Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy
Condition: Osteoporosis; Prostate Cancer
MeSH terms: Prostatic Neoplasms; Osteoporosis
Intervention: Calcium; Zoledronic acid; radiation therapy; LHRH; Vitamin D
Intervention description: A single dose of 500 mg of elemental calcium orally each day for 3 years.; Patients receive IV over 15 minutes once every 6 months for 3 years. The goal dose of zoledronic acid is 4 mg, but the selection of dose is determined based on calculated creatinine clearance at baseline.; Patients must receive external beam irradiation, brachytherapy (HDR or LDR), or a combination of external beam irradiation and brachytherapy at the discretion of the treating physician. Dose/duration also will be at the discretion of the treating physician; however, dose will not exceed 45 Gy to 100% of the proximal femur, and no proximal femur will receive ≥ 60 Gy.; LHRH therapy must take place for a minimum of one year. Choice of LHRH agonist, dose, and duration are at the discretion of the treating physician.; 400 IU (10μg), orally each day for 3 years.
Intervention MeSH terms: Vitamin D; Zoledronic Acid; Calcium
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 109.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: osteoporosis; adenocarcinoma of the prostate; stage IIB prostate cancer; stage IIA prostate cancer; stage III prostate cancer; stage IV prostate cancer

Summary:

      RATIONALE: Zoledronate may prevent bone loss in patients with prostate cancer undergoing
      radiation therapy and hormone therapy. It is not yet known whether zoledronate is more
      effective than calcium and vitamin D alone in preventing osteoporosis and bone fractures in
      patients with prostate cancer.

      PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works
      compared to calcium and vitamin D alone in preventing osteoporosis and bone fractures in
      patients with locally advanced nonmetastatic prostate cancer undergoing radiation therapy and
      hormone therapy.
    

Eligibility criteria:

        Eligibility criteria:

          -  Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of
             the prostate within 12 months of registration;

          -  Any one of the following clinical stages:

               -  T3 disease, any N stage, M0 with any Gleason score and any prostate-specific
                  antigen (PSA); < T3 stage, any N stage, M0 with Gleason's score ≥ 8 and any PSA;
                  < T3 stage, any N stage, M0 with Gleason's score 7 and PSA ≥ 15 nanograms/ml; <
                  T3 stage, any N stage, M0 with Gleason score < 7 and PSA ≥ 20 nanograms/ml.

          -  A negative bone scan for metastatic disease;

          -  It is mandatory that the treating physician determine the planned duration of LHRH
             therapy prior to the site registering the patient (minimum 1 year of therapy); If
             patient is receiving pre-treatment LHRH therapy, it must have begun ≤ 6 months prior
             to registration. If pelvic radiation therapy (RT) has started, it must have begun ≤ 8
             weeks prior to registration;

          -  Appropriate stage for protocol entry, including no distant metastases, based upon the
             following minimum diagnostic workup to be done within 16 weeks prior to registration:

          -  History/physical examination;

          -  Dental evaluation, including history of dental surgery (e.g., extraction or implant);

          -  Bone scan;

          -  T and L spine films;

          -  DXA scan: To be eligible the patient must have a scan on Lunar, Hologic, or Norland
             equipment only and the T scores in both the L spine and total hip must be > negative
             2.5;

          -  Zubrod Performance Status 0-1 within 16 weeks prior to registration; (8/16/07)

          -  Age ≥ 18;

          -  Serum creatinine within 4 weeks prior to registration (8/16/07)

          -  Corrected serum calcium ≥ 8.4 and ≤ 10.6 mg/dl within 8 weeks prior to registration;
             note: for patients with an albumin of 4.0, corrected calcium=measured calcium. The
             formula for corrected calcium if serum albumin value is above or below 4.0 is as
             follows: Corrected calcium (mg/dl) = (4 - [patient's albumin (g/dl)] x 0.8) +
             patient's measured calcium (mg/dl)

          -  Patients who are sexually active must be willing/able to use medically acceptable
             forms of contraception, as the treatment involved in this study may be significantly
             teratogenic.

          -  Patient agrees to refrain from using all products listed in Section 9.2,
             "Non-permitted Supportive Therapy";

          -  Post-prostatectomy patients are eligible.

          -  Patient must sign study specific informed consent prior to study entry.

        Ineligibility criteria:

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years; e.g., carcinoma in situ of the breast or oral cavity are
             permissible;

          -  Patients with baseline T scores of ≤ -2.5 are excluded.

          -  Patients with baseline calculated creatinine clearance < 30 mL/min (estimated by
             Cockcroft-Gault formula below) are excluded. creatinine clearance male = [(140 - age)
             x (wt in kg)] / [(serum creatinine) x (72)]

          -  Prior bisphosphonate therapy;

          -  Prior pelvic radiation (other than for current prostate cancer) or prior systemic
             radiotherapeutic agents, such as strontium or samarium;

          -  Patients receiving systemic chemotherapy, steroids, growth hormones, or calcitonin;

          -  Patients with a history of Paget's disease or with uncontrolled thyroid or parathyroid
             dysfunction or with other diseases that influence bone metabolism;

          -  Known hypersensitivity to zoledronic acid or other bisphosphonates;

          -  Active dental problems at study entry, including infection of the teeth or jawbone;
             dental or fixture trauma; or a current or prior diagnosis of osteonecrosis of the jaw,
             exposed bone in the mouth, or slow healing after dental procedures;

          -  Recent or planned