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Official Title

Phase III Trial of Stereotactic Radiosurgery (SRS) Versus Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for Brain Metastases From Small Cell Lung Cancer

Phase
Phase 3
Sponsor
NRG Oncology
Enrollment
200
Timeline
Jun 2021 → Jul 2030
About This Study

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. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Whole brain radiation therapy delivers a low dose of radiation to the entire brain including the normal brain tissue. Hippocampal avoidance during whole-brain radiation therapy (HA-WBRT) decreases the amount of radiation that is delivered to the hippocampus which is a brain structure that is important for memory. The drug, memantine, is also often given with whole brain radiotherapy because it may decrease the risk of side effects related to thinking and memory. Stereotactic radiosurgery may decrease side effects related to memory and thinking compared to standard of care HA-WBRT plus memantine.

Eligibility Criteria

Inclusion Criteria

  • 1Pathologically (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);
  • 2Patients with de novo or recurrent small cell lung cancer are permitted.
  • 3Brain metastases =\< 4 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 prior to study entry.
  • 4The total tumor volume must be 30 cm\^3 or less. Lesion volume will be approximated by measuring the lesion's three perpendicular diameters on contrast enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric measurements via slice by slice contouring on a treatment planning software package can be used to calculate the total tumor volume.
  • 5Brain metastases can be diagnosed synchronous to the initial diagnosis of small cell lung cancer or metachronous to the initial diagnosis and management of small cell lung cancer.
  • 6Brain metastases must be diagnosed on MRI, which will include the following elements:
  • 7REQUIRED MRI ELEMENTS
  • 8Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D) spoiled gradient (SPGR). Acceptable 3D SPGR sequences include magnetization prepared 3D gradient recalled echo (GRE) rapid gradient echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (Brain Volume Imaging) or 3D Fast FE (field echo). The T1-weighted 3D scan should use the smallest possible axial slice thickness, not to exceed 1.5 mm.
  • 9Pre-contrast T1 weighted imaging (3D imaging sequence strongly encouraged).
  • 10A minimum of one axial T2 FLAIR (preferred) or T2 sequence is required. This can be acquired as a two dimensional (2D) or 3D image. If 2D, the images should be obtained in the axial plane.
  • 11ADDITIONAL RECOMMENDATIONS
  • 12Recommendation is that an axial T2 FLAIR (preferred) sequence be performed instead of a T2 sequence.
  • 13Recommendation is that that pre-contrast 3D T1 be performed with the same parameters as the post-contrast 3D T1.
  • 14Recommendation is that imaging be performed on a 3 Tesla (3T) MRI.
  • 15Recommendation is that the study participants be scanned on the same MRI instrument at each time point.
  • 16Recommendation is that if additional sequences are obtained, these should meet the criteria outlined in Kaufmann et al., 2020.
  • 17If additional sequences are obtained, total imaging time should not exceed 60 minutes.
  • 18If additional metastases not known at the time of registration/randomization or seen in the MRI used for eligibility are subsequently found on the radiation therapy (RT) planning MRI such that the total intacranial volume exceeds 30 cm\^3, the patient is still considered eligible.
  • 19History/physical examination
  • 20Age \>= 18
  • 21Karnofsky performance status of \>= 70
  • 22Creatinine clearance \>= 30 ml/min
  • 23Following 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.
  • 24Patients with symptomatic brain metastases and/or brain metastases in eloquent locations (e.g., brainstem, pre-/post central gyrus, visual cortex) are eligible for enrollment on the trial; however, the specific treatment approach of starting with systemic therapy alone and delaying brain radiation is not recommended for these patients.
  • 25Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted.
  • 26Negative 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.
  • 27Patients may have had prior intracranial surgical resection.
  • 28Because neurocognitive testing is the primary goal of this study, patients must be proficient in English or French Canadian.
  • 29The patient must provide study-specific informed consent prior to study entry.
  • 30Patients with impaired decision-making capacity are not permitted on study.
  • 31ELIGIBILITY CRITERIA PRIOR TO STEP 2 REGISTRATION
  • 32The 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.
  • 33NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.
  • 34PRIOR 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 tests 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.
  • 35NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step 1 registration.

Exclusion Criteria

  • 1Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT treatment. Patients may have had prior chemotherapy. Concurrent immunotherapy is permitted.
  • 2For patients receiving fractionated SRS on an every-other-day basis, planned infusion of cytotoxic chemotherapy is not permitted between SRS treatments.
  • 3Brainstem metastasis \> 10 cm\^3
  • 4Prior allergic reaction to memantine.
  • 5Patients with definitive leptomeningeal metastases.
  • 6Known history of demyelinating disease such as multiple sclerosis.
  • 7Contraindication 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).
  • 8Current use of (other N-methyl-D-aspartate \[NMDA\] antagonists) amantadine, ketamine, or dextromethorphan.
  • 9Radiographic 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.
  • 10Mild cases of hydrocephalus not resulting in significant anatomic distortion of the hippocampus are permitted.
  • 11Prior radiotherapy to the brain, including SRS, WBRT, or prophylactic cranial irradiation (PCI).

Locations

223 sites participating in this study

Emory University Hospital Midtown

Atlanta, Georgia 30308

Active, Not Recruiting

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

Active, Not Recruiting

Emory Saint Joseph's Hospital

Atlanta, Georgia 30342

Active, Not Recruiting
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →