Clinical Trials /

Crizotinib in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma

NCT00939770

Description:

This phase I/II trial the studies side effects and best dose of crizotinib and to see how well it works in treating young patients with solid tumors or anaplastic large cell lymphoma that has returned after a period of improvement or does not respond to treatment. Crizotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. (Phase I completed 2/15/13)

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Malignant Solid Tumor
  • Neuroblastoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Crizotinib</span> in Treating Young Patients With Relapsed or Refractory Solid Tumors or <span class="go-doc-concept go-doc-disease">Anaplastic Large Cell Lymphoma</span>

Title

  • Brief Title: Crizotinib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma
  • 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
  • Clinical Trial IDs

    NCT ID: NCT00939770

    NCT Alias ID: NCT01182896

    ORG ID: ADVL0912

    NCI ID: COG-ADVL0912

    Trial Conditions

    Brain and Central Nervous System Tumors

    Lymphoma

    Neuroblastoma

    Unspecified Childhood Solid Tumor, Protocol Specific

    Trial Interventions

    Drug Synonyms Arms
    crizotinib Treatment (Crizotinib)

    Trial Purpose

    RATIONALE: Crizotinib 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 crizotinib and
    to see how well it works in treating young patients with relapsed or refractory solid tumors
    or anaplastic large cell lymphoma.

    Detailed Description

    OBJECTIVES:

    Primary

    - To estimate the maximum-tolerated dose and recommended phase II dose of crizotinib
    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, phase I dose-escalation study followed by a phase II study.

    Patients receive oral crizotinib twice daily on days 1-28. Treatment repeats every 28 days
    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.

    Trial Arms

    Name Type Description Interventions
    Treatment (Crizotinib) Experimental crizotinib

    Eligibility 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, ALK mutations, or
    ALK amplification (defined as > 4-fold increase in the ALK signal number as
    compared to reference signal number on chromosome 2q arm) (phase I)

    - Neuroblastoma (phase I or 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 and/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 mm (for patients enrolled at dose levels 0 and 1 only)

    - Able to swallow capsules or a liquid suspension/solution

    - 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 crizotinib

    - At least 6 months since prior total-body radiotherapy (TBI), craniospinal
    radiotherapy, or radiotherapy to 50% of the pelvis

    - At least 3 months since prior bone marrow or stem cell transplant (without TBI) ( 6
    weeks for patients with neuroblastoma or patients with confirmed ALK fusion proteins,
    ALK mutations, or ALK amplification)

    - No evidence of active graft-vs-host disease

    - 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 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 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

    Minimum Eligible Age: 1 Year

    Maximum Eligible Age: 21 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum-tolerated dose and recommended phase II dose of crizotinib in children with relapsed or refractory solid tumors or anaplastic large cell lymphoma (ALCL)

    Toxicities of crizotinib

    Pharmacokinetics of crizotinib

    Secondary Outcome Measures

    Antitumor activity of crizotinib in children with relapsed or refractory solid tumors or ALCL

    Antitumor activity of crizotinib in children with relapsed or refractory neuroblastoma or ALCL

    Relationship between response to treatment and anaplastic lymphoma kinase gene status in children with relapsed or refractory neuroblastoma or ALCL

    Relationship between minimal residual disease status and clinical response to treatment in children with ALCL

    Trial Keywords

    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

    recurrent childhood anaplastic astrocytoma

    recurrent childhood anaplastic oligoastrocytoma

    recurrent childhood anaplastic oligodendroglioma

    recurrent childhood fibrillary astrocytoma

    recurrent childhood gemistocytic astrocytoma

    recurrent childhood giant cell glioblastoma

    recurrent childhood glioblastoma

    recurrent childhood gliomatosis cerebri

    recurrent childhood gliosarcoma

    recurrent childhood oligoastrocytoma

    recurrent childhood oligodendroglioma

    recurrent childhood pilocytic astrocytoma

    recurrent childhood pilomyxoid astrocytoma

    recurrent childhood pleomorphic xanthoastrocytoma

    recurrent childhood protoplasmic astrocytoma

    recurrent childhood subependymal giant cell astrocytoma

    recurrent childhood visual pathway and hypothalamic glioma

    recurrent childhood visual pathway glioma

    recurrent childhood medulloblastoma

    recurrent childhood ependymoma

    recurrent childhood pineoblastoma

    recurrent childhood supratentorial primitive neuroectodermal tumor

    childhood choroid plexus tumor

    childhood craniopharyngioma

    childhood ependymoblastoma

    childhood medulloepithelioma

    childhood grade I meningioma

    childhood grade II meningioma

    childhood grade III meningioma

    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