Testing Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A)
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: Binimetinib
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II MATCH treatment trial investigates the good and bad effects of binimetinib in
      patients whose cancer has a genetic change called NRAS mutation. Binimetinib blocks proteins
      called MEK1 and MEK2, which may be needed for cancer cell growth when an NRAS mutation is
      present. Researchers hope to learn if binimetinib 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 NRAS mutation in codon 12, 13, 61 as determined via the MATCH
             Master Protocol

          -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment
             assignment and must have no clinically significant abnormalities in rhythm, conduction
             or morphology of resting ECG (e.g. complete left bundle branch block, third degree
             heart block)

          -  Creatinine =< 1.5 mg/dL, or calculated creatinine clearance (determined as per
             Cockcroft-Gault) >= 50mL/min

          -  Patients must have adequate cardiac function:

               -  Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated
                  acquisition (MUGA) scan or echocardiogram,

               -  QTc interval =< 480 ms

        Exclusion Criteria:

          -  Patients must not have known hypersensitivity to binimetinib or compounds of similar
             chemical or biologic composition

          -  Patients with melanoma are excluded

          -  Patients must not have any active central nervous system (CNS) lesion (i.e., those
             with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases

               -  NOTE: Patients treated with stereotactic radiotherapy or surgery are eligible if
                  the patient remained without evidence of CNS disease progression >= 3 months.
                  Patients must be off corticosteroid therapy for >= 3 weeks

          -  Patients must not have a history or current evidence of retinal vein occlusion (RVO)
             or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension,
             history of hyperviscosity or hypercoagulability syndromes)

          -  Patients must not have a history of retinal degenerative disease

          -  Patients must not have a history of Gilbert's syndrome

          -  Patients must not have uncontrolled arterial hypertension despite medical treatment

          -  Patients must not have active hepatitis B, and/or active hepatitis C infection

          -  Patients must not have neuromuscular disorders that are associated with elevated
             creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic
             lateral sclerosis, spinal muscular atrophy)

          -  Patients must not have impairment of gastrointestinal function or gastrointestinal
             disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea,
             malabsorption syndrome, small bowel resection)

          -  Patients who have received prior MEK inhibitors are excluded