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Study Summary
No. COGADVL0524:.......Advanced Cancers; Bone; Kidney; Neural; Pediatrics; Sarcoma; Solid Tumors......Winston Huh......Pediatrics
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Study Summary Title
Study Summary
Number:
COGADVL0524
Study Title:Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults with Refractory Solid Tumors
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Physician New Patient Referral
Name:Winston HuhPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:PediatricsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-6620
Contact us about clinical trials
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General Information
Disease Group:Advanced Cancers
Bone
Kidney
Neural
Pediatrics
Sarcoma
Solid Tumors
Supported By:N/A
Phase of Study:Phase IIReturn
Visit:
Evaluations: Prior to each cycle; once between Days 7-14; weekly; post study as
needed.
Treatment
Agents:
BMS-247550
Filgrastim
Ixabepilone
Home Care:Premedications to prevent allergic reactions and Ixabepilone may be given at
home.
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
Optional hospitalization on Days 1-5 of each 21-day cycle; however,
hospitalization may be required, if clinically indicated.
Description/
Intervention:
The goal of this clinical research study is to find out if Ixabepilone can help
to control different types of tumors. The safety of this treatment will be
studied. Researchers will also test a new method (volume analysis) of
measuring changes in the size of tumors in the lungs. Volume analysis measures
the entire volume of a tumor (how much space it takes up) in 3 dimensions
(3-D), instead of the standard method of measuring the longest dimensions of a
tumor (how long or wide it is) in 2 dimensions.
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Study Objectives / Outcomes
1. To determine the response rate to Ixabepilone in various strata of recurrent solid malignant
tumors of childhood and young adulthood. The target tumors are:
a. Embryonal or alveolar rhabdomyosarcoma
b. Osteosarcoma
c. Ewing's sarcoma/Peripheral neuroectodermal tumor (PNET)
d. Synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST)
e. Wilms tumor
f. Neuroblastoma

2. To determine the time to progression for each tumor strata.

3. To prospectively evaluate the feasibility and utility of automated volumetric tumor
measurement in patients with measurable pulmonary metastases, and descriptively
compare volumetric measurements to 1D (RECIST criteria) and 2D (WHO criteria)
measurements.

4. To further define and describe the toxicities of Ixabepilone.
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Study Status Information
Study Activation / Registration Date:01/16/2007
IRB Review and Approval Date:09/06/2006
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Terminated
Projected Accrual:120
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients must be >/= 12 months old at trial entry. Patients with neuroblastoma or Wilms tumor must have been </= 21 years of age when originally diagnosed with the malignancy to be treated on this protocol. All other patients must have been </= 35 years of age when originally diagnosed with the malignancy to be treated on this protocol.

2) All entry/eligibility studies must be performed within 1 week prior to entry onto the trial (unless otherwise specified). Imaging studies are required within 2 weeks of study entry.

3) The date protocol therapy is projected to start must be no later than five calendar days after the date of study enrollment. Patients who are started on protocol therapy on a Phase II study prior to registration will not be entered on study.

4) Patients must have had histologic verification of the malignancy at original diagnosis or at recurrence.

5) The patient must have a histological diagnosis of one of the target tumors: Embryonal or alveolar rhabdomyosarcoma; Osteosarcoma; Ewing's sarcoma/Peripheral neuroectodermal tumor (PNET); Synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST); Wilms tumor; or, Neuroblastoma.

6) All patients must have refractory or recurrent tumors with no known curative treatment options.

7) For patients with sarcoma and Wilms tumor: Patients must have measurable disease. Measurable disease is defined as lesions that can be measured in at least one dimension by medical imaging techniques (CT or MRI scan). Ascites, pleural effusions, bone marrow disease, and lesions detectable only by bone scan will not be considered measurable disease.

8) For patients with neuroblastoma: Patients with either clinically or radiographically measurable disease or evaluable disease by I-MIBG or bone scan are eligible. For evaluable tumor, I-MIBG or bone scan must be positive at a minimum of one site.

9) For patients with neuroblastoma: If the lesion was previously radiated, a biopsy must be done at least 6 weeks after radiation is complete and demonstrate viable neuroblastoma.

10) Patients must have an ECOG performance status of 0, 1 or 2, or Karnofsky >/= 50% (patients > 16 years of age) or Lansky >/= 50% (patients </= 16 years).

11) Patients must have a life expectancy of >/= 8 weeks.

12) Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

13) Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea).

14) Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.

15) XRT: >/= 2 wks for local palliative XRT (small port); >/= 6 months must have elapsed if prior craniospinal XRT or if >/= 50% radiation of pelvis; >/= 6 wks must have elapsed if other substantial BM radiation.

16) Stem Cell Transplant (SCT): No evidence of active graft vs. host disease. For allogeneic SCT, >/= 4 months must have elapsed; for autologous SCT >/= 2 months must have elapsed.

17) Study specific limitations on prior therapy: Patients may not have received prior taxane (paclitaxel, docetaxel) therapy.

18) Concomitant Medications Restrictions: No other cancer chemotherapy, radiation therapy or immunomodulating agents will be used. However, steroids may be used for the treatment and prevention of hypersensitivity reactions and as clinically indicated, for example, for the treatment of pain or chemotherapy associated nausea or vomiting, if necessary.

19) Growth factor(s): Must not have received within 1 week of entry onto this study, with the exception of erythropoietin.

20) Study Specific: Patients may not be currently receiving strong inhibitors of CYP3A4, and may not have received these medications within 1 week of entry.

21) Patients may not be taking enzyme–inducing anticonvulsants, and may not have received these medications within 1 week of entry, as these patients may experience different drug disposition. These medications include: Carbamazepine (Tegretol); Felbamate (Felbtol); Phenobarbital; Phenytoin (Dilantin); Primidone (Mysoline); Oxcarbazepine (Trileptal).

22) All patients must have adequate bone marrow function defined as: Peripheral absolute neutrophil count (ANC) >/= 1500/microL (off growth factors); platelet count >/= 75,000/microL (transfusion independent); and, hemoglobin >/= 8 gm/dL (may receive RBC transfusions).

23) Adequate renal function defined as: Creatinine clearance or radioisotope GFR >/= 70 ml/min/1.73 m^2; OR, 2) maximum serum creatinine (md/dL) based on age/gender as follows: Estimated Creatinine Clearance (in mL/min/1.73 m^2): 1 month to < 6 months: 0.4 md/dL; 6 months to < 1 yr: 0.5 md/dL; 1 to < 2 yrs: 0.6 md/dL; 2 to < 6 yrs: 0.8 md/dL; 6 to < 10 yrs: 1 md/dL; 10 to < 13 yrs: 1.2 md/dL; 13 to < 16 yrs: Male: 1.5 md/dL; Female: 1.4 md/dL; >/= 16 yrs: Male: 1.7 md/dL; Female: 1.4 mg/dL.

24) All patients must have adequate liver function defined As: Total bilirubin </= 1.5 x upper limit of normal (ULN) for age; and SGPT (ALT) </= 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.

25) All patients must have nervous system function defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled. Enzyme inducing anticonvulsant drugs are not allowed on this trial; CNS toxicity </= Grade 2; and, existing sensory or motor neuropathy must be grade </= 1.

26) All patients and/or their parents or legal guardians must sign a written informed consent.

27) All institutional, FDA, and NCI requirements for human studies must be met.

Exclusion Criteria:1) Patients with clinically significant unrelated systemic illness, such as serious infections, hepatic, renal or other organ dysfunction, which would, in the judgment of the treating physician, compromise the patient's ability to tolerate the investigational agent or is likely to interfere with the study procedures or results are excluded.

2) Pregnant or breast-feeding females are excluded, because Ixabepilone may be harmful to the developing fetus or nursing child. Women of child bearing potential must have a negative urine pregnancy test.

3) Patients of child-bearing potential must use appropriate birth control measures.

4) Patients with known severe prior hypersensitivity reaction to agents containing Cremophor EL are excluded.

5) Patients with active brain metastases are excluded.

6) For patients with sarcoma and Wilms tumor: Ascites, pleural effusions, bone marrow disease, and lesions detectable only by bone scan will not be considered measurable disease. Patients who have disease in these locations without radiographically measurable (CT, MRI) disease are excluded.

7) For patients with neuroblastoma: Patients with elevated urinary catecholamines and/or bone marrow evidence of tumor, without measurable or evaluable disease clinically or by imaging modalities (CT, MRI, MIBG, or Bone Scan) are excluded.

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Links
Registration Number: NCT00331643
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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