Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy
Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy
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.
OBJECTIVES:

 Primary

 -  Compare the potential benefit of bisphosphonate therapy comprising zoledronate plus
 vitamin D and calcium supplement vs standard therapy with vitamin D and calcium
 supplement in the prevention of osteoporosis and associated bone fractures in patients
 with locally advanced nonmetastatic adenocarcinoma of the prostate undergoing
 radiotherapy and luteinizing hormone-releasing hormone (LHRH) agonist therapy.

 Secondary

 -  Evaluate the potential benefit of these regimens on quality of life in these patients.

 -  Evaluate the potential benefit in bone mineral density over a period of 3 years for
 patients treated with these regimens.

 OUTLINE: This is randomized multicenter study. Patients are stratified according to T score
 of the hip by dual x-ray absorptiometry (DXA) scan (< -1.0 but > -2.5 vs ≥ - 1.0) and planned
 duration of luteinizing hormone-releasing hormone (LHRH) agonist therapy (1-2½ years vs > 2½
 years). Patients are randomized to 1 of 2 treatment arms.

 Quality of life is assessed at baseline and every 6 months during treatment.
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