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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01606878
First received: May 24, 2012
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

This phase I trial studies the side effects and the best dose of crizotinib giving together with combination chemotherapy in treating younger patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma. 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 or by stopping them from dividing


Condition Intervention Phase
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Neuroblastoma
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: crizotinib
Drug: cyclophosphamide
Drug: topotecan hydrochloride
Drug: vincristine sulfate
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Other: pharmacological study
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: questionnaire administration
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of Crizotinib (IND#105573) in Combination With Conventional Chemotherapy for Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • MTD of crizotinib administered with combination chemotherapy based on the incidence of dose-limiting toxicity (DLT) at which fewer than one-third of patients experience DLT, as assessed by NCI CTCAE version 4.0 [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters of crizotinib administered with combination chemotherapy [ Time Frame: Baseline, and at 1, 2, 4, and 6-8 hours post-dose of course 1 ] [ Designated as safety issue: No ]
    The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).


Estimated Enrollment: 58
Study Start Date: March 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A (crizotinib, cyclophosphamide, topotecan hydrochloride)
Patients receive crizotinib PO BID on days 1-21, cyclophosphamide IV QD on days 1-5, topotecan hydrochloride IV QD on days 1-5, and filgrastim or pegfilgrastim beginning on day 6 and continuing until blood count recovers. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Drug: crizotinib
Given orally
Other Names:
  • c-met/hepatocyte growth factor receptor tyrosine kinase inhibitor PF-02341066
  • c-met/HGFR tyrosine kinase inhibitor PF-02341066
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: questionnaire administration
Ancillary studies
Experimental: Part B (crizotinib, vincristine, dexrazoxane, doxorubicin)
Patients receive crizotinib PO BID as in part A. Patients also receive vincristine sulfate IV on day 1, dexrazoxane hydrochloride IV on day 1, doxorubicin hydrochloride IV over 15 minutes on day 1, and filgrastim or pegfilgrastim beginning on day 2 and continuing until blood count recovers. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Drug: crizotinib
Given orally
Other Names:
  • c-met/hepatocyte growth factor receptor tyrosine kinase inhibitor PF-02341066
  • c-met/HGFR tyrosine kinase inhibitor PF-02341066
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexrazoxane hydrochloride
Given IV
Other Names:
  • Cardioxane
  • Savene
  • Totect
  • Zinecard
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: questionnaire administration
Ancillary studies

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Patients must have had histologic verification of malignancy at original diagnosis or relapse; all patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma (ALCL) are eligible except for patients with primary or metastatic central nervous system (CNS) tumors or patients with primary cutaneous ALCL
  • Patients must have either measurable or evaluable disease
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Patients who have a primary or metastatic CNS tumor at the time of study enrollment are not eligible; a prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at study enrollment
  • Karnofsky ≥ 60% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age (patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score)
  • For patients with solid tumors or ALCL without known bone marrow involvement:

    • Peripheral absolute neutrophil count (ANC) ≥ 1,000/mm³
    • Platelet count ≥ 100,000/mm³ (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood count criteria (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min OR a serum creatinine based on age/gender as follows:

    • 0.6 mg/dL (1 to < 2 years of age)
    • 0.8 mg/dL (2 to < 6 years of age)
    • 1.0 mg/dL (6 to < 10 years of age)
    • 1.2 mg/dL (10 to < 13 years of age)
    • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
    • 1.7 mg/dL (male) or 1.4 mg/dL (female) ≥ 16 years of age)
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin ≥ 2 g/dL
  • QTc ≤ 480 msec
  • Shortening fraction of ≥ 27% by echocardiogram or ejection fraction of ≥ 50% by gated radionuclide study
  • Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment
  • Patients must be able to swallow liquid; nasogastric or gastric (G) tube administration is allowed
  • Patients who have an uncontrolled infection are not eligible
  • Patients who, in the opinion of the investigator, may not be able to comply with the safety-monitoring requirements of the study are not eligible
  • See Disease Characteristics
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
  • Solid tumors: At least 21 days since the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
  • ALCL:

    • Patients with ALCL who relapse while receiving standard maintenance chemotherapy will not be required to have a waiting period before enrollment onto this study
    • Patients who relapse while they are not receiving standard maintenance therapy, must have fully recovered from all acute toxic effects of prior therapy; at least 14 days must have elapsed after the completion of cytotoxic therapy
  • At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • At least 42 days since the completion of any type of immunotherapy, e.g., tumor vaccines
  • At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
  • Solid tumors: At least 14 days since prior local palliative radiotherapy (XRT) (small port); ≥ 6 weeks must have elapsed since treatment with therapeutic doses of I^131 iobenguane (MIBG); at least 150 days must have elapsed if prior total-body irradiation (TBI), craniospinal XRT, or ≥ 50% radiation to pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
  • ALCL: At least 14 days after local palliative XRT (small port); at least 84 days must have elapsed if prior TBI, craniospinal XRT, or ≥ 50% radiation to pelvis; at least 42 days must have elapsed if other substantial BM radiation
  • No evidence of active graft-vs-host disease and at least 84 days must have elapsed after stem cell transplant without TBI and ≥ 42 days for autologous stem cell infusion after I^131-MIBG therapy
  • Patients must not have received prior therapy with crizotinib
  • Patients with a total lifetime cumulative anthracycline dose of > 650 mg/m² at the time of enrollment are not eligible for Part B of the study
  • Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anticancer agents including chemotherapy, radiotherapy, immunotherapy, or biologic therapy are not eligible
  • Patients who are receiving cyclosporine, tacrolimus, or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
  • As crizotinib is an inhibitor of cytochrome P450 3A4 (CYP3A4), patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine, and halofantrine are not eligible
  • Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment including, but not limited to, ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible
  • Patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, and St. John wort are not eligible
  • Patients who have received a prior solid organ transplantation are not eligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01606878

Locations
United States, California
Children's Oncology Group
Monrovia, California, United States, 91016
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Emily G. Greengard, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01606878     History of Changes
Other Study ID Numbers: ADVL1212, NCI-2012-01968, U01CA097452
Study First Received: May 24, 2012
Last Updated: August 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Lymphoma, Non-Hodgkin
Lymphoma
Neuroblastoma
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lymphoma, T-Cell
Cyclophosphamide
Liposomal doxorubicin
Doxorubicin
Vincristine
Topotecan
Dexrazoxane
Razoxane
Crizotinib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014