Background:

-Ixabepilone is a
member of a new class of anticancer drugs called epothilones, which
interfere with the ability of cancer cells to divide. Ixabepilone kills
cancer cells in the test tube and in animals.

-Epothilones are
similar to a class of drugs called taxanes, which include Taxol®
(Registered Trademark) (paclitaxel) and Taxotere® (Registered
Trademark) (docetaxel). Epothilones can kill cancer cells that are
resistant to Taxol® (Registered Trademark) in the laboratory.

-Ixabepilone has been
tested in a small number of adults and children with cancers resistant
to standard treatment.

Objectives:

-To measure the
response of solid tumors to treatment with ixabepilone.

-To determine for how
long ixabepilone can stop tumors from growing.

-To evaluate a new
method of measuring tumors in the chest with a method that measures
tumor volume.

-To further define the
side effects of ixabepilone.

Eligibility:

-Patients with
osteosarcoma, Ewing's sarcoma/peripheral neuroectodermal tumor,
rhabdomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath
tumor, neuroblastoma, or Wilms tumor.

-Patients must be 12
months or older when entering the study.

-Patients with sarcoma
must have been no more than 35 years old at the time of diagnosis.

-Patients with Wilms
tumor or neuroblastoma must have been no more than 21 years old at the
time of diagnosis.

Design:

-Up to 20 patients
with each type of tumor may be enrolled.

-Patients are given
ixabepilone as a 1-hour infusion through a vein on days 1-5 of every
21-day cycle.

-Patients have a
physical exam and urine test before each cycle, blood tests weekly,
pregnancy test (for women who can bear children) every other cycle, and
tests to evaluate the tumor (radiological, imaging, or others,
depending on the tumor type) after the first cycle and then after every
other cycle.

-Patients may continue
treatment as long as their tumor responds to therapy and the side
effects are not unacceptable.

Condition	Intervention	Phase
Refractory Solid Tumors	Drug: Ixabepilone	Phase II

Further study details as provided by National
Institutes of Health Clinical Center (CC):

Expected Total Enrollment:  120

Background:
Ixabepilone (BMS-247550) is a semi-synthetic analog of the natural
product epothilone B. The epothilones are a novel class of non-taxane
microtubule-stabilizing agents obtained from the fermentation of the
cellulose degrading myxobacteria, Sorangium cellulosum. Ixabepilone is
active against preclinical cancer models that are naturally insensitive
to paclitaxel or have developed resistance to paclitaxel, both in-vitro
and in-vivo. The National Cancer Institute (NCI) Pediatric Oncology
Branch is conducting a phase I trial of Ixabepilone on a daily x 5
consecutive day schedule. The drug has been well tolerated in children
at doses of up to 8 mg/m(2)/d.

Objectives: This Phase
II trial is designed to establish the objective response rate (CR+PR)
using RECIST criteria of Ixabepilone in solid tumors occurring in
pediatric and young adult patients. Time to disease progression is a
secondary trial endpoint. In addition, for patients with measurable
chest disease, comparison of automated volumetric tumor measurement
with standard RECIST and WHO methods is a secondary endpoint on this
trial.

Eligibility: Patients
will be accrued in one of six disease strata: osteosarcoma, Ewing's
sarcoma/Peripheral neuroectodermal tumor (PNETs), rhabdomyosarcoma,
synovial sarcoma and malignant peripheral nerve sheath tumor (MPNSTs),
neuroblastoma, or Wilms tumor. Patients are eligible if they have
measurable disease and have not previously received taxanes. Patients
must be greater than or equal to 12 months old at trial entry. Patients
with sarcoma must have been less than or equal to 35 years old at
original diagnosis; patients with Wilms tumor or neuroblastoma must
have been less than or equal to 21 years old at original diagnosis.

Design: Ixabepilone
will be administered as a one-hour infusion on Days 1 to 5 every 21
days at a dose of 8 mg/m(2)/dose. The trial will use a two-stage design
targeting a response rate of 30%. Up to 20 patients will be accrued to
each tumor stratum.

Genders Eligible for
Study:  Both

Criteria

INCLUSION CRITERIA:

Important note: The
eligibility criteria listed below are interpreted literally and cannot
be waived (per COG policy posted 5/11/01). All clinical and laboratory
data required for determining eligibility of a patient enrolled on this
trial must be available in the patient's medical/research record which
will serve as the source document for verification at the time of
audit.

Age

-Patients must be
greater than or equal to 12 months old at trial entry.

-Patients with
neuroblastoma or Wilms tumor must have been less than 22 years of age
when originally diagnosed with the malignancy to be treated on this
protocol.

-All other patients
must have been less than 36 years of age when originally diagnosed with
the malignancy to be treated on this protocol.

Histologic Diagnosis

The target tumors are:

-Embryonal or alveolar
rhabdomyosarcoma

-Osteosarcoma

-Ewing's
sarcoma/Peripheral neuroectodermal tumor (PNET)

-Synovial sarcoma or
malignant peripheral nerve sheath tumor (MPNST)

-Wilms tumor

-Neuroblastoma

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

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

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.

For patients with
neuroblastoma:

Patients with either
clinically or radiographically measurable disease or evaluable disease
by 123I-MIBG or bone scan are eligible.

-For evaluable tumor,
(123)I-MIBG or bone scan must be positive at a minimum of one site. If
the lesion was previously radiated, a biopsy must be done at least 6
weeks after radiation is complete and demonstrate viable neuroblastoma.

Performance Level

Patients must have an
ECOG performance status of 0, 1 or 2, or Karnofsky greater than or
equal to 50% (patients greater than 16 years of age) or Lansky greater
than or equal to 50% (patients less than or equal to 16 years).

Life Expectancy

Patients must have a
life expectancy of greater than or equal to 8 weeks.

Prior Therapy

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

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

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

-XRT: greater than or
equal to 2 wks for local palliative XRT (small port); greater than or
equal to 6 months must have elapsed if prior craniospinal XRT or if
greater than or equal to 50% radiation of pelvis; greater than or equal
to 6 wks must have elapsed if other substantial BM radiation.

-Stem Cell Transplant
(SCT): No evidence of active graft vs. host disease. For allogeneic
SCT, greater than or equal to 4 months must have elapsed; for
autologous SCT greater than or equal to 2 months must have elapsed.

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

Concomitant
Medications Restrictions

No other cancer
chemotherapy or immunomodulating agents (including steroids) will be
used. However, steroids may be used for the treatment and prevention of
hypersensitivity reactions, if necessary.

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

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

-Antibiotics:
clarithromycin, erythromycin, troleandomycin

-Antifungals:
itraconazole, ketoconazole, fluconazole (doses greater than 3
mg/kg/day), voriconazole

-Antidepressants:
nefazodone, fluovoxamine

-Calcium channel
blockers: verapamil, diltiazem

-Antiemetics: Do not
use aprepitant (Emend® (Registered Trademark)) as it is CYP3A4
substrate, moderate inhibitor and inducer.

-Miscellaneous:
amiodarone,

-In addition,
grapefruit juice should be avoided, as it inhibits CYP3A4.

-Patients must also
avoid St. John's Wort, an inducer of CYP3A4.

-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)

Organ Function
Requirements

All patients must have:

Adequate Bone Marrow
Function Defined As

-Peripheral absolute
neutrophil count (ANC) greater than or equal to 1500/uL (off growth
factors)

-Platelet count
greater than or equal to 75,000/uL (transfusion independent)

-Hemoglobin greater
than or equal to 10.0 gm/dL (may receive RBC transfusions)

Adequate Renal
Function Defined As

Creatinine clearance
or radioisotope GFR greater than or equal to 60mL/min/1.73m(2)

OR

A serum/plasma
creatinine calculation of GFR 60mL/min/1.73m(2) using the Schwartz
formula

(Schwartz et al. J.
Peds, 106:522, 1985)

Estimated Creatinine
Clearance (in mL/min/1.73 m(2))

(k)(L)/Pcr

Where L &eq;
child's length in cm

Pcr &eq; plasma
(or serum) creatinine (in mg/dL)

K Values &eq;

0.33 low birth weight
infant

0.45 term infant

0.55 child

0.55 adolescent female

0.70 adolescent male

**The conversion
formula for serum/plasma creatinine when reported in

uMol/L units:

(k ” ht)/(sCr in
uMol/L ” 88.4)

Adequate Liver
Function Defined As

-Total bilirubin less
than or equal to 1.5 x upper limit of normal (ULN) for age, and

-SGPT (ALT) less than
or equal to 2.5 x upper limit of normal (ULN) for age.

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 less
than or equal to Grade 2.

-Existing sensory or
motor neuropathy must be grade less than or equal to1.

EXCLUSION CRITERIA:

-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.

-Pregnant or
breast-feeding females, because Ixabepilone may be harmful to the
developing fetus or nursing child. Patients of child-bearing potential
must use appropriate birth control measures.

-Patients with known
severe prior hypersensitivity reaction to agents containing Cremophor
EL.

-Patients with active
brain metastases.

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.

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.

Please refer to this study by ClinicalTrials.gov
identifier  NCT00318526

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda, 
Maryland,  20892,  United States; Recruiting

Study ID Numbers:  060146; 06-C-0146
Last Updated:  June 3, 2006
Record first received:  April 25, 2006
ClinicalTrials.gov Identifier:  NCT00318526
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this
record on 2006-07-03