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

Trial Status: Active

This phase I / II trial studies the side effects and best dose of neratinib and to see how well it works in treating pediatric patients with solid tumors or lymphoma that has come back (recurrent) or has not responded to previous treatment (refractory). Neratinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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


Phoenix Childrens Hospital
Status: ACTIVE
Contact: Jessica Boklan
Phone: 602-933-0920


Little Rock
Arkansas Children's Hospital
Status: ACTIVE
Contact: Kevin James Bielamowicz
Phone: 501-364-1494


Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: ACTIVE
Contact: Norman James Lacayo
Phone: 650-723-5533


Arnold Palmer Hospital for Children
Status: ACTIVE
Contact: Amy Amundson Smith
Phone: 321-841-8588

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Tanya Maria Trippett
Phone: 212-639-8267


Penn State Milton S Hershey Medical Center
Status: ACTIVE
Contact: Valerie Inez Brown
Phone: 717-531-6012


San Antonio
University of Texas Health Science Center at San Antonio
Status: ACTIVE
Contact: Anne-Marie R. Langevin
Phone: 210-567-7460


Salt Lake City
Huntsman Cancer Institute / University of Utah
Contact: Luke Devon Maese
Phone: 801-213-6226


Alberta Children's Hospital
Status: ACTIVE
Contact: Aru Narendran
Phone: 403-210-6418


I. To establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of neratinib in relapsed/refractory pediatric malignancies. (Phase I)

II. To assess the efficacy of neratinib in relapsed/refractory pediatric malignancies at the RP2D. (Phase II)


I. To assess the anti-tumor activity of neratinib in pediatric patients with relapsed/refractory malignancies. (Phase I)

II. To identify the pharmacokinetic profile of neratinib in pediatric patients with relapsed/refractory malignancies. (Phase I)


I. Correlate EGRF, ERBB2 and ERBB4 aberrations with response to neratinib and analyze additional aberrations on the Memorial Sloan Kettering (MSK)-IMPACT platform in the event that there are additional biomarkers that may predict response to neratinib.

II. Correlate expression of ERBB family proteins using immunohistochemistry.

III. Correlate responses by standard analysis (radiology scans or bone marrow analysis) to changes in cell-free tumor deoxyribonucleic acid (DNA).

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive neratinib orally (PO) or through existing feeding tube once a day (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days and then every 12 weeks for up to 12 months.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Tanya Maria Trippett

  • Primary ID 16-878
  • Secondary IDs NCI-2016-01571
  • ID NCT02932280