A Phase1/2 Trial of ABT-751 in Patients With Advanced, Androgen-Independent Prostate Cancer
A Phase1/2 Trial of ABT-751 in Patients With Advanced, Androgen-Independent Prostate Cancer
RATIONALE: Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I/II trial is studying the side effects and best dose of ABT-751 and to see how well it works in treating patients with metastatic prostate cancer that did not respond to hormone therapy.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
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 dose.
PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Inclusion Criteria:
Patients at least 18 years of age.
Patients must have histologically proven adenocarcinoma of the prostate gland.
Patients must have metastatic disease (e.g. bone metastases, pelvic mass, nodal, liver or lung metastases), with evidence of radiographic progression (including bone scans observed during last treatment) or serologically -Patients with bone-only metastases (i.e. lacking soft tissue or visceral disease) must have a PSA level > 10 ng/mls. Patients with soft tissue metastases and/or visceral disease must have either measurable disease OR a PSA level > 10 ng/ml.
Patients must have had prior treatment with bilateral orchiectomy or other primary hormonal therapy (e.g. LHRH therapy, estrogens, etc.) with evidence of treatment failure and simultaneous documentation of a castrate testosterone level (< 50 ng/dL) NOTE: Patients who have not undergone bilateral orchiectomy must continue LHRH agonist therapy for the duration of this protocol unless this medically contraindicated.
For patients previously treated with flutamide, nilutamide, or bicalutamide: patients must have discontinued flutamide or nilutamide > 4 weeks prior to randomization (> 6 weeks for bicalutamide) with no evidence of an anti-androgen withdrawal response (i.e. no decline in serum PSA and/or no improvement in baseline scans).
Patients must have received prior therapy with docetaxel alone or in combination with either prednisone or estramustine. This therapy may have been given in a neoadjuvant, adjuvant or metastatic setting
Patients must not have received radiotherapy < 3 weeks prior to randomization. If patients have received prior radiotherapy to an evaluable lesion(s), there must be evidence of radiographic progression prior to entry.
Patients must not have received prior Strontium 89, Samarium 153, or other therapeutic radioisotopes.
Patients must have recovered from all systemic toxicities due to prior treatment for prostate cancer (does not include incontinence, impotence, etc. secondary to primary therapy)
The patient must have an ECOG Performance Status of 0-1
The patient must have adequate hematologic, renal and hepatic function as follows:
Sexually-active patients must use a contraceptive method deemed acceptable by the investigator while in the study and for up to 3 months following completion of therapy.
The patient or the patient's legally acceptable representative has voluntarily signed and dated an informed consent approved by and Institutional Review Board prior to any study any study specific procedures.
Patients may be receiving bisphosphonate therapy prior to randomization and continue while receiving protocol therapy, but must not begin treatment with bispohosphonates while receiving protocol therapy. Patients on bisphosphonates must have completed at least 4 weeks of bisphosphonate therapy prior to entry onto study.
Patients with a history of a prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for the specific malignancy.
Exclusion Criteria: