Testing Trametinib as a Potential Targeted Treatment in Cancers With GNAQ or GNA11 Genetic Changes (MATCH-Subprotocol S2)
Condition: Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma
MeSH terms: Lymphoma; Neoplasms; Multiple Myeloma
Intervention: Trametinib Dimethyl Sulfoxide
Intervention description: Given PO
Intervention MeSH terms: Trametinib; Dimethyl Sulfoxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II MATCH treatment trial identifies the effects of trametinib in patients whose
      cancer has genetic changes called GNAQ or GNA11 mutations. Trametinib may block proteins
      called MEK1 and MEK2, which may be needed for cancer cell growth when GNAQ or GNA11 mutations
      are present. Researchers hope to learn if trametinib will shrink this type of cancer or stop
      its growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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)

          -  Patients must not have a history or current evidence/risk of retinal vein occlusion
             (RVO). An eye exam is required at baseline

          -  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

          -  Patients with uveal melanoma are excluded