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PF-02341066 in Treating Young Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma
This study is not yet open for participant recruitment.
Verified by National Cancer Institute (NCI), July 2009
First Received: July 14, 2009   Last Updated: July 23, 2009   History of Changes
Sponsors and Collaborators: Children's Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00939770
  Purpose

RATIONALE: PF-02341066 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of PF-02341066 and to see how well it works in treating young patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Lymphoma
Neuroblastoma
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: MET tyrosine kinase inhibitor PF-02341066
Other: pharmacogenomic studies
Other: pharmacological study
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I/II Study of PF-02341066, an Oral Small Molecule Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-Met, in Children With Relapsed/Refractory Solid Tumors, Primary CNS Tumors, and Anaplastic Large Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose and recommended phase II dose of MET tyrosine kinase inhibitor PF-02341066 in children with relapsed or refractory solid tumors or anaplastic large cell lymphoma (ALCL) [ Designated as safety issue: Yes ]
  • Toxicities of MET tyrosine kinase inhibitor PF-02341066 [ Designated as safety issue: Yes ]
  • Pharmacokinetics of MET tyrosine kinase inhibitor PF-02341066 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antitumor activity of MET tyrosine kinase inhibitor PF-02341066 in children with relapsed or refractory solid tumors or ALCL [ Designated as safety issue: No ]
  • Antitumor activity of MET tyrosine kinase inhibitor PF-02341066 in children with relapsed or refractory neuroblastoma or ALCL [ Designated as safety issue: No ]
  • Relationship between response to treatment and anaplastic lymphoma kinase gene status in children with relapsed or refractory neuroblastoma or ALCL [ Designated as safety issue: No ]
  • Relationship between minimal residual disease status and clinical response to treatment in children with ALCL [ Designated as safety issue: No ]

Estimated Enrollment: 112
Study Start Date: May 2009
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To estimate the maximum tolerated dose and recommended phase II dose of MET tyrosine kinase inhibitor PF-02341066 administered orally twice daily to children with relapsed or refractory solid tumors or anaplastic large cell lymphoma (ALCL).
  • To define and describe the toxicities of this drug when administered on this schedule.
  • To characterize the pharmacokinetics of this drug in these patients.

Secondary

  • To preliminarily define the antitumor activity of this drug within the confines of a phase I study.
  • To obtain initial phase II data on the antitumor activity of this drug in children with relapsed or refractory neuroblastoma or ALCL.
  • To preliminarily examine the relationship between response to treatment and anaplastic lymphoma kinase gene status (e.g., the presence of a mutation, duplication, amplification, and/or translocation) in children with relapsed or refractory neuroblastoma or ALCL.
  • To preliminarily examine the relationship between minimal residual disease status and clinical response to treatment in children with ALCL.

OUTLINE: This is a multicenter study.

Patients receive oral MET tyrosine kinase inhibitor PF-02341066 twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Plasma and whole blood samples are collected for pharmacokinetic and pharmacogenomic analysis. Tumor tissue (from patients with neuroblastoma) and bone marrow and/or peripheral blood (from patients with anaplastic large cell lymphoma) samples are collected for further correlative laboratory studies.

After completion of study treatment, patients are followed up periodically.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* malignancy at original diagnosis or relapse, including the following:

    • Solid tumors (phase I)
    • CNS tumors (phase I)

      • Neurologic deficits must have been relatively stable for ≥ 1 week before study enrollment
    • Anaplastic large cell lymphoma (ALCL) (phase I or II)

      • No primary cutaneous ALCL
    • Confirmed anaplastic lymphoma kinase (ALK) fusion proteins or ALK mutations (phase I)
    • Neuroblastoma (phase II) NOTE: *Histologic confirmation is not required for patients with diffuse intrinsic brain stem tumors, optic pathway tumors, or pineal region tumors with elevations of serum or CSF tumor markers (e.g., alpha-fetoprotein or beta-HCG).
  • Relapsed or refractory disease
  • Measurable and/or evaluable disease

    • Patients with neuroblastoma must have measurable tumor on MRI, CT scan, or x-ray obtained within the past 2 weeks and/or evaluable tumor by MIBG scan or bone marrow involvement with tumor cells seen on routine morphology
    • Patients with ALCL enrolled in the phase II portion of the trial must have measurable disease
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) or Lansky PS 50-100% (for patients ≤ 16 years of age)

    • Patients who are up in a wheelchair and are unable to walk due to paralysis will be considered ambulatory for the purpose of assessing PS
  • ANC ≥ 1,000/mm^3 (≥ 750/mm^3 in patients with metastatic bone marrow disease)
  • Platelet count ≥ 75,000/mm^3 (transfusion independent, defined as no platelet transfusions within the past 7 days) in patients without bone marrow involvement OR ≥ 25,000/mm^3 (platelet transfusions allowed) in patients with metastatic bone marrow disease
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:

    • ≤ 0.6 mg/dL (for patients 1 year of age)
    • ≤ 0.8 mg/dL (for patients 2 to 5 years of age)
    • ≤ 1.0 mg/dL (for patients 6 to 9 years of age)
    • ≤ 1.2 mg/dL (for patients 10 to 12 years of age)
    • ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
    • ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)
    • ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)
  • Bilirubin (sum of conjugated and unconjugated) ≤ 1.5 times upper limit of normal for age
  • SGPT ≤ 110 U/L
  • Serum albumin ≥ 2 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Body surface area ≥ 0.4 mm² (for patients enrolled at dose levels -1 and 1 only)
  • Able to swallow capsules
  • Able to comply with the safety monitoring requirements of the study, in the opinion of the investigator
  • No uncontrolled infection
  • No evidence of active graft vs host disease
  • Not refractory to red cell or platelet transfusion (in patients with metastatic bone marrow disease)

PRIOR CONCURRENT THERAPY:

  • Recovered from prior chemotherapy, immunotherapy, or radiotherapy
  • No prior MET tyrosine kinase inhibitor PF-02341066
  • At least 6 months since prior total-body radiotherapy (TBI), craniospinal radiotherapy, or radiotherapy to

    • 50% of the pelvis
  • At least 6 weeks since prior therapeutic doses of MIBG
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • At least 2 weeks since prior local palliative radiotherapy (small port)
  • More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) for patients with solid tumors
  • At least 14 days since prior cytotoxic therapy for patients with ALCL who relapse while receiving cytotoxic therapy

    • Patients with lymphoma who relapse during standard maintenance therapy are eligible at time of relapse
    • Cytoreduction with hydroxyurea may be initiated and continued for up to 24 hours before the start of study treatment
  • At least 3 months since prior bone marrow or stem cell transplant or rescue without TBI
  • At least 7 days since prior growth factor therapy
  • At least 7 days since prior biological agents
  • At least 7 days or 3 half-lives (whichever is longer) since prior monoclonal antibody
  • More than 12 days since prior and no concurrent potent CYP3A4 inducers including, but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, or St. John's wort
  • More than 7 days since prior and no concurrent potent CYP3A4 inhibitors including, but not limited to ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, or grapefruit juice
  • No concurrent medications known to be metabolized by CYP3A4 with narrow therapeutic indices, including pimozide, aripiprazole, triazolam, ergotamine, and halofantrine
  • No other concurrent anticancer therapy (including chemotherapy, radiotherapy, immunotherapy, or biologic therapy), except for hydroxyurea for patients with ALCL or decadron for patients with CNS tumors
  • No other concurrent investigational drugs
  • Concurrent corticosteroids for CNS tumors allowed provided the dose has been stable or decreasing for the past 7 days
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00939770

Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Yael P. Mosse, MD Children's Hospital of Philadelphia
  More Information

Additional Information:
No publications provided

Responsible Party: Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital ( Susan M. Blaney )
Study ID Numbers: CDR0000647587, COG-ADVL0912
Study First Received: July 14, 2009
Last Updated: July 23, 2009
ClinicalTrials.gov Identifier: NCT00939770     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific
recurrent neuroblastoma
recurrent childhood anaplastic large cell lymphoma
recurrent childhood brain stem glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
childhood choroid plexus tumor
childhood craniopharyngioma
childhood ependymoblastoma
recurrent childhood medulloblastoma
childhood medulloepithelioma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood ependymoma
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
childhood mixed glioma
childhood oligodendroglioma
recurrent childhood pineoblastoma
recurrent childhood subependymal giant cell astrocytoma
recurrent childhood visual pathway and hypothalamic glioma
childhood central nervous system germ cell tumor
recurrent childhood spinal cord neoplasm
childhood infratentorial ependymoma
childhood supratentorial ependymoma
childhood high-grade cerebellar astrocytoma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebellar astrocytoma
childhood low-grade cerebral astrocytoma
childhood atypical teratoid/rhabdoid tumor

Study placed in the following topic categories:
Choroid Plexus Neoplasms
Rhabdoid Tumor
Neuroectodermal Tumors, Primitive
Tyrosine
Central Nervous System Neoplasms
Neuroblastoma
Ependymoma
Lymphoma, B-Cell
Lymphoma, T-Cell
Neoplasms, Germ Cell and Embryonal
Lymphoma, Large-Cell, Anaplastic
Craniopharyngioma
Neuroepithelioma
Meningioma
Glioma
Lymphoma, Large-cell
Lymphoma
Nervous System Neoplasms
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Astrocytoma
Spinal Cord Neoplasm
Recurrence
Neuroectodermal Tumors
Lymphatic Diseases
Brain Stem Glioma, Childhood
B-cell Lymphomas
Medulloblastoma
Spinal Cord Neoplasms
Oligodendroglioma

Additional relevant MeSH terms:
Lymphoma, Large B-Cell, Diffuse
Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Nerve Tissue
Nervous System Diseases
Central Nervous System Neoplasms
Neuroblastoma
Lymphoma, B-Cell
Neuroectodermal Tumors
Lymphatic Diseases
Neoplasms
Neoplasms by Site
Lymphoma, T-Cell
Neoplasms, Germ Cell and Embryonal
Lymphoma, Large-Cell, Anaplastic
Neoplasms, Neuroepithelial
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Neuroectodermal Tumors, Primitive, Peripheral
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 11, 2009