Clinical Trial 23200

• Overview

  Study Title:

  Phase III Trial of Stereotactic Radiosurgery (SRS) versus Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for 10 or fewer Brain Metastases from Small Cell Lung Cancer

  Summary:

  This phase III trial compares the effect of stereotactic radiosurgery to standard of care memantine and whole brain radiation therapy that avoids the hippocampus (the memory zone of the brain) for the treatment of small cell lung cancer that has spread to the brain.

  Objective:

  Primary Objective * Determine whether stereotactic radiosurgery (SRS) relative to whole brain radiotherapy with hippocampal avoidance (HA-WBRT) plus memantine for brain metastases from small cell lung cancer (SCLC) prevents cognitive function failure as measured by cognitive decline on a battery of tests: the Hopkins Verbal Learning Test Revised (HVLT-R), Controled Oral Word Association (COWA) test, and the Trail Making Test (TMT). Secondary Objectives * Determine whether SRS relative to HA-WBRT plus memantine for brain metastases from SCLC preserves cognitive function as separately measured by the HVLT-R, COWA, TMT Parts A and B, and Clinical Trial Battery Composite (CTB COMP). * Assess perceived difficulties in cognitive abilities using PROMIS after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. * Assess symptom burden using the MD Anderson Symptom Inventory for brain tumor (MDASI-BT) after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. * Compare cumulative incidence of intracranial disease progression after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. * Compare overall survival after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. * Compare cumulative incidence of neurologic death after SRS relative to HA-WBRT plus memantine for brain metastases from SCLC. * Compare the number of salvage procedures used to manage recurrent intracranial disease following SRS relative to HA-WBRT plus memantine for SCLC brain metastases. * Compare adverse events between the treatment arms according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. * Compare the risk of developing cerebral necrosis between SRS

• Treatments

  Therapies:

  Radiotherapy; Therapy (NOS)

  Medications:

  memantine ()

• Inclusion Criteria

  Inclusion Criteria:
  • Pathologically (histologically or cytologically) proven diagnosis of small cell lung cancer within 5 years of registration. If the original histologic proof of malignancy is greater than 5 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic or brain metastasis).
  • Ten or fewer brain metastases less than or equal to 3 cm in largest diameter and outside a 5-mm margin around either hippocampus must be visible on contrast-enhanced magnetic resonance imaging (MRI) performed 21 days or less prior to study entry.
  • History/physical examination
  • 18 years of age or older
  • Karnofsky performance status of 70 or greater
  • ollowing the diagnosis of brain metastases, patients can initiate and treat with systemic (chemotherapy and/or immunotherapy) before enrollment only if their brain metastases are asymptomatic and not located in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex). However, within 21 days prior to enrollment, brain MRI must be repeated to confirm eligibility.
  • Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted.
  • Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to registration. Women of childbearing potential and men who are sexually active must use contraception while on study.
  • Patients may have had prior intracranial surgical resection. Patients must have completed prior intracranial surgical resection at least 14 days prior to registration.
  • Because neurocognitive testing is the primary goal of this study, patients must be proficient in English.
  • Patient must provide study-specific informed consent prior to study entry.
  • ELIGIBILITY CRITERIA PRIOR TO STEP 2 REGISTRATION: The following baseline neurocognitive tests must be completed within 21 days prior to Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive test will be uploaded into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business days a notification will be sent via email to the RA to proceed to Step 2.

• Exclusion Criteria

  Exclusion Criteria:
  • Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT treatment. Patients may have had prior chemotherapy. Concurrent immunotherapy is permitted.
  • Prior allergic reaction to memantine.
  • Intractable seizures while on adequate anticonvulsant therapy; more than 1 seizure per month for the past 2 months.
  • Patients with definitive leptomeningeal metastases.
  • Known history of demyelinating disease such as multiple sclerosis.
  • Contraindication to MR imaging such as implanted metal devices that are MRI-incompatible, allergy to MRI contrast that cannot be adequately addressed with pre-contrast medications, or foreign bodies that preclude MRI imaging. (Questions regarding MRI compatibility of implanted objects should be reviewed with the Radiology Department performing the MRI).
  • Current use of (other N-methyl-D-aspartate [NMDA] antagonists) amantadine, ketamine, or dextromethorphan.
  • Radiographic evidence of hydrocephalus or other architectural change of the ventricular system resulting in significant anatomic distortion of the hippocampus, including placement of external ventricular drain or ventriculoperitoneal shunt.
  • Prior radiotherapy to the brain, including SRS, WBRT, or prophylactic cranial irradiation (PCI).
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months.
  • Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of registration.
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
  • Other criteria may apply

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