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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02932280
Recruitment Status : Recruiting
First Posted : October 13, 2016
Last Update Posted : March 22, 2022
Sponsor:
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

Tracking Information
First Submitted Date  ICMJE October 12, 2016
First Posted Date  ICMJE October 13, 2016
Last Update Posted Date March 22, 2022
Actual Study Start Date  ICMJE October 2016
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 12, 2016)
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.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Dose Finding Study of Neratinib in Children and Young Adults With Cancer That Has Returned or Not Responded to Treatment
Official Title  ICMJE A Phase I/II Study of Neratinib in Pediatric Patients With Relapsed or Refractory Solid Tumors
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Central Nervous System Tumor
  • Lymphoma
  • Leukemia
Intervention  ICMJE 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).
Study Arms  ICMJE 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.
Intervention: Drug: Neratinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 20, 2020)
47
Original Estimated Enrollment  ICMJE
 (submitted: October 12, 2016)
15
Estimated Study Completion Date  ICMJE October 2024
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tanya Trippett, MD 212-639-8267
Contact: Tara O'Donohue, MD 212-639-5557
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02932280
Other Study ID Numbers  ICMJE 16-878
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Memorial Sloan Kettering Cancer Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • 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  ICMJE
Principal Investigator: Tanya Trippett, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP