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A Phase1/2 Trial of ABT-751 in Patients With Advanced, Androgen-Independent Prostate Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

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.

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

- 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

- The patient must have an ECOG Performance Status of 0-1

- The patient must have adequate hematologic, renal and hepatic function as follows:

1. Hematologic: ANC > 1200/mm3; hemoglobin > 9.0 g/dl; platelets > 100,000/mm3

2. Renal: serum creatinine < 2.0 mg/dL

3. Hepatic: bilirubin < 2.5 mg/dL; AST and ALT < 2.5X upper limit of normal (ULN);
< 5X ULN for patients with hepatic metastases

- 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

- 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:

- No active angina pectoris, uncontrolled hypertension, or known heart disease of New
York Heart Association Class III-IV. Patients must not have a history of myocardial
infarction, congestive cardiac failure (New York Heart Association Class 3), or
coronary angioplasty/stenting < 6 months prior to entry.

- No carcinomatous meningitis or brain metastases.

- Any investigational therapy within 4 weeks.

- No serious concurrent medical illness or active infection, which, in the opinion of
the investigator, would jeopardize the ability of the patient to receive the
chemotherapy outlined in this protocol with reasonable safety.

- Documented history of allergy to sulfa medications.

- Current colchicines treatment

- Greater than Grade 1 CTC neurology category findings (Appendix A).

- Prior treatment with more than 1 prior chemotherapy regimen.

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

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.

Outcome Time Frame:

up to four weeks

Safety Issue:


Principal Investigator

Jeff Sosman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2004

Completion Date:

August 2009

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • stage IV prostate cancer
  • recurrent prostate cancer
  • Prostatic Neoplasms



Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838