Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

Primary

1. Compare the efficacy of zoledronate, vitamin D, and calcium with or without strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium, in terms of preventing or delaying the time to development of malignant skeletal-related events (SREs) (defined as a pathological bone fracture, spinal cord compression, surgery to bone, or radiation to bone) in patients with bone metastases secondary to prostate, lung, or breast cancer.

Secondary

1. Compare the rate of SREs at 1 year in patients treated with these regimens.
2. Compare overall survival of patients treated with these regimens.
3. Compare quality of life of patients treated with these regimens.
4. Compare the effect of these regimens on pain control in these patients.
5. Evaluate resource utilization and cost effectiveness of these regimens.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed lung, breast, or prostate cancer

• Bone metastases, meeting both of the following criteria:
  • Must be visible on bone scan performed within the past 4 weeks
  • No painful bone metastases unless successfully treated (i.e., by external-beam irradiation) prior to study entry AND the patient has stable pain* for at least 2 weeks after that treatment

   [Note: *Stable pain is defined as a patient response of 1, 2, or 3 on Questions 4 and 5 of The Brief Pain Inventory (BPI)]

• No untreated or symptomatic brain metastases

• No spinal cord compression

• Hormone receptor status not specified

Prior/Concurrent Therapy:

• See Disease Characteristics
• Prior oral bisphosphonate therapy (i.e. alendronate sodium or similar) allowed
  • No prior IV bisphosphonates for a treatment duration of > 6 months
• At least 2 weeks since prior calcitonin, mithramycin, or gallium nitrate
• At least 2 weeks since prior external-beam radiotherapy
• At least 6 weeks since prior and no concurrent dental surgery (e.g., extractions or implants)
• No prior radioisotope therapy for bone metastasis
• Concurrent systemic chemotherapy* or hormonal therapy allowed
  • Chemotherapy and/or hormonal therapy should not be changed within 14 days prior to start of protocol treatment (arm I)
• No other concurrent bisphosphonate

 [Note: *Chemotherapy must be held 2 weeks before and for at least 2 weeks after radiopharmaceutical administration (arm II)]

Patient Characteristics:

• Zubrod performance status (PS) 0-2 (for patients with primary breast or prostate cancer) OR Zubrod PS 0-1 (for patients with primary lung cancer)
• WBC ≥ 2,400/mm³
• Absolute neutrophil count ≥ 1,800/mm³
• Platelet count ≥ 60,000/mm³
• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
• Creatinine < 3.0 mg/dL
• Bilirubin < 2.5 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled congestive heart failure within the past 6 months
• No hypertension refractory to treatment within the past 6 months
• No symptomatic coronary artery disease within the past 6 months
• No current, active dental problems within the past 4 weeks, including any of the following:
  • Infection of the teeth or jawbone (maxilla or mandible)
  • Dental or fixture trauma
  • Prior or current diagnosis of osteonecrosis of the jaw
  • Exposed bone in the mouth
  • Slow healing after dental procedures
• No known AIDS
  • HIV testing is not required

Expected Enrollment

A total of 352 patients will be accrued for this study.

Outcomes

Time to development of a malignant skeletal-related events (SRE)

SRE rate at 1 year
Overall survival
Changes in quality of life as measured by FACT-G
Changes in pain control as measured by Brief Pain Inventory (BPI)
Utility and cost effectiveness of the use of radiopharmaceuticals and bisphosphonates as measured by the EuroQol-5 Dimension (EQ-5D)

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to primary disease site (prostate vs breast vs lung) and number of bone metastases (≤ 2 vs > 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive zoledronate IV over 15 minutes once a month. Patients also receive oral vitamin D and oral calcium once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive zoledronate, vitamin D, and calcium as in arm I. Within 6 weeks of beginning study treatment, patients also receive a single dose of either strontium chloride Sr 89 IV or samarium Sm 153 lexidronam pentasodium IV.

Quality of life and pain are assessed at baseline and then at 1, 3, 6, and 12 months from start of protocol treatment.

After completion of study treatment, patients are followed every 6 months.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Michael Seider, MD, PhD, FACR, Protocol chair		Ph: 330-375-3557 Email: seiderm@summa-health.org

Registry Information
Official Title		Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases from Lung, Breast, and Prostate Cancer
Trial Start Date		2006-07-11
Trial Completion Date		2013-03-31 (estimated)
Registered in ClinicalTrials.gov		NCT00365105
Date Submitted to PDQ		2006-06-05
Information Last Verified		2011-02-24
NCI Grant/Contract Number		CA37422

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