Zoledronate 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