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)

This study has been completed.
Sponsor:
Information provided by:
Ascenta Therapeutics
ClinicalTrials.gov Identifier:
NCT00571675
First received: December 11, 2007
Last updated: November 8, 2010
Last verified: November 2010
  Purpose

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 Intervention Phase
Hormone Refractory Prostate Cancer
Drug: AT-101, prednisone and docetaxel
Drug: placebo, prednisone and docetaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by Ascenta Therapeutics:

Primary Outcome Measures:
  • To evaluate and compare the two treatment arms with respect to overall survival (OS) [ Time Frame: 33 months ] [ Designated as safety issue: No ]

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. [ Time Frame: 33 months ] [ Designated as safety issue: Yes ]
  • To determine the toxicities associated with oral AT-101 administered in combination with docetaxel and prednisone. [ Time Frame: 28 months ] [ Designated as safety issue: No ]
  • To evaluate PSA and objective tumor response rate. [ Time Frame: 28 months ] [ Designated as safety issue: No ]

Enrollment: 220
Study Start Date: October 2007
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

Further Study Details provided by Ascenta.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00571675

  Show 35 Study Locations
Sponsors and Collaborators
Ascenta Therapeutics
Investigators
Study Director: Lance Leopold, MD Ascenta Therapeutics
  More Information

No publications provided by Ascenta Therapeutics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Melissa Brookes, Sr. Project Manager, Clinical Development, Ascenta Therapeutics
ClinicalTrials.gov Identifier: NCT00571675     History of Changes
Other Study ID Numbers: AT-101-CS-205
Study First Received: December 11, 2007
Last Updated: November 8, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Ascenta Therapeutics:
Prostate Cancer
Hormone Refractory Prostate Cancer
HRPC
Docetaxel
Taxotere
Prednisone
Metastatic (Stage IV) Disease
Chemotherapy-naïve metastatic Hormone Refractory Prostate Cancer (HRPC)

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Gossypol
Gossypol acetic acid
Docetaxel
Prednisone
Hormones
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Contraceptive Agents, Female
Spermatocidal Agents
Antispermatogenic Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Glucocorticoids
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 16, 2014