Safety and Dose Finding Study of Neratinib in Children and Young Adults With Cancer That Has Returned or Not Responded to Treatment

• ClinicalTrials.gov Identifier: NCT02932280
• Recruitment Status: Recruiting
• First Posted: October 13, 2016
• Last Update Posted: March 22, 2023
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Milton S. Hershey Medical Center; M.D. Anderson Cancer Center; Stanford University; Arkansas Children's Hospital Research Institute; Alberta Children's Hospital; Phoenix Children's Hospital; University of Texas
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

Brief Summary:

The purpose of this study is to test the safety of neratinib at different dose levels and to find out what effects, good and bad, it has on the patients and the cancer.

Condition or disease	Intervention/treatment	Phase
Solid Tumor; Central Nervous System Tumor; Lymphoma; Leukemia	Drug: Neratinib	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Neratinib in Pediatric Patients With Relapsed or Refractory Solid Tumors
• Actual Study Start Date: October 2016
• Estimated Primary Completion Date: October 2024
• Estimated Study Completion Date: October 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Neratinib; There are 2 parts to this study: a Phase I part and a Phase II part. The Phase I portion is known as the dose escalation phase where neratinib will be tested in groups of 3-6 patients to establish the maximum tolerated dose (MTD). The phase II portion will determine whether the MTD shows a response to the tumor.	Drug: Neratinib; Neratinib will be administered orally, or through existing gastrostomy feeding tube, once a day with food, preferably in the morning, continuously for 28-day cycles, with no rest between cycles. Dose will be scaled by body surface area (BSA).

Outcome Measures

Primary Outcome Measures :

1. the number of patients who have experienced Dose Limiting Toxicity [ Time Frame: 1 year ]
   NCI CTCAE Version 4.0.Definition of Hematologic Dose-Limiting Toxicity (solid tumor cohort only) Any hematologic toxicity as indicated: Febrile neutropenia defined as Grade 3 or 4 neutropenia with fever ≥ 38.5°C and /or infection requiring antibiotic or antifungal treatment Grade 4 neutropenia lasting > 7 days Grade 4 thrombocytopenia lasting > 7days Any drug-related adverse experience, regardless of grade, leading to a dose reduction of a study drug. Non-Hematologic Dose-Limiting Toxicities: Non-hematologic dose-limiting toxicity will be defined as any Grade 3, 4 or 5 nonhematologic toxicity with the specific exception of: Any grade diarrhea that occurs in the setting of poor compliance with supportive measures that last for < 48 hours Any grade dehydration related to diarrhea that occurs in the setting of inadequate compliance to supportive care measures that last for < 48 hours.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis: 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 RECIST criteria version 1.1;
  • Central nervous system tumors will be evaluated by 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 BSA (m2)

• 1 ≥ 0.82

  1. ≥ 0.66
  2. ≥ 0.52
  3. ≥ 0.45

• Performance level:

  • Lansky score ≥ 60% (patients < 16 years of age)
  • Karnofsky score ≥ 60% (patients ≥ 16 years of age)
• Cardiac Function: 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 β-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 ½) 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)
• Total bilirubin > 1.5 X the upper limit of normal (ULN) for age
• AST (SGOT) and ALT (SGPT) > 3 X ULN (unless attributed to disease involvement)
• Serum creatinine > 1.5 X ULN for age or creatinine clearance ≤ 60mL/min/1.73m^2
• Symptomatic or unstable brain metastases. (Note: Asymptomatic patients with metastatic brain disease who have been on a stable dose of corticosteroids 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 QTc interval ≥ 481ms (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°C (101.3°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

Contacts and Locations

Contacts

Contact: Tanya Trippett, MD; 212-639-8267

Contact: Tara O'Donohue, MD; 212-639-5557

Locations

United States, Arizona

Phoenix Children'S Hospital; Recruiting

Phoenix, Arizona, United States, 85016

Contact: Jessica Boklan, MD 602-546-0920

Principal Investigator: Jessica Boklan, MD

United States, Arkansas

Arkansas Children's Hospital; Recruiting

Little Rock, Arkansas, United States, 72206

Contact: Kathleen Neville, MD, MS 816-364-4405

Principal Investigator: Kathleen Neville, MD, MS

United States, California

Stanford University School of Medicine and Stanford Cancer Institute; Recruiting

Palo Alto, California, United States, 94304

Contact: Norman Lacayo, MD 650-723-5533

Principal Investigator: Norman Lacayo, MD

United States, Florida

Arnold Palmer Hospital for Children; Recruiting

Orlando, Florida, United States, 32806

Contact: Amy Smith, MD 321-841-8588

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Contact: Tanya Trippett, MD 212-639-8267

Contact: Tara O'Donohue, MD 212-639-5557

Principal Investigator: Tanya Trippett, MD

United States, Pennsylvania

Pennsylvania State Hershey Children's Hospital; Recruiting

Hershey, Pennsylvania, United States, 17033

Contact: Valerie Brown, MD. PhD 717-531-6012

United States, Texas

University of Texas; Recruiting

San Antonio, Texas, United States, 78229

Contact: Anne-Marie Langevin, MD 210-743-2300

Principal Investigator: Anne-Marie Langevin, MD

United States, Utah

Huntsman Cancer Institue; Not yet recruiting

Salt Lake City, Utah, United States, 84113

Contact: Luke Maese, DO 801-213-6226

Canada, Alberta

Alberta Children'S Hospital; Recruiting

Calgary, Alberta, Canada, T3B 6A8

Contact: Aru Narendran, MD, PhD 403.210.6418

Principal Investigator: Aru Narendran, MD

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Milton S. Hershey Medical Center

M.D. Anderson Cancer Center

Stanford University

Arkansas Children's Hospital Research Institute

Alberta Children's Hospital

Phoenix Children's Hospital

University of Texas

Investigators

• Principal Investigator: Tanya Trippett, MD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT02932280
• Other Study ID Numbers: 16-878
• First Posted: October 13, 2016
• Last Update Posted: March 22, 2023
• Last Verified: March 2023

Keywords provided by Memorial Sloan Kettering Cancer Center:

Recurrent; Refractory Disease; Neratinib; 16-878

Additional relevant MeSH terms:

Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases