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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

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ClinicalTrials.gov Identifier: NCT02932280
Recruitment Status : Recruiting
First Posted : October 13, 2016
Last Update Posted : December 5, 2017
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

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
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 or Hematologic Malignancies (POE16-01)
Actual Study Start Date : October 2016
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Neratinib

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).




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.



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Ages Eligible for Study:   6 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, or leukemia
  • 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.
    • Leukemia patients must have >10% blasts (or blast equivalent) in the bone marrow
  • Available tissue to perform protein and genomic analysis
  • Age:

    • Phase 1: ≥ 6 and ≤ 21 years of age at time of enrollment
    • Phase 2: ≥ 6 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 therapy with any HER2 directed TKI (e.g., lapatinib, afatinib, dacominib, neratinib, capecitabine) or anti-EGFR antibody therapy (e.g., cetuximab)
  • 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)
  • Inadequate marrow function in Cohort 2

    • These patients will not have marrow function criteria
  • Total bilirubin > 1.5 X the upper limit of normal (ULN) for age
  • AST (SGOT) and ALT (SGPT) > 3 X ULN (unless attributed to leukemia 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02932280


Contacts
Contact: Tanya Trippett, MD 212-639-8267
Contact: Srikanth Ambati, MD 212-639-3964

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: Srikanth Ambati, MD    212-639-3964      
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         
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

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02932280     History of Changes
Other Study ID Numbers: 16-878
First Posted: October 13, 2016    Key Record Dates
Last Update Posted: December 5, 2017
Last Verified: December 2017

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