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Phase I Study of 7-Day or 21-Day ABT-751 in Children With Refractory Solid Tumors
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Published Results Trial Contact Information Registry Information
Alternate Title
ABT-751 in Treating Young Patients With Refractory Solid Tumors
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
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Phase I | Treatment | Closed | 18 and under | NCI-02-C-0141L ABBOTT-M01-357, NCT00036959 |
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.
Entry Criteria Disease Characteristics:
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
Patient Characteristics:
Age: Performance status: - Lansky 60-100% (age 10 and under)
- Karnofsky 60-100% (age 11 to 18)
Life expectancy: Hematopoietic: - Absolute neutrophil count at least 1,500/mm3
- Platelet count at least 100,000/mm3
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
Expected Enrollment 90A maximum of 90 patients will be accrued for this study within 8 months. 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: 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: 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. Published ResultsFox E, Maris JM, Widemann BC, et al.: A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors. Clin Cancer Res 14 (4): 1111-5, 2008.[PUBMED Abstract] Fox E, Maris JM, Widemann BC, et al.: A phase 1 study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 7 days every 21 days in pediatric patients with solid tumors. Clin Cancer Res 12 (16): 4882-7, 2006.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations NCI - Center for Cancer Research | | | Frank Balis, MD, Principal investigator | | | |
Registry Information | | 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 | | Trial Start Date | | 2002-03-21 | | Registered in ClinicalTrials.gov | | NCT00036959 | | Date Submitted to PDQ | | 2002-03-21 | | Information Last Verified | | 2007-06-04 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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