Clinical trial NCT00471718: ABT-751 in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy
Official title: A Phase1/2 Trial of ABT-751 in Patients With Advanced, Androgen-Independent Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-10
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: OBJECTIVES:

Primary

* 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.

Secondary

* 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 dose.

* 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.

Eligibility criteria: 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:

  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 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:

* 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: up to four weeks
measure: Number of Patients Who Demonstrated Treatment Effectiveness Based on Prostate Specific Antigen (PSA) Response in Non-measurable Disease
timeFrame: after four weeks
Secondary outcomes:
measure: Number of Patients With Objective Response (CR & PR) by RECIST
timeFrame: after four weeks
measure: Median Time to Tumor Progression
timeFrame: date on study to date of progression
measure: Overall Survival
timeFrame: date on study to date of death from any cause
measure: Safety Profile Based on Number of Patients With Worst Grade Toxicities
timeFrame: at 30 days after final treatment dose
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Jeff Sosman, MD
role: PRINCIPAL_INVESTIGATOR
References: