Comparing 4 approaches for cancer harboring BRAF alterations

Inclusion

• +Adults (≥18 years) with Grade 1-4 glioma or glioneuronal tumor (including glioblastoma, anaplastic astrocytoma, high grade astrocytoma with piloid features, pilocytic astrocytoma, gliosarcoma, anaplastic pleomorphic xanthoastrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, not otherwise specified \[NOS\], ganglioglioma, or recurrent LGG). OR
• +Pediatric patients (8-17 years of age) with a Grade 3 or 4 glioma or glioneuronal tumor, including those with a prior, histologically confirmed, diagnosis of a low-grade glioma or glioneuronal tumor and now have radiographic or histopathological findings consistent with WHO \[2021\] Grade 3 or 4 primary CNS tumor.
• +Participants must have unresectable, locally advanced or metastatic disease that:
• +An archival tissue sample available meeting protocolProtocolThe detailed plan a study must follow.Read more → requirements, or fresh biopsy is required if the archival sample is not available for retrospective confirmation test.
• +Subprotocol A:
• +Male and female, ≥8 years of age, and weighing ≥25 kg.
• +Histologic diagnosis of a solid tumor or primary CNS tumor.
• +Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome) sequencing.
• +Have an archival tissue sample available meeting protocol requirements.
• +ConsentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → to provide scan(s) prior to baselineBaselineYour starting measurements, taken before treatment begins.Read more → to assess change in tumor trajectory.
• +Received all available standard therapy, is intolerant to available therapies, or the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → has determined that treatment with standard therapy is not appropriate.
• +Subprotocol B:
• +Male and female, ≥8 years of age, and weighing ≥25 kg.
• +Histological diagnosis of a primary CNS tumor, including but not limited to the following:
• +ii. Is intolerant to available therapies OR iii. The investigator has determined that treatment with standard therapy is not appropriate.
• +Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test at CLIA or CLIA-equivalent laboratory approved by sponsorSponsorThe organisation responsible for the study overall.Read more → or sponsor-designated central test.
• +Consent to provide scan(s) prior to baseline to assess change in tumor trajectory.
• +Measurable disease based upon specified response criteria, as determined by the radiographic BICR.
• +Participants who are receiving corticosteroid treatment must be on a stable or decreasing dose of ≤8 mg/day of dexamethasone or equivalent corticosteroid treatment for 7 days prior to first dose of study treatments.
• +Subprotocol C:
• +Male and female, ≥8 years of age, and weighing ≥25 kg.
• +Histologic diagnosis of a rare BRAF V600E-mutated solid tumor that is unresectable, locally advanced or metastatic.
• +Measurable disease on CT, MRI, or physical exam
• +Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test.
• +Have an archival tissue sample available meeting protocol requirements.
• +Consent to provide scan(s) prior to baseline to assess change in tumor trajectory
• +Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.
• +Subprotocol D:
• +Male and female, ≥8 years of age, and weighing ≥25 kg.
• +Histologic diagnosis of a solid tumor harboring a BRAF V600E mutation and not eligible for other subprotocols.
• +Measurable disease on CT, MRI, or physical exam.
• +Evidence of BRAF V600E mutation in tumor and/or blood detected by genomic tests.
• +Consent to provide a tumor biopsy.
• +Willingness to comply with the ECG substudy procedures.
• +All adverse eventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline.
• +i. Had prior treatment with radiotherapy and/or first-line chemotherapy or concurrent chemoradiation therapy OR
• +Note: Participants who have a WHO Grade 3 or 4 glioma for whom chemotherapy and/or radiotherapy is not considered standard of careStandard of careThe treatment normally given for a condition outside a study.Read more → may remain eligible for the study.
• +All adverse events related to prior therapies (eg, chemotherapy, radiotherapy, surgery) must have resolved to Grade 1 or baseline.
• +All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline.