A Phase1/2 Trial of ABT-751 in Patients With Advanced, Androgen-Independent Prostate Cancer
- Evaluate the safety and efficacy of ABT-751 in patients with androgen-independent,
hormone-refractory metastatic prostate cancer and determine the maximum tolerated dose
(MTD) and optimal phase II dose of this drug in these patients.
- Determine the objective response rate (partial and complete response) in patients with
measurable disease treated with this drug.
- Evaluate the effect of this drug on prostate-specific antigen (PSA) response in
patients with nonmeasurable disease.
- Determine the time to tumor progression in patients treated with this drug.
- Determine survival of patients treated with this drug.
- Determine the toxicity of this drug in these patients.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
- Phase I: Patients receive oral ABT-751 twice daily on days 1-7 and 15-21. Treatment
repeats every 28 days in the absence of disease progression or unacceptable toxicity.
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 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. Up to 50 additional patients may be treated at
the recommended phase II dose (RPTD) which is the dose level at the maximally administered
- Phase II: Patients receive ABT-751 at the MTD determined in phase I. After completion
of study treatment, patients are followed every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
MTD is determined by the 3+3 study design, in which patients are enrolled in cohorts of 3. In any dose cohort, if 1 patient of 3 experience dose-limiting toxicity (DLT), three additional patients will be enrolled at the same dose level. Whenever >=2 of 6 subjects experience a DLT, then the maximum tolerated dose (MTD) has been exceeded. The MTD is generally one dose below that at which DLT occurs in >= 2 of 6 subjects in any given cohort.
up to four weeks
Jeff Sosman, MD
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
VICC URO 0426
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|