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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: November 3, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Lung Cancer
Metastatic Cancer
Pain
Prostate Cancer
Dietary Supplement: Calcium
Dietary Supplement: Vitamin D
Drug: zoledronic acid
Drug: Sm-153
Radiation: Sr-89
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases From Lung, Breast, and Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Time to Development of a Malignant Skeletal-related Events (SRE) [ Time Frame: From randomization to date of SRE development ] [ Designated as safety issue: No ]
    Median Time to development of a malignant skeletal related event (SRE), which is defined as a pathological bone fracture, spinal cord compression, surgery to bone or radiation to bone is estimated using Kaplan-Meier method. The time of failure was measured from date of date of randomization to the date of a documented SRE. The analysis was planned to occur after 257 SRE have been observed, unless the criteria for early stopping are met.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 261
Study Start Date: July 2006
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Zoledronic acid
Zoledronic acid, vitamin D and calcium supplements.
Dietary Supplement: Calcium
At least 500 mg of calcium (1 pill) by mouth daily until the study doctor thinks it is in their best interest to stop.
Dietary Supplement: Vitamin D
400 IU of vitamin D (1 pill) by mouth daily until the study doctor thinks it is in their best interest to stop.
Drug: zoledronic acid
4 mg of Zoledronic acid intravenously once a month until the study doctor thinks it is in their best interest to stop.
Other Name: Zometa
Experimental: Zoledronic acid + Radopharmaceuticals
Zoledronic acid, vitamin D and calcium supplements, plus Sr-89 or Sm-153.
Dietary Supplement: Calcium
At least 500 mg of calcium (1 pill) by mouth daily until the study doctor thinks it is in their best interest to stop.
Drug: zoledronic acid
4 mg of Zoledronic acid intravenously once a month until the study doctor thinks it is in their best interest to stop.
Other Name: Zometa
Drug: Sm-153
Single dose intravenously 1 mCi/kg body weight.
Other Name: Samarium-153
Radiation: Sr-89
Single dose intravenously 4 mCi.
Other Name: Strontium-89

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00365105

  Show 147 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: Michael J. Seider, MD, PhD, FACR Summa Center for Cancer Care at Akron City Hospital
  More Information

Additional Information:
Publications:
Seider MJ, Shook S, Langer CJ, et al.: Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: report of RTOG 0517. [Abstract] J Clin Oncol 30 (Suppl 15): A-TPS9150, 2012.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00365105     History of Changes
Other Study ID Numbers: RTOG 0517, CDR0000491233, NCI-2009-00727
Study First Received: August 16, 2006
Results First Received: November 3, 2014
Last Updated: November 3, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
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

Additional relevant MeSH terms:
Breast Neoplasms
Lung Neoplasms
Neoplasm Metastasis
Prostatic Neoplasms
Breast Diseases
Genital Diseases, Male
Genital Neoplasms, Male
Lung Diseases
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Prostatic Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Skin Diseases
Thoracic Neoplasms
Urogenital Neoplasms
Calcium, Dietary
Diphosphonates
Ergocalciferols
Vitamin D
Vitamins
Zoledronic acid
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014