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Ixabepilone in Treating Young Patients With Refractory Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00331643
Recruitment Status : Completed
First Posted : May 31, 2006
Last Update Posted : November 14, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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

Condition or disease Intervention/treatment Phase
Adult Rhabdomyosarcoma Adult Synovial Sarcoma Alveolar Childhood Rhabdomyosarcoma Childhood Synovial Sarcoma Embryonal Childhood Rhabdomyosarcoma Previously Treated Childhood Rhabdomyosarcoma Recurrent Adult Soft Tissue Sarcoma Recurrent Childhood Rhabdomyosarcoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Neuroblastoma Recurrent Osteosarcoma Recurrent Wilms Tumor and Other Childhood Kidney Tumors Drug: ixabepilone Phase 2

Detailed Description:


I. 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, and neuroblastoma.

II. Determine the time to progression for each tumor stratum. III. 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.

IV. 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 up every year for 5 years.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults With Refractory Solid Tumors
Study Start Date : April 2006
Actual Primary Completion Date : October 2007
Actual Study Completion Date : June 2009

Arm Intervention/treatment
Experimental: Treatment (ixabepilone)
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.
Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra

Primary Outcome Measures :
  1. Time to progression [ Time Frame: From enrollment until disease progression, death because of treatment complications, resection of measurable tumor or last patient follow-up whichever is first, assessed up to 5 years ]
    Estimated using the product-limit method of Kaplan and Meier.

  2. Progression-free survival (PFS) [ Time Frame: At 6 months ]
    The probability of PFS at 6 months will be summarized.

  3. Response rate (complete response [CR] and partial response [PR]) according to Response Evaluation Criteria in Solid Tumor (RECIST) and World Health Organization (WHO) criteria [ Time Frame: Up to 5 years ]
    Response rates will be calculated as the percent of patients whose best response is a CR or PR, and the fraction of responses obtained will have a 95% confidence interval, which takes into consideration the two-stage nature of the design.

  4. Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 5 years ]
    Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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)
  • Refractory or recurrent disease with no known curative treatment options
  • 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®
  • 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 ofCYP3A4, including any of the following:

    • Clarithromycin
    • Troleandomycin
    • Erythromycin
    • Ketoconazole
    • Itraconazole
    • Fluconazole (doses > 3mg/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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00331643

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United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Brigitte Widemann Children's Oncology Group
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00331643    
Obsolete Identifiers: NCT00318526
Other Study ID Numbers: NCI-2012-01826
NCI-2012-01826 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ADVL0524 ( Other Identifier: Children's Oncology Group )
ADVL0524 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: May 31, 2006    Key Record Dates
Last Update Posted: November 14, 2014
Last Verified: January 2014
Additional relevant MeSH terms:
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Sarcoma, Ewing
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Wilms Tumor
Rhabdomyosarcoma, Embryonal
Neuroectodermal Tumors, Primitive, Peripheral
Sarcoma, Synovial
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases