Clinical Trial Information:
Protocol – Alliance – A071701
Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.
Pre-Eligibility: Tissue available for biomarker testing (any brain metastasis tissue and extracranial site from any prior resection or biopsy). If the patient does not have any evidence of extracranial disease, or if there is insufficient extracranial tissue for profiling, brain metastasis tissue is sufficient for eligibility.
- Histologic Documentation: Participants must have histologically confirmed parenchymal metastatic disease to the brain from any solid tumor. Note: this includes patients that have controlled extracranial disease with progressive intracranial metastasis, as well as patients that have progressive intracranial and extracranial disease.
New or progressive brain metastases are defined as any one of the following:
- Untreated measurable lesions in patients who have received surgery and/or SRS to one or more other lesions.
- Progressive measurable lesions after radiation, surgery, or prior systemic therapy
- Residual or progressive lesions after surgery if asymptomatic.
- Patients who have had prior WBRT and/or SRS and then whose lesions have progressed by BM-RANO criteria or there are new lesions, are eligible. Lesions treated with SRS may be eligible if there is unequivocal evidence of progression. For patients with NTRK or ROS1 mutations, entrectinib may be used for newly diagnosed brain metastases.
- Patients who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible, but such patients must be asymptomatic or neurologically stable from their CNS metastases.
- Measurable CNS disease (≥ 10 mm).
- Ability to obtain MRIs with contrast.
- No surgery within 2 weeks prior to or after registration. No chemotherapy within 14 days prior to registration.
- For melanoma, patients must have progressed after prior immune checkpoint blockade or for BRAF positive melanoma, BRAF/MEK inhibitors.
- For lung cancer, EGFR mutant patients must have failed EGFR therapies
- For HER2-positive breast cancer patients (regardless of ER/PR status), patients must have received at least one prior HER-2 directed therapy in the metastatic setting.
- For triple negative breast cancer (TNBC), patients must have received at least one chemotherapy in the metastatic setting.
- For ER and/or PR-positive, HER2-negative breast cancer, patients must have received at least one endocrine therapy in the metastatic setting.
- Patients who have received prior treatment with any of the targeted treatments on this study are not eligible for that specific treatment arm(s), but could be eligible for other arms (e.g., a patient who has had prior treatment with abemaciclib would not be eligible for the abemaciclib arm, but could be eligible for another arm).
- Presence of clinically actionable alteration in NTRK, ROS1, or CDK pathway or PI3K pathway in both a brain metastasis and extracranial site per central review.
- No known current diffuse leptomeningeal involvement (diffuse defined as leptomeningeal involvement throughout the CNS axis; if there is documented positive CSF cytology, patient is ineligible).
- Age ≥ 18 years.
- ECOG Performance Status 0-2.
- No uncontrolled medical comorbidities per investigator discretion.
- Radiation to symptomatic non-target sites within neural axis is allowed prior to registration without washout (provided there is at least one untreated target lesion for measurement on study and radiation is completed prior to registration).
- Concurrent systemic corticosteroids are allowed if stable dose of dexamethasone for 7 days prior to registration. Baseline doses and changes in steroid dosing will be captured.
- No concurrent administration of anticancer therapies (except for endocrine therapy or continuation of hormonal therapy or trastuzumab in breast cancer patients). No chemotherapy, targeted therapy or immunotherapy within 14 days prior to entering the study (Note: For abemaciclib arm, a 21-day chemotherapy washout is required.
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug 14 days prior to registration on the study.
- Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.