Clinical trial NCT00571675: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hormone Refractory Prostate Cancer
Keywords: Prostate Cancer
Hormone Refractory Prostate Cancer
HRPC
Docetaxel
Taxotere
Prednisone
Metastatic (Stage IV) Disease
Chemotherapy-naïve metastatic Hormone Refractory Prostate Cancer (HRPC)
Lead sponsor: Ascenta Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-12-12
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Further Study Details provided by Ascenta.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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
3. Serum testosterone level ≤ 50 ng/dL post orchiectomy or while maintained on continuous or intermittent medical androgen suppression with a LHRH agonist or antagonist.
4. 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
5. 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.
6. ECOG performance status ≤ 2
7. Able to swallow and retain oral medication

Exclusion Criteria:

1. 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.
2. Patients must not be receiving concurrent anti-androgen hormonal therapy for HRPC (LHRH directed therapies are acceptable to maintain castrate levels of testosterone).
3. 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.
4. Known history of or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
5. Active secondary malignancy or history of other malignancy within the last 5 years
6. Prior history of radiation therapy to ≥ 30% of the bone marrow
7. Peripheral neuropathy of ≥ Grade 2
8. 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.
9. Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
10. Known active symptomatic fungal, bacterial and/or viral infection including active HIV. Note: screening for viruses is not required.
11. Psychiatric illness/social situations that would limit compliance with the study requirements.

Primary outcomes:
measure: To evaluate and compare the two treatment arms with respect to overall survival (OS)
timeFrame: 33 months
Secondary outcomes:
measure: 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.
timeFrame: 33 months
measure: To determine the toxicities associated with oral AT-101 administered in combination with docetaxel and prednisone.
timeFrame: 28 months
measure: To evaluate PSA and objective tumor response rate.
timeFrame: 28 months
Other outcomes:
Locations:
city: Colorado Springs
country: United States
state: Colorado
city: New Port Richey
country: United States
state: Florida
city: Ocoee
country: United States
state: Florida
city: Fishers
country: United States
state: Indiana
city: Burnsville
country: United States
state: Minnesota
city: Las Vegas
country: United States
state: Nevada
city: Albuquerque
country: United States
state: New Mexico
city: Las Cruces
country: United States
state: New Mexico
city: Raleigh
country: United States
state: North Carolina
city: Kettering
country: United States
state: Ohio
city: Eugene
country: United States
state: Oregon
city: Spartanburg
country: United States
state: South Carolina
city: Amarillo
country: United States
state: Texas
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Denton
country: United States
state: Texas
city: Midland
country: United States
state: Texas
city: Paris
country: United States
state: Texas
city: Webster
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Kennewick
country: United States
state: Washington
city: Vancouver
country: United States
state: Washington
city: Barnaul
country: Russian Federation
city: Engels
country: Russian Federation
city: Kazan
country: Russian Federation
city: Kursk
country: Russian Federation
city: Kuzmolovsky
country: Russian Federation
city: Moscow
country: Russian Federation
city: Sochi
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Yekaterinburg
country: Russian Federation
Study officials:
affiliation: Ascenta Therapeutics
name: Lance Leopold, MD
role: STUDY_DIRECTOR
References:
citation: O'Neill AJ, Prencipe M, Dowling C, Fan Y, Mulrane L, Gallagher WM, O'Connor D, O'Connor R, Devery A, Corcoran C, Rani S, O'Driscoll L, Fitzpatrick JM, Watson RW. Characterisation and manipulation of docetaxel resistant prostate cancer cell lines. Mol Cancer. 2011 Oct 7;10:126. doi: 10.1186/1476-4598-10-126.