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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00365105
First received: August 16, 2006
Last updated: December 19, 2013
Last verified: December 2013

August 16, 2006
December 19, 2013
July 2006
January 2012   (final data collection date for primary outcome measure)
Time to development of a malignant skeletal-related events (SRE) [ Time Frame: From randomization to date of SRE development ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00365105 on ClinicalTrials.gov Archive Site
  • SRE rate at 1 year [ Time Frame: From randomization to 1 year ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs at the same time as the primary outcome. ] [ Designated as safety issue: No ]
  • Changes in quality of life as measured by FACT-G [ Time Frame: From pre-treatment to 1 year ] [ Designated as safety issue: No ]
  • Changes in pain control as measured by Brief Pain Inventory (BPI) [ Time Frame: From pre-treatment to 1 year ] [ Designated as safety issue: No ]
  • Utility and cost effectiveness of the use of radiopharmaceuticals and bisphosphonates as measured by the EuroQol-5 Dimension (EQ-5D) [ Time Frame: From pre-treatment to 1 year ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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
Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases From Lung, Breast, and Prostate Cancer

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.

OBJECTIVES:

Primary

  • 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

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

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.

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

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
  • Breast Cancer
  • Lung Cancer
  • Metastatic Cancer
  • Pain
  • Prostate Cancer
  • Dietary Supplement: calcium carbonate
    Zoledronic acid given IV; vitamin D and calcium given orally
  • Dietary Supplement: calcium citrate
    Zoledronic acid given IV; vitamin D and calcium given orally
  • Dietary Supplement: calcium glucarate
    Zoledronic acid given IV; vitamin D and calcium given orally
  • Dietary Supplement: vitamin D
    Zoledronic acid given IV; vitamin D and calcium given orally
  • Drug: calcium gluconate
    Zoledronic acid given IV; vitamin D and calcium given orally
  • Drug: zoledronic acid
    Zoledronic acid given IV; vitamin D and calcium given orally
  • Radiation: samarium Sm 153 lexidronam pentasodium
    Given IV
  • Radiation: strontium chloride Sr 89
    Given IV
  • Active Comparator: 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.
    Interventions:
    • Dietary Supplement: calcium carbonate
    • Dietary Supplement: calcium citrate
    • Dietary Supplement: calcium glucarate
    • Dietary Supplement: vitamin D
    • Drug: calcium gluconate
    • Drug: zoledronic acid
  • Experimental: 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.
    Interventions:
    • Dietary Supplement: calcium carbonate
    • Dietary Supplement: calcium citrate
    • Dietary Supplement: calcium glucarate
    • Dietary Supplement: vitamin D
    • Drug: calcium gluconate
    • Drug: zoledronic acid
    • Radiation: samarium Sm 153 lexidronam pentasodium
    • Radiation: strontium chloride Sr 89
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
261
Not Provided
January 2012   (final data collection date for primary outcome measure)

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

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)
  • White blood cell count (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

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00365105
RTOG 0517, CDR0000491233, NCI-2009-00727
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Study Chair: Michael J. Seider, MD, PhD, FACR Summa Center for Cancer Care at Akron City Hospital
Radiation Therapy Oncology Group
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP