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Ixabepilone in Treating Young Patients With Refractory Solid Tumors
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Children's Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00331643
  Purpose

RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well ixabepilone works in treating young patients with refractory solid tumors.


Condition Intervention Phase
Kidney Cancer
Neuroblastoma
Sarcoma
Drug: ixabepilone
Phase II

MedlinePlus related topics: Cancer Kidney Cancer Neuroblastoma Soft Tissue Sarcoma
Drug Information available for: Epothilone B Ixabepilone
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults With Refractory Solid Tumors

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

Primary Outcome Measures:
  • Time to progression as measured by the product-limit method of Kaplan-Meier [ Designated as safety issue: No ]
  • Progression-free survival at 6 months [ Designated as safety issue: No ]
  • Response rates (complete response and partial response) [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Correlate tumor burden and change in tumor burden by RECIST, WHO, and volumetric analysis [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: April 2006
Estimated Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the response rate to ixabepilone in various strata of recurrent solid malignant tumors of childhood and young adulthood, including all of the following:

    • Embryonal or alveolar rhabdomyosarcoma
    • Osteosarcoma
    • Ewing's sarcoma/peripheral neuroectodermal tumor
    • Synovial sarcoma or malignant peripheral nerve sheath tumor
    • Wilms' tumor
    • Neuroblastoma
  • Determine the time to progression for each tumor stratum.
  • Prospectively evaluate the feasibility and utility of automated volumetric tumor measurement in patients with measurable pulmonary metastases, and descriptively compare volumetric measurements to 1-dimensional (RECIST criteria) and 2-dimensional (WHO criteria) measurements.
  • Define and describe the toxicities of ixabepilone.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (Ewing's sarcoma/ peripheral neuroectodermal tumor vs osteosarcoma vs alveolar or embryonal rhabdomyosarcoma vs Wilms' tumor vs neuroblastoma vs synovial sarcoma/malignant peripheral nerve sheath tumor).

Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   1 Year to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis (at original diagnosis or recurrence) of 1 of the following:

    • Embryonal or alveolar rhabdomyosarcoma
    • Osteosarcoma*
    • Ewing's sarcoma /peripheral neuroectodermal tumor*
    • Synovial sarcoma or malignant peripheral nerve sheath tumor*
    • Wilms' tumor*

      • Age ≤ 21 years at original diagnosis
    • Neuroblastoma

      • Age ≤ 21 years at original diagnosis
      • Clinically or radiographically measurable or evaluable (by iodine I 123 metaiodobenzoguanine sulfate [^123I-MIBG] or bone scan [evaluable tumors must be positive at ≥ 1 site])

        • If lesion was previously irradiated, a biopsy must be performed ≥ 6 weeks after completion of radiotherapy and viable neuroblastoma must be demonstrated
        • No elevated urinary catecholamines and/or bone marrow evidence of tumor with measurable disease clinically or by imaging modalities (CT scan, MRI, ^123I-MIBG, or bone scan) NOTE: *Measurable disease required; measurable disease is defined as lesions measured in ≥ 1 dimension by CT scan or MRI; ascites, pleural effusions, bone marrow disease, and lesions detectable only by bone scan not considered measurable disease
  • Refractory or recurrent disease with no known curative treatment options

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100% (patients > 16 years of age) OR Lansky PS 50-100% (patients ≤ 16 years)
  • Life expectancy ≥ 8 weeks
  • No evidence of active graft-versus-host disease
  • Absolute neutrophil count ≥ 1,500/mm³ (no growth factors)
  • Platelet count ≥ 75,000/mm³ (transfusion independent)
  • Not pregnant or nursing
  • Fertile patients must agree to use effective contraception
  • Negative pregnancy test
  • Hemoglobin ≥ 8 g/dL (may receive RBC transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 2.5 times ULN
  • No clinically significant unrelated systemic illness that would preclude study treatment, including any of the following:

    • Serious infections
    • Hepatic, renal, or other organ dysfunction
    • CNS toxicity ≤ grade 2
    • No pre-existing sensory or motor neuropathy ≥ grade 2
  • Seizure disorder allowed provided it is well controlled by anticonvulsants
  • No known prior severe hypersensitivity reaction to agents containing Cremophor EL®

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
  • More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks if prior nitrosourea)
  • At least 7 days since prior biologic agents
  • At least 2 weeks since prior local palliative (small-port) radiotherapy
  • At least 6 months since prior craniospinal radiotherapy OR radiotherapy to ≥ 50% of the pelvis
  • At least 6 weeks since other prior substantial bone marrow radiotherapy
  • At least 4 months since prior allogeneic stem cell transplant (SCT)
  • At least 2 months since prior autologous SCT
  • No prior taxane (paclitaxel, docetaxel) therapy
  • More than 1 week since prior growth factor use (except epoetin alfa)
  • More than 1 week since prior and no concurrent strong inhibitors of CYP3A4, including any of the following:

    • Clarithromycin
    • Troleandomycin
    • Erythromycin
    • Ketoconazole
    • Itraconazole
    • Fluconazole (doses > 3 mg/kg/day)
    • Voriconazole
    • Nefazodone
    • Fluvoxamine
    • Verapamil
    • Diltiazem
    • Amiodarone
    • Grapefruit juice
  • More than 1 week since prior and no concurrent enzyme-inducing anticonvulsants, including any of the following:

    • Carbamazepine
    • Felbamate
    • Phenobarbital
    • Phenytoin
    • Primidone
    • Oxcarbazepine
  • No concurrent aprepitant
  • No concurrent Hypericum perforatum (St. John's wort)
  • No concurrent sargramostim (GM-CSF) or interleukin-11
  • No other concurrent chemotherapy or immunomodulating agents
  • No concurrent radiotherapy
  • Concurrent steroids allowed for pain or chemotherapy-associated nausea or vomiting
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00331643

  Show 114 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Brigitte C. Widemann, MD NCI - Pediatric Oncology Branch
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Jacobs S, Fox B, Krailo MD, et al.: Phase II trial of ixabepilone (BMS-247550) in children and young adults with refractory solid tumors: A report from the Children's Oncology Group. [Abstract] J Clin Oncol 26 (Suppl 15): A-10026, 2008.

Study ID Numbers: CDR0000472912, COG-ADVL0524, NCI-06-C-0146, NCI-P6451
Study First Received: May 30, 2006
Last Updated: October 24, 2008
ClinicalTrials.gov Identifier: NCT00331643  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
alveolar childhood rhabdomyosarcoma
childhood synovial sarcoma
embryonal childhood rhabdomyosarcoma
recurrent childhood rhabdomyosarcoma
recurrent childhood soft tissue sarcoma
previously treated childhood rhabdomyosarcoma
recurrent neuroblastoma
recurrent osteosarcoma
recurrent adult soft tissue sarcoma
adult rhabdomyosarcoma
adult synovial sarcoma
recurrent Wilms tumor and other childhood kidney tumors
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor

Study placed in the following topic categories:
Neuroectodermal Tumors, Primitive
Ewing's family of tumors
Malignant mesenchymal tumor
Urogenital Neoplasms
Kidney cancer
Urologic Neoplasms
Osteogenic sarcoma
Neuroblastoma
Soft tissue sarcomas
Sarcoma, Synovial
Neoplasms, Connective and Soft Tissue
Ewing's sarcoma
Sarcoma, Ewing's
Urologic Diseases
Kidney Neoplasms
Neoplasms, Germ Cell and Embryonal
Wilms Tumor
Neuroepithelioma
Kidney Diseases
Rhabdomyosarcoma
Epothilone B
Epothilones
Synovial sarcoma
Wilms' tumor
Osteosarcoma
Renal cancer
Recurrence
Carcinoma
Neuroectodermal Tumors
Peripheral neuroectodermal tumor

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Mitosis Modulators
Tubulin Modulators
Neoplasms, Nerve Tissue
Antimitotic Agents
Neoplasms, Neuroepithelial
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009