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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase IBiomarker/Laboratory analysis, TreatmentActive1 to 21NCI, OtherADVL0912
COG-ADVL0912, CDR0000647587, NCT00939770

Trial Description

Summary

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.

Further Study Information

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.

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 mm² (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

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

  • National Cancer Institute
Yael P. Mosse, Study Chair

Trial Sites

U.S.A.

Alabama
Birmingham

Children's Hospital of Alabama at University of Alabama at Birmingham

Alyssa T Reddy
Ph: 205-934-0309

California
Orange

Children's Hospital of Orange County

Ivan I Kirov
Ph: 714-997-3000

San Francisco

UCSF Helen Diller Family Comprehensive Cancer Center

Steven G DuBois
Ph: 877-827-3222

Colorado
Aurora

Children's Hospital Colorado Center for Cancer and Blood Disorders

Lia Gore
Ph: 720-777-6672

District of Columbia
Washington

Children's National Medical Center

Jeffrey S Dome
Ph: 202-884-2549

Georgia
Atlanta

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Cynthia J Wetmore
Ph: 888-785-1112

Illinois
Chicago

Ann and Robert H. Lurie Children's Hospital of Chicago

Stewart Goldman
Ph: 773-880-4562

Indiana
Indianapolis

Riley's Children Cancer Center at Riley Hospital for Children

James M Croop
Ph: 317-274-2552

Massachusetts
Boston

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Suzanne Shusterman
Ph: 866-790-4500

Michigan
Ann Arbor

C.S. Mott Children's Hospital at University of Michigan Medical Center

Rajen Mody
Ph: 800-865-1125

Minnesota
Minneapolis

Masonic Cancer Center at University of Minnesota

Emily G Greengard
Ph: 612-624-2620

Missouri
Saint Louis

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

Robert J Hayashi
Ph: 800-600-3606
Email: info@siteman.wustl.edu

New York
New York

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

Julia Glade-Bender
Ph: 212-305-8615

Ohio
Cincinnati

Cincinnati Children's Hospital Medical Center

John P Perentesis
Ph: 513-636-2799

Columbus

Nationwide Children's Hospital

Mark A Ranalli
Ph: 614-722-2708

Oregon
Portland

Knight Cancer Institute at Oregon Health and Science University

Suman Malempati
Ph: 503-494-1080
Email: trials@ohsu.edu

Pennsylvania
Philadelphia

Children's Hospital of Philadelphia

Elizabeth Fox
Ph: 215-590-2810

Pittsburgh

Children's Hospital of Pittsburgh of UPMC

Jean M Tersak
Ph: 412-692-5573

Tennessee
Memphis

St. Jude Children's Research Hospital

Wayne L Furman
Ph: 866-278-5833
Email: info@stjude.org

Nashville

Vanderbilt-Ingram Cancer Center

Scott C Borinstein
Ph: 800-811-8480

Texas
Dallas

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Naomi J Winick
Ph: 214-648-7097

Houston

Dan L. Duncan Cancer Center at Baylor College of Medicine

Karen R Rabin
Ph: 713-798-1354
Email: burton@bcm.edu

Wisconsin
Milwaukee

Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Michael E Kelly
Ph: 414-805-4380

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00939770
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.