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Ixabepilone in Treating Young Patients With Refractory Solid Tumors
This study has been completed.
First Received: May 30, 2006   Last Updated: August 27, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: 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

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

Resource links provided by NLM:


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
Primary Completion Date: January 2009 (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

  Hide Study Locations
Locations
United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital Central California
Madera, California, United States, 93638-8762
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States, 90801
Children's Hospital of Orange County
Orange, California, United States, 92868
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123-4282
Southern California Permanente Medical Group
Downey, California, United States, 90242-2814
Stanford Cancer Center - Stanford
Stanford, California, United States, 94305-5824
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Connecticut
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut, United States, 06360-2875
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
All Children's Hospital
St. Petersburg, Florida, United States, 33701
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States, 33176
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Nemours Children's Clinic - Orlando
Orlando, Florida, United States, 32806
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States, 32504
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 96813
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62794-9620
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
United States, Kentucky
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0293
United States, Louisiana
Tulane Cancer Center Office of Clinical Research
Alexandria, Louisiana, United States, 71315-3198
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Floating Hospital for Children at Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Breslin Cancer Center at Ingham Regional Medical Center
Lansing, Michigan, United States, 48910
Spectrum Health Hospital - Butterworth Campus
Grand Rapids, Michigan, United States, 49503-2560
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
United States, Minnesota
University of Minnesota Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
United States, Mississippi
University of Mississippi Cancer Clinic
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Siteman Cancer Center at Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, Nevada
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States, 89109-2306
United States, New Jersey
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Overlook Hospital
Morristown, New Jersey, United States, 07962
United States, New Mexico
University of New Mexico Cancer Research and Treatment Center
Albuquerque, New Mexico, United States, 87131-5636
United States, New York
Memorial Sloan - Kettering Cancer Center
New York, New York, United States, 10021-6094
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Leo W. Jenkins Cancer Center at ECU Medical School
Greenville, North Carolina, United States, 27835-6028
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Tod Children's Hospital
Youngstown, Ohio, United States, 44501
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Legacy Emanuel Hospital and Health Center & Children's Hospital
Portland, Oregon, United States, 97227
Oregon Health & Science University Cancer Institute
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-0001
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-9786
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
United States, Rhode Island
Rhode Island Hospital Comprehensive Cancer Center
Providence, Rhode Island, United States, 02903
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Palmetto Health South Carolina Cancer Center
Columbia, South Carolina, United States, 29203
United States, Tennessee
T.C. Thompson Children's Hospital
Chattanooga, Tennessee, United States, 37403
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37901
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
United States, Texas
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030-2399
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229-3993
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Texas Tech University Health Sciences Center School of Medicine - Amarillo
Amarillo, Texas, United States, 79106
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78207
United States, Virginia
INOVA Fairfax Hospital
Falls Church, Virginia, United States, 22042-3300
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, United States, 99220-2555
United States, West Virginia
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
Huntington, West Virginia, United States, 25701
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
Charleston, West Virginia, United States, 25302
United States, Wisconsin
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Australia, New South Wales
Westmead Institute for Cancer Research at Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Royal Children's Hospital
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada
Centre Hospitalier Universitaire de Quebec
Quebec, Canada, G1V 4G2
Canada, British Columbia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3K 6R8
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 3N6
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Children's Hospital of Western Ontario
London, Ontario, Canada, N6A 4G5
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
New Zealand
Christchurch Hospital
Christchurch, New Zealand
Wellington Children's Hospital
Wellington, New Zealand, 6002
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Brigitte C. Widemann, MD NCI - Pediatric Oncology Branch
  More Information

Additional Information:
Publications:
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.

Responsible Party: Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers: CDR0000472912, COG-ADVL0524, NCI-06-C-0146, NCI-P6451
Study First Received: May 30, 2006
Last Updated: August 27, 2009
ClinicalTrials.gov Identifier: NCT00331643     History of Changes
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

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Urogenital Neoplasms
Urologic Neoplasms
Neuroblastoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Kidney Diseases
Neoplasms by Histologic Type
Epothilones
Mitosis Modulators
Antimitotic Agents
Pharmacologic Actions
Carcinoma
Neuroectodermal Tumors
Neoplasms
Tubulin Modulators
Sarcoma
Carcinoma, Renal Cell
Adenocarcinoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 30, 2009