ABT-751 in Treating Young Patients With Refractory Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as ABT-751, work in different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects of ABT-751 in treating young patients with refractory solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose and dose-limiting toxic effects of ABT-751 administered daily for 7 days every 21 days or daily for 21 days every 28 days in children with refractory solid tumors. Determine the toxicity spectrum of these regimens in these patients. Determine the pharmacokinetics of these regimens in these patients. Evaluate the pharmacodynamics of this drug by measuring the fraction of tubulin that is polymerized in the peripheral blood mononuclear cells of these patients before and after receiving this drug. Secondary Quantify responses in patients treated with these regimens. Assess the effect of this drug on tumor vascularity and tumor blood flow using dynamic enhanced MRI in these patients. OUTLINE: This is an open-label, multicenter, dose-escalation study of 2 different schedules of ABT-751. Patients are assigned to 1 of 2 dosing schedules. Schedule 1 (closed to accrual as of 5/25/2009): Patients receive oral ABT-751 once daily on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Schedule 2 (closed to accrual as of 5/25/2009): Patients receive oral ABT-751 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. On each schedule, cohorts of 3-6 patients receive escalating doses of ABT-751 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 9 patients (a minimum of 3 patients age 11 and under and 3 patients age 12 to 18) are treated at the MTD. PROJECTED ACCRUAL: A maximum of 90 patients will be accrued for this study within 8 months.

Official Title
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Phase I Trial and Pharmacokinetic Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, on a 7 Day and 21 Day Dosing Schedule in Pediatric Patients With Refractory Solid Tumors

Conditions
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Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor, Kidney Cancer, Liver Cancer, Neuroblastoma, Ovarian Cancer, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: ABT-751


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed solid tumor*, including, but not limited to, the following: Rhabdomyosarcoma Other soft tissue sarcomas Ewing's sarcoma family of tumors Osteosarcoma Neuroblastoma Wilms' tumor Hepatic tumors Germ cell tumors Primary brain tumors Brain stem or optic gliomas (histological confirmation may be waived if a biopsy has not been performed) NOTE: *Closed to accrual for all diagnoses except neuroblastoma as of 4/16/05 Relapsed after or failed to respond to frontline standard therapy and no other standard treatment options (e.g., surgery, radiotherapy, chemotherapy, or any combination of these modalities) exist Measurable or evaluable disease* NOTE: *Not required for patients with neuroblastoma No CNS tumor with motor or sensory deficits that would obscure the study assessment of sensory neuropathy PATIENT CHARACTERISTICS: Age: 18 and under Performance status: Lansky 60-100% (age 10 and under) Karnofsky 60-100% (age 11 to 18) Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) ALT and AST no greater than 2.5 times ULN (5 times ULN for patients treated after the maximum tolerated dose is determined) No clinically significant hepatic dysfunction Renal: Creatinine normal for age OR Creatinine clearance at least 60 mL/min No clinically significant renal dysfunction Cardiovascular: LVEF normal by echocardiogram Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No allergy to sulfa-containing medications No clinically significant unrelated systemic illness (e.g., other organ dysfunction) that would preclude study participation No serious infection No preexisting grade 2 or greater sensory or motor neuropathy HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 months since prior bone marrow transplantation At least 72 hours since prior interleukin-11 At least 72 hours since prior colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) except epoetin alfa No concurrent growth factors (e.g., GM-CSF) except epoetin alfa Concurrent G-CSF allowed if neutropenia lasts longer than 5 days OR if the patient experiences confirmed septicemia associated with neutropenia No concurrent immunotherapy No concurrent interleukin-11 Chemotherapy: See Disease Characteristics At least 30 days since prior chemotherapy (42 days for nitrosoureas) No other concurrent anticancer chemotherapy Endocrine therapy: Patients with brain tumors: Must be on a stable or tapering dose of corticosteroids for 7 days before baseline scan performed for the purpose of assessing response to study therapy Concurrent corticosteroids allowed for control of symptoms of tumor-associated edema Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy At least 4 months since prior extensive radiotherapy (craniospinal radiotherapy, total body irradiation, or radiotherapy to more than 50% of the pelvis) No concurrent radiotherapy Surgery: See Disease Characteristics Other: Recovered from prior therapy At least 30 days since prior investigational anticancer therapy No other concurrent investigational agents

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ABT-751|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood teratoma, metastatic osteosarcoma, childhood infratentorial ependymoma, recurrent childhood rhabdomyosarcoma, childhood supratentorial ependymoma, childhood craniopharyngioma, disseminated neuroblastoma, recurrent neuroblastoma, recurrent childhood liver cancer, stage IV childhood liver cancer, recurrent Wilms tumor and other childhood kidney tumors, stage IV Wilms tumor, childhood central nervous system germ cell tumor, recurrent osteosarcoma, unspecified childhood solid tumor, protocol specific, childhood germ cell tumor, metastatic childhood soft tissue sarcoma, recurrent childhood soft tissue sarcoma, childhood high-grade cerebral astrocytoma, childhood oligodendroglioma, childhood choroid plexus tumor, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood medulloblastoma, recurrent childhood visual pathway and hypothalamic glioma, previously treated childhood rhabdomyosarcoma, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent childhood ependymoma, childhood malignant testicular germ cell tumor, childhood malignant ovarian germ cell tumor, childhood extragonadal germ cell tumor, recurrent childhood malignant germ cell tumor