ABT-751 in Treating Young Patients With Refractory Solid Tumors

Sponsor

National Institutes of Health Clinical Center (CC) (NIH)

Overall Status

Completed

CT.gov ID

NCT00036959

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

95.1

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: ABT-751	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2002

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Feb 1, 2010

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
2	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892-1182
3	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-4318