotactic radiotherapy (i.e., hypofractionated stereotactic radiotherapy, HS-SRT) might have been widely administered in irradiating exclusively the focal brain metastatic lesions, particularly in cancer patients with a limited number of brain metastases. By contrast, the planning strategy of hippocampus avoidance during the course of whole-brain irradiation has also been well-established in preserving NCFs. [Methods] Newly-diagnosed cancer patients harboring 1 - 4 brain metastatic lesions are eligible if they still have fair/good performance status. Eligible and enrolled should receive baseline brain MRI examination and pre-WBRT neurocognitive assessment. Although non-randomized, this phase II trial comprises two prospective (radiotherapeutic) cohorts with individually different planning techniques and prescription schedules. Cohort I represents patients referred for arranging partial-brain irradiation; namely, a course of hypofractionated stereotactic radiotherapy (HF-SRT) is delivered within 2 weeks with a cumulative dose of 3000 - 3500 cGy in 5 fractions. By contrast, Cohort II stands for patients referred for arranging the course of hippocampus-sparing WBRT (HS-WBRT), delivered within 3 weeks with a cumulative dose of 3000 cGy in 12 fractions, during which the planning technique of simultaneous integrated boost (SIB) is employed to focally escalate the dose irradiating the brain metastatic foci. Besides, adhering to several international clinical practice guidelines, the synergic use of the neuroprotective agent (memantine) will be routinely applied in the treatment Cohort II (HS-WBRT). In both treatment cohorts, a battery of neuropsychological measures, which includes 7 standardized neuropsychological tests (e.g., executive functions, verbal and non-verbal memory, working memory, and psychomotor speed), is used to evaluate neurocognitive functions. The primary outcome measure is the median time of CNS progression-free survival (CNS-PFS). Secondary outcome measures encompass both neuro-oncological endpoints and neurocognitive endpoints, among which there is cognitive-deterioration-free survival (CD-free survival). CD-free survival is defined mainly as the time from enrollment to a NCF decline of exceeding than 1 SD away from the baseline involving at least one of the assessed NCF tests. Additionally, patients who expire before 6 months or are alive but fail to undergo all the neurocognitive testing administered would also be defined as suffering from cognitive deterioration. [Expected results] This prospective observational study aims to examine thoroughly and analyze the comparatively between the two radiotherapeutic cohorts (HF-SRT versus HS-WBRT), addressing both CNS tumor control and neurocognitive functional outcomes. It is expected that the patterns of (CNS) failure and individual time to progression will be clearly demonstrated in this prospective observational study encompassing two distinct radiotherapeutic cohorts.

Criteria for eligibility:

Study pop:
Patients with newly-diagnosed brain oligometastases and an acceptable performance status would receive baseline neurocognitive assessment.

Sampling method: Non-Probability Sample
Criteria:
Inclusion Criteria: - Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for postoperative adjuvant or therapeutic hypofractionated stereotactic radiotherapy (HF-SRT) - A Fair/good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or an acceptable performance status of Karnofsky Score (KPS) at least 70 - The number and extent of brain metastatic lesions should be no more than three metastatic foci with a greatest diameter no more than 4 cm shown on pre-radiotherapy MRI; namely, that is the clinical setting of oligometastatic brain disease or brain oligometastases Exclusion Criteria: - Patients with their primary cancer arising from hematological malignancies (i.e., malignant lymphomas, leukemia), germ cell tumors, or malignant meningiomas - Patients with MRI-identified metastasis within 5 mm peri-hippocampally - Patients with metastasis involving the brain stem - Clinical suspicion of leptomeningeal spreading - History of prior radiotherapy including stereotactic radiosurgery delivered to brain/head region for any reasons

Gender: All

Minimum age: 20 Years

Maximum age: 85 Years

Locations:

Facility:
Name: Chang Gung Memorial Hospital

Address:
City: Taoyuan
Zip: 333
Country: Taiwan

Start date: August 1, 2023

Completion date: July 31, 2026

Lead sponsor:
Agency: Chang Gung Memorial Hospital
Agency class: Other

Source: Chang Gung Memorial Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05807165