Testing Trametinib as a Potential Targeted Treatment in Cancers With GNAQ or GNA11 Genetic Changes (MATCH-Subprotocol S2)

Prior treatment

• Patients who previously received prior treatment with other MEK inhibitors (including, but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 \[CH4987655\], GDC-0623 and pimasertib) will be excluded

Other illness

• Patients with a history of interstitial lung disease or pneumonitis are excluded
• Patients must not have known hypersensitivity to trametinib or compounds of similar chemical or biologic composition or to dimethyl sulfoxide (DMSO)

Other

• Patients must not have a history or current evidence/risk of retinal vein occlusion (RVO). An eye exam is required at baseline
• Patients with uveal melanoma are excluded

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
• Patients must have GNAQ or GNA11 mutations, or another aberration, as determined via the MATCH Master Protocol
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have NONE of the following cardiac criteria:
  • Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
  • Treatment-refractory hypertension defined as a blood pressure of systolic \> 140 mmHg and/or diastolic \> 90 mmHg which cannot be controlled by anti-hypertensive therapy
• Patients must have an echocardiogram (ECHO) or a nuclear study (multigated acquisition scan \[MUGA\] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) \< the institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be \> 50% for the patient to be eligible
• Patients who previously received monoclonal antibody therapy (e.g., ipilimumab, nivolumab, pembrolizumab and others) must have stopped the prior therapy for 8 or more weeks before starting on trametinib
• Patients with glioblastoma must have histologically or radiographically confirmed recurrent or progressive World Health Organization (WHO) grade 4 glioma (glioblastoma).
  • NOTE: All baseline and post-baseline disease assessments must be performed using contrast-enhanced cranial magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT) for subjects who cannot have MRI performed