Crizotinib and Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma
Condition: Childhood Solid Neoplasm; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Neuroblastoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Neuroblastoma; Lymphoma, Large-Cell, Anaplastic; Recurrence
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial studies the side effects and the best dose of crizotinib when given
      together with combination chemotherapy in treating younger patients with solid tumors or
      anaplastic large cell lymphoma that has returned or does not respond to treatment. Crizotinib
      may stop the growth of tumor or cancer cells by blocking some of the enzymes needed for cell
      growth. Drugs used in chemotherapy, such as cyclophosphamide, topotecan hydrochloride,
      dexrazoxane hydrochloride, doxorubicin hydrochloride, and vincristine sulfate, work in
      different ways to stop the growth of cancer cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Giving crizotinib together with
      combination chemotherapy may be a better treatment for patients with solid tumors or
      anaplastic large cell lymphoma.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) of
      crizotinib administered orally twice daily in combination with topotecan (topotecan
      hydrochloride) and cyclophosphamide in children with refractory/relapsed solid tumors or
      anaplastic large cell lymphoma (ALCL).

      II. To define and describe the toxicities of crizotinib in combination with topotecan and
      cyclophosphamide administered on this schedule.

      III. To estimate the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) of
      crizotinib administered orally twice daily in combination with vincristine (vincristine
      sulfate) and doxorubicin (doxorubicin hydrochloride)/dexrazoxane (dexrazoxane hydrochloride)
      in children with refractory/relapsed solid tumors or ALCL.

      IV. To define and describe the toxicities of crizotinib in combination with vincristine and
      doxorubicin/dexrazoxane administered on this schedule.

      V. To characterize the pharmacokinetics of crizotinib in children with relapsed/refractory
      cancer when combined with either topotecan and cyclophosphamide or vincristine and
      doxorubicin/dexrazoxane.

      SECONDARY OBJECTIVES:

      I. To preliminarily define the antitumor activity of crizotinib in combination with either
      topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane within the confines
      of a Phase 1 study.

      II. To preliminarily examine the relationship between anaplastic lymphoma kinase (ALK) status
      in patients with neuroblastoma or ALCL and response to crizotinib in combination with either
      topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane.

      III. To preliminarily examine the relationship between minimal residual disease (MRD) status
      and clinical response to crizotinib in combination with either topotecan and cyclophosphamide
      or vincristine and doxorubicin/dexrazoxane in patients with ALCL.

      IV. To use a questionnaire to gather preliminary information on the palatability of the oral
      solution formulation of crizotinib.

      V. To examine ALK and MET proto-oncogene (c-Met) expression, copy number and mutations status
      in archival tumor tissue from solid tumor and ALCL patients.

      VI. To use a questionnaire to gather information on the acceptability of the crizotinib
      capsule formulation.

      OUTLINE: This is a dose-escalation study of crizotinib. Patients are assigned to Part A or
      Part B based on the treating physician's choice and availability of a reservation. After
      closure of Part A and Part B, patients are assigned to Part C.

      PART A (CLOSED TO ACCRUAL 10/3/14): Patients receive crizotinib (oral solution) orally (PO)
      twice daily (BID) on days 1-21, cyclophosphamide intravenously (IV) once daily (QD) on days
      1-5, and topotecan hydrochloride IV QD on days 1-5. Treatment repeats every 21 days for up to
      35 courses in the absence of disease progression or unacceptable toxicity.

      PART B (CLOSED TO ACCRUAL 10/3/14): Patients receive crizotinib (oral solution) PO BID as in
      Part A. Patients also receive vincristine sulfate IV on day 1, dexrazoxane hydrochloride IV
      on day 1, and doxorubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every
      21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

      PART C: Patients receive crizotinib (capsule formulation) PO BID, cyclophosphamide IV QD, and
      topotecan hydrochloride IV QD as in Part A. Treatment repeats every 21 days for up to 35
      courses in the absence of disease progression or unacceptable toxicity.

      PART D: Patients receive crizotinib (microsphere formulation) PO BID, cyclophosphamide IV QD,
      and topotecan hydrochloride IV QD as in Part A. Treatment repeats every 21 days for up to 35
      courses in the absence of disease progression or unacceptable toxicity.
    

Intervention name(s): Crizotinib; Cyclophosphamide; Dexrazoxane Hydrochloride; Doxorubicin Hydrochloride; Laboratory Biomarker Analysis; Pharmacological Study; Questionnaire Administration; Topotecan Hydrochloride; Vincristine Sulfate
Intervention type(s): Drug; Drug; Drug; Drug; Other; Other; Other; Drug; Drug
Intervention description(s): Given PO; Given IV; Given IV; Given IV; Correlative studies; Correlative studies; Ancillary studies; Given IV; Given IV
Other intervention name(s): MET Tyrosine Kinase Inhibitor PF-02341066; PF-02341066; PF-2341066; Xalkori; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Cardioxane; Totect; Zinecard; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; Hycamptamine; Hycamtin; SKF S-104864-A; Topotecan HCl; topotecan hydrochloride (oral); Kyocristine; Leurocristine sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Vincristine; Topotecan; Crizotinib; Dexrazoxane; Razoxane; Tyrosine Protein Kinase Inhibitors
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Crizotinib; Chemotherapy; Solid Tumors; Anaplastic Large Cell Lymphoma