Zoledronate, Vitamin D, and Calcium With or Without Strontium 89 or Samarium 153 in Preventing or Delaying Bone Problems in Patients With Bone Metastases From Prostate Cancer, Lung Cancer, or Breast Cancer
Condition: Breast Cancer; Lung Cancer; Metastatic Cancer; Pain; Prostate Cancer
MeSH terms: Breast Neoplasms; Lung Neoplasms; Prostatic Neoplasms; Neoplasm Metastasis
Intervention: Calcium; Vitamin D; zoledronic acid; Sm-153; Sr-89
Intervention description: At least 500 mg of calcium (1 pill) by mouth daily until the study doctor thinks it is in their best interest to stop.; 400 IU of vitamin D (1 pill) by mouth daily until the study doctor thinks it is in their best interest to stop.; 4 mg of Zoledronic acid intravenously once a month until the study doctor thinks it is in their best interest to stop.; Single dose intravenously 1 mCi/kg body weight.; Single dose intravenously 4 mCi.
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: 261.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pain; bone metastases; extensive stage small cell lung cancer; recurrent breast cancer; stage IV breast cancer; recurrent non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent prostate cancer; stage IV prostate cancer

Summary:

      RATIONALE: Zoledronate, vitamin D and calcium may prevent or delay bone pain and other
      symptoms caused by bone metastases. It is not yet known whether giving zoledronate together
      with vitamin D and calcium is more effective with or without strontium 89 or samarium 153 in
      treating patients with bone metastases from prostate cancer, lung cancer, or breast cancer.

      PURPOSE: This randomized phase III trial is studying zoledronate, vitamin D, and calcium to
      see how well they work compared to zoledronate, vitamin D, calcium, and either strontium 89
      or samarium 153 in preventing or delaying bone problems in patients with bone metastases from
      prostate cancer, lung cancer, or breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically or cytologically proven diagnosis of solid tumor malignancy of lung,
             breast, or prostate prior to registration;

          2. Appropriate diagnosis for protocol entry, based upon the following minimum diagnostic
             workup:

             2.1 History/physical examination within 8 weeks prior to registration; 2.2 Bone scan
             within 4 weeks prior to registration; bone metastases must be visible on the scan.
             Other scanning modalities, such as magnetic resonance imaging (MRI), positron emission
             tomography (PET) 2.3 Dental evaluation according to the dental exam checklist (carried
             out by the investigator, the investigator's designee, or by a qualified dental
             professional [dental hygienist or dentist]), including history of dental surgery
             (e.g., extraction or implant) within 8 weeks prior to registration and recorded on the
             dental exam checklist; Note: If the patient has received prior oral bisphosphonate
             therapy and has had a prior dental evaluation within 8 weeks of registration, the
             evaluation should not be repeated.

             2.4 Complete blood count (CBC)/differential within 2 weeks prior to registration, with
             adequate bone marrow function defined as follows:

               -  White blood cell count (WBC) ≥ 2400 cells/mm^3;

               -  Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;

               -  Platelets ≥ 60,000 cells/mm3;

               -  Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to
                  achieve the required hemoglobin is permitted).

             2.5 Serum creatinine < 3 mg/dL (265 μmol/L) within 2 weeks prior to registration; 2.6
             Total bilirubin < 2.5 mg/dL (43 μmol/L) within 2 weeks prior to registration; 2.7
             Pregnancy test (urine dipstick or serum) for women of childbearing potential within 2
             weeks prior to registration;

          3. ≥ 18 years of age;

          4. Zubrod performance status 0-2 for patients with breast or prostate primaries; Zubrod
             performance status 0-1 for patients with lung primaries;

          5. Patients receiving systemic chemotherapy or hormonal therapy are eligible for this
             study. See Sections 6.0 and 7.0 for further details. Note: All patients must complete
             external beam radiation therapy ≥ 14 days prior to registration. If patients have
             undergone CyberKnife treatment, treatment must be completed ≥ 14 days prior to
             registration.

          6. Patients may have received prior oral bisphosphonate therapy, such as Fosamax® or
             similar medications. Duration of bisphosphonate treatment prior to study entry must be
             documented, and all bisphosphonates other than the study drug must be discontinued
             prior to registration.

          7. Women of childbearing potential and male participants must agree to practice an
             adequate means of birth control throughout their participation in the study.

          8. Patient must sign study specific informed consent prior to study entry.

        Exclusion Criteria

          1. Patients with brain metastases and/or spinal cord compression are excluded. Note:
             Patients with no evidence of disease in the brain after treatment for brain metastases
             are eligible.

          2. Patients with painful bone metastases are not permitted until these bone metastases
             are successfully treated (for example by external beam irradiation) prior to
             registration, and the patient has stable pain for at least 2 weeks after that
             treatment (Stable pain is defined for this study as a patient response of 1, 2, or 3
             on Questions 4 and 5 of The Brief Pain Inventory (BPI).

          3. Prior treatment with Strontium-89 or Samarium-153 for bone metastases.

          4. Treatment for more than 6 months with IV bisphosphonates prior to study entry;

          5. Treatment with calcitonin, mithramycin, or gallium nitrate within 2 weeks prior to
             registration

          6. Severe, active co-morbidity, defined as follows:

             6.1 Evidence in the six months prior to study entry of uncontrolled congestive heart
             failure, hypertension refractory to treatment, or symptomatic coronary artery disease;
             6.2 Current, active dental problems within 4 weeks of registration, including
             infection of the teeth or jawbone (maxilla or mandible); dental or fixture trauma;
             current or prior diagnosis of osteonecrosis of the jaw (ONJ); exposed bone in the
             mouth; or slow healing after dental procedures; 6.3 Dental surgery (e.g., extractions,
             implants) within 6 weeks of study entry and while receiving study treatment; for
             patients who require dental surgery, there are no data to suggest whether
             discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the
             jaw (ONJ) [see Section 7.2.4].

             6.4 Acquired Immune Deficiency Syndrome (AIDS) based upon current Center for Disease
             Control (CDC) definition; note, however, that HIV testing is not required for entry
             into this protocol. The need to exclude patients with AIDS from this protocol is
             necessary because the treatments involved in this protocol may be significantly
             immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised
             patients.

          7. Pregnant or lactating patients are excluded, as treatment may be harmful to embryos
             and/or nursing infants.