A Study Comparing AT-101 in Combination With Docetaxel and Prednisone Versus Docetaxel and Prednisone in Men With Chemotherapy-Naïve Metastatic Hormone Refractory Prostate Cancer (HRPC)

Sponsor

Ascenta Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT00571675

Collaborator

(none)

220

Enrollment

Locations

Arms

Duration (Months)

6.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, multinational Phase 2 study to evaluate and compare oral AT-101 in combination with docetaxel and prednisone versus docetaxel and prednisone plus placebo in the treatment of chemotherapy-naïve metastatic hormone-refractory prostate cancer, who have received hormonal therapy but not chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Hormone Refractory Prostate Cancer	Drug: AT-101, prednisone and docetaxel Drug: placebo, prednisone and docetaxel	Phase 2

Detailed Description

Further Study Details provided by Ascenta.

Study Design

Study Type:

Interventional

Actual Enrollment :

220 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Study Comparing AT-101 in Combination With Docetaxel and Prednisone Versus Docetaxel and Prednisone in Men With Chemotherapy-Naïve Metastatic Hormone Refractory Prostate Cancer (HRPC)

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 AT-101, prednisone and docetaxel	Drug: AT-101, prednisone and docetaxel docetaxel (75mg/m2 intravenously over 1 hour on day 1, every 21 days [one cycle]), oral prednisone (5mg BID on days 1-21), and oral AT-101 on cycle days 1-3
Placebo Comparator: 2 Placebo, prednisone and docetaxel	Drug: placebo, prednisone and docetaxel docetaxel (75mg/m2 intravenously over 1 hour every 21 days [one cycle]), oral prednisone (5mg BID on days 1-21), and oral placebo on cycle days 1-3

Arm

Intervention/Treatment

Experimental: 1

AT-101, prednisone and docetaxel

Drug: AT-101, prednisone and docetaxel

docetaxel (75mg/m2 intravenously over 1 hour on day 1, every 21 days [one cycle]), oral prednisone (5mg BID on days 1-21), and oral AT-101 on cycle days 1-3

Placebo Comparator: 2

Placebo, prednisone and docetaxel

Drug: placebo, prednisone and docetaxel

docetaxel (75mg/m2 intravenously over 1 hour every 21 days [one cycle]), oral prednisone (5mg BID on days 1-21), and oral placebo on cycle days 1-3

Outcome Measures

Primary Outcome Measures

To evaluate and compare the two treatment arms with respect to overall survival (OS) [33 months]

Secondary Outcome Measures

To evaluate and compare progression-free survival (PFS) in men with chemotherapy-naïve metastatic HRPC treated with AT-101 in combination with docetaxel and prednisone versus docetaxel and prednisone plus placebo. [33 months]
To determine the toxicities associated with oral AT-101 administered in combination with docetaxel and prednisone. [28 months]
To evaluate PSA and objective tumor response rate. [28 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males age ≥ 18 years with histologically confirmed adenocarcinoma of the prostate, which is now metastatic (e.g. any T, any N, M1a-c) based on bone scan, CT scan, or MRI scan.
Progression of disease despite androgen deprivation (androgen ablation or surgical castration) and anti-androgen withdrawal as documented by one or more of the following.

Progression of measurable disease per RECIST
Bone scan progression, defined as the appearance of ≥ 2 new lesions on bone scan, attributable to prostate cancer
Rising PSA, as defined by increasing levels on at least two consecutive assessments, following a prior assessment taken as a reference value, where all of the following are met:
The assessments are at least one week apart, with the first assessment at least one week later than the reference value
Progressive increase in the two assessments after the reference value, without an intervening decrease between assessments.
The last value prior to study entry is ≥ 2 ng/mL

Serum testosterone level ≤ 50 ng/dL post orchiectomy or while maintained on continuous or intermittent medical androgen suppression with a LHRH agonist or antagonist.
At least 2 weeks since ketoconazole or systemic steroids (any dose); 2 weeks since prior flutamide, megestrol, or aminoglutethimide; and at least 2 weeks since prior bicalutamide or nilutamide
Radiation therapy and/or therapy with samarium must have been completed 4 weeks prior to first dose of therapy. Strontium therapy must have been completed at least 12 weeks prior to the first dose of therapy. The patient must have recovered from all treatment-related toxicities.
ECOG performance status ≤ 2
Able to swallow and retain oral medication

Exclusion Criteria:

Received prior chemotherapy (including estramustine phosphate [Estracyt]) for HRPC. Adjuvant chemotherapy (including docetaxel) is allowed provided that progression of disease occurred ≥ 6 months after the completion of adjuvant therapy.
Patients must not be receiving concurrent anti-androgen hormonal therapy for HRPC (LHRH directed therapies are acceptable to maintain castrate levels of testosterone).
Treatment with monoclonal antibody (e.g., VEGF targeting antibody) or prostate cancer vaccine within 45 days prior to the first dose of study treatment. Acute toxicities from prior therapy must have resolved to Grade ≤ 1.
Known history of or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
Active secondary malignancy or history of other malignancy within the last 5 years
Prior history of radiation therapy to ≥ 30% of the bone marrow
Peripheral neuropathy of ≥ Grade 2
Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction are also excluded.
Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
Known active symptomatic fungal, bacterial and/or viral infection including active HIV. Note: screening for viruses is not required.
Psychiatric illness/social situations that would limit compliance with the study requirements.

Contacts and Locations

Locations

	City	State	Country
1	Colorado Springs	Colorado	United States
2	New Port Richey	Florida	United States
3	Ocoee	Florida	United States
4	Fishers	Indiana	United States
5	Burnsville	Minnesota	United States
6	Las Vegas	Nevada	United States
7	Albuquerque	New Mexico	United States
8	Las Cruces	New Mexico	United States
9	Raleigh	North Carolina	United States
10	Kettering	Ohio	United States
11	Eugene	Oregon	United States
12	Spartanburg	South Carolina	United States
13	Amarillo	Texas	United States
14	Arlington	Texas	United States
15	Austin	Texas	United States
16	Dallas	Texas	United States
17	Denton	Texas	United States
18	Midland	Texas	United States
19	Paris	Texas	United States
20	Webster	Texas	United States
21	Fairfax	Virginia	United States
22	Norfolk	Virginia	United States
23	Kennewick	Washington	United States
24	Vancouver	Washington	United States
25	Barnaul		Russian Federation
26	Engels		Russian Federation
27	Kazan		Russian Federation
28	Kursk		Russian Federation
29	Kuzmolovsky		Russian Federation
30	Moscow		Russian Federation
31	Sochi		Russian Federation
32	St. Petersburg		Russian Federation
33	Stavropol		Russian Federation
34	Voronezh		Russian Federation
35	Yekaterinburg		Russian Federation