Neratinib in Treating Pediatric Patients with Recurrent or Refractory Solid Tumors or Lymphoma

Inclusion Criteria

• Pathologic confirmation of solid tumor, including central nervous system tumor or lymphoma
• Recurrent or refractory disease for which no further effective standard treatment is available
• Patient must have failed at least one prior therapy
• All patients must have evaluable disease as defined as: * Solid tumors must have a lesion evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 * Central nervous system tumors will be evaluated by Response Assessment in Neuro-Oncology (RANO) criteria
• Available tissue to perform protein and genomic analysis
• Age: * Phase 1: >= 3 and =< 21 years of age at time of enrollment * Phase 2: >= 3 and =< 21 years of age at diagnosis
• Body surface area requirements varied by dose level: * Dose level: -1; body surface area (BSA): >= 0.82 m^2 * Dose level: 1; BSA: >= 0.66 m^2 * Dose level: 2; BSA: >= 0.52 m^2 * Dose level: 3; BSA: >= 0.45 m^2
• Performance level: * Lansky score >= 60% (patients < 16 years of age) * Karnofsky score >= 60% (patients >= 16 years of age)
• Patients must have a shortening fraction >= 27% or left ventricular ejection fraction >= 50% measured by echocardiogram (ECHO) or measured by multiple-gated acquisition scans (MUGA)
• Negative beta-human chorionic gonadotropin (hCG) pregnancy test for female patients of child-bearing potential =< 7 days before starting neratinib therapy
• Female patients of reproductive potential must agree and commit to the use of a highly effective method of contraception, as determined to be acceptable by the investigator, from the time of informed consent until 28 days after the last dose of the investigational product; male patients must agree and commit to use a barrier method of contraception while on treatment and for 3 months after the last dose of the investigational product
• Written informed consent/assent prior to any study-specific procedures
• Patient must be able to swallow tablet or have existing gastrostomy feeding tube to enable administration of tablet
• Patients must have recovered from the acute toxic effects of all prior therapy to =< grade 1 before entering this study

Exclusion Criteria

• Prior treatment within the following timeframes: * Systemic chemotherapy or biologic therapy =< 2 weeks or 5 half lives (t 1/2) of the agent used, whichever is shorter, prior to the start of neratinib * Radiation therapy outside the central nervous system =< 14 days prior to neratinib * Radiation to the central nervous system =< 12 weeks prior to initiation of neratinib
• Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: * =< 60 days from allogeneic SCT * Active acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment for GvHD
• Inadequate marrow function in cohort 1:
• Absolute neutrophil count < 1.0 x 10^9 /L
• Platelets < 100 x 10^9 /L
• Hemoglobin < 8.0 g/dL (transfusion permitted at least 7 days prior to baseline)
• Inadequate liver, renal function as defined below:
• Total bilirubin > 1.5 x the upper limit of normal (ULN) for age
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) > 3 x ULN (unless attributed to disease involvement)
• Serum creatinine > 1.5 x ULN for age or creatinine clearance =< 60 mL/min/1.73 m^2
• Symptomatic or unstable brain metastases; (Note: asymptomatic patients with metastatic brain disease who have been on a stable dose of corticosteroid for treatment of brain metastases for at least 14 days [or decreasing dose of corticosteroid] are eligible to participate in the study); patients with primary central nervous system tumors are eligible
• Clinically active cardiac disease, including prolonged corrected QT (QTc) interval >= 481 ms (i.e. >= grade 2)
• Pregnant or breast-feeding women
• Being actively treated for a concurrent malignancy with the exception of basal cell carcinoma or carcinoma in situ of the cervix
• Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, unexplained fever > 38.5 degree Celsius (C) (101.3 degree Fahrenheit [F]) or psychiatric illness/social situation that would limit compliance with study requirements
• Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or grade >= 2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v.4.0] diarrhea of any etiology at baseline)
• Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related disease
• Known history of hepatitis C or known active hepatitis B infection
• Known hypersensitivity to any component of the investigational product