Ixabepilone in Treating Young Patients With Refractory Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Adult Synovial Sarcoma

Recurrent Neuroblastoma

Alveolar Childhood Rhabdomyosarcoma

Recurrent Osteosarcoma

Recurrent Childhood Soft Tissue Sarcoma

Embryonal Childhood Rhabdomyosarcoma

Childhood Synovial Sarcoma

Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Recurrent Wilms Tumor and Other Childhood Kidney Tumors

Recurrent Adult Soft Tissue Sarcoma

Adult Rhabdomyosarcoma

Previously Treated Childhood Rhabdomyosarcoma

Recurrent Childhood Rhabdomyosarcoma

Treatments

Drug: ixabepilone

Study type

Interventional

Funder types

NIH

Identifiers

NCT00331643

NCI-06-C-0146

NCI-2012-01826 (Registry Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

COG-ADVL0524

CDR0000472912

ADVL0524 (Other Identifier)

NCI-P6451

Details and patient eligibility

About

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.

Full description

PRIMARY OBJECTIVES:

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.

Enrollment

120 patients

Sex

All

Ages

1 to 35 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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