Testing Trametinib as a Potential Targeted Treatment in Cancers With NF1 Genetic Changes (MATCH-Subprotocol S1)
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: 50.0
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 a has a genetic change called NF1 mutation. Trametinib blocks proteins called MEK1
      and MEK2, which may be needed for cancer cell growth when an NF1 mutation is 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 deleterious inactivating mutations of NF-1, 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 (eg. 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 spectroscopy (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 MEK inhibitors (including, but not limited to,
             trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623 and
             pimasertib) will be excluded