Study of Docetaxel With Doxercalciferol or Placebo for Advanced Prostate Cancer

The purpose of this research study is to find out the toxicities of doxercalciferol given in combination with docetaxel (Taxotere®), as well as to see how well this combination works in the treatment of prostate cancer.

This is a multi-institutional, double-blinded, randomized study comparing docetaxel plus doxercalciferol versus docetaxel plus placebo in patients with metastatic hormone refractory prostate cancer. Docetaxel is given intravenously on days 1, 8 and 15 for every 28 day cycle and doxercalciferol or placebo is taken orally every day of the 28 day cycle. Please refer to the Eligibility Criteria below for key inclusion and exclusion criteria.

• Drug: Docetaxel plus doxercalciferol
  Docetaxel 35mg/m2 IV weekly x3 every 4 weeks plus Doxercalciferol 10mcg orally every day
  Other Names:

  • Taxotere
  • Hectoral
  • 1a,hydroxyvitamin D2
  • 1a-OH-D2
  • 1a-hydroxyerocalciferol
  • Vitamin D analog
  • prodrug of 1a,25-dihydroxyvitamin D2
• Drug: Docetaxel plus placebo
  Docetaxel 35mg/m2 IV weekly x3 every 4 week cycle plus placebo taken orally every day
  Other Name: Taxotere

• Experimental: A
  Docetaxel plus doxercalciferol
  Intervention: Drug: Docetaxel plus doxercalciferol
• Placebo Comparator: B
  Docetaxel plus placebo
  Intervention: Drug: Docetaxel plus placebo

Inclusion Criteria:

• Histologic diagnosis of adenocarcinoma of the prostate.
• evidence of metastatic disease within 4 weeks of registration.

• Must meet ONE of the following:

  1. PSA >or= 10 ng/mL and at least one lesion on bone scan.
  2. Soft tissue metastases and/or visceral disease per CT scan.

• Must show progressing prostate cancer as seen by one of the following:

  1. At least one new lesion on bone scan,
  2. Increase in size or number of measurable disease lesions,
  3. At least 2 rising PSA measurements at least two weeks apart.
• Prior bilateral orchiectomy or on LHRH agonist therapy with a serum testosterone level of < 50.
• Must be off flutamide, nilutamide, or ketoconazole or herbal supplements used to treat prostate cancer at least 4 weeks prior to registration and bicalutamide at least 6 weeks prior to registration.
• No prior cytotoxic chemotherapy.
• WHO performance status of 0-2.
• Peripheral neuropathy must be < or = to grade 1.

Exclusion Criteria:

• A history of a radiographically confirmed kidney stone or pathologically confirmed calcium stone within the last 10 years.
• Patients can continue to take bisphosphonates during the study as long as the bisphosphonate was started at least 4 weeks prior to study entry and the patient continues to demonstrate a rising PSA
• No prior treatment with suramin, strontium or other therapeutic radioisotopes.
• No radiotherapy within the past 4 weeks.
• No known brain metastases.
• No chronic hypercalcemia (serum calcium >1.0 mg/dl above the upper limit of normal range), chronic gastrointestinal disease (malabsorption, surgery affecting absorption, chronic ulcerative colitis) or any condition that the investigator feels would put the patient at undue risk.
• Must not be taking digitalis, thiazide diuretics (or drugs in combination with thiazides) or calcium supplements within one week of treatment initiation.
• No active angina, known heart disease of New York Heart Association Class II-IV or a recent history (< 6 months) of myocardial infarction.
• Must not be taking steroids, anticonvulsants, fluoride, or lithium.
• Must not have urinary protein > 4gm/24 hours
• Must not have urinary calcium > or= 500 mg/24 hours
• No Coexistent second malignancy or history of prior malignancy within previous 5 years (excluding basal or squamous cell carcinoma of the skin that has been treated curatively).

• Sanofi
• Genzyme, a Sanofi Company