A Phase 3 interventional study of Calcium and Vitamin D in Breast Cancer, Lung Cancer and Metastatic Cancer, sponsored by Radiation Therapy Oncology Group. Completed at 147 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-20.
Sponsored by Radiation Therapy Oncology Group · Phase 3, Interventional, and Supportive care
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
Secondary
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.
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.
12,815 studies on the registry are indexed under Breast Neoplasms; 2,920 are open to participants now.
This study's enrollment of 261 is above the median of 72 across 9,494 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Radiation Therapy Oncology Group is the lead sponsor of 155 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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:
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;
Exclusion Criteria
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.
Zoledronic acid, vitamin D and calcium supplements.
Dietary Supplement: Calcium · Dietary Supplement: Vitamin D · Drug: zoledronic acid
Zoledronic acid, vitamin D and calcium supplements, plus Sr-89 or Sm-153.
Dietary Supplement: Calcium · Drug: zoledronic acid · Drug: Sm-153 · Radiation: Sr-89
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.
Also known as: Zometa
Single dose intravenously 1 mCi/kg body weight.
Also known as: Samarium-153
Single dose intravenously 4 mCi.
Also known as: Strontium-89
Time to Development of a Malignant Skeletal-related Events (SRE)
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 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.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 80.1 months.
Number of Patients Experiencing a Skeletal-related Event (SRE) Within One Year
Skeletal-related events are defined as a pathological bone fracture, spinal cord compression, surgery to bone or radiation to bone.
Time frame: From randomization to 1 year
Overall Survival
Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 101.7 months.
Change in Functional Assessment of Cancer Therapy - General (FACT-G) at One Year
The FACT-G is a validated 27-item measure in which a higher score represents higher quality of life (QOL). Physical, functional, social and emotional well-being subscale scores are added together to form the FACT-G total score. Responses range from 0=Not a lot to 4=Very much. Certain items must be reversed before being added, by subtracting the response from 4. Subscale items are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Total score ranges from 0-108; physical, social and functional subscales from 0-28; emotional subscale from 0-24. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing the subscale scores can be prorated. Change score at one year is calculated as one year score - baseline score with a positive change score indicating improvement in QOL.
Time frame: Baseline and 1 year
Change in Brief Pain Inventory (BPI) at One Year
The Brief Pain Inventory (BPI) is a measurement tool for assessing clinical pain. The BPI assesses severity (pain at its "worst," "least," "average," and "now"), and interference (how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Patients rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function on a scale of 0 to 10, with 0=no pain/interference and 10=interferes completely/worst pain imaginable.
Time frame: Baseline and 1 year
Change in EuroQol-5 Dimension 3-level (EQ-5D-3L) at One Year
The EQ-5D-3L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Change at one year is calculated as one-year score - baseline score with positive change indicating improved quality of life.
Time frame: Baseline and 1 year
| Milestone | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| Started | 129 | 132 |
| Eligible | 124 | 124 |
| Eligible with adverse event data | 123 | 124 |
| Completed | 124 | 124 |
| Not completed | 5 | 8 |
| Withdrew: Protocol violation | 5 | 8 |
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 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.
| months | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| Time to Development of a Malignant Skeletal-related Events (SRE) | 29.9 (25.8 to 37.4) | 27.4 (21.2 to 35.34) |
Skeletal-related events are defined as a pathological bone fracture, spinal cord compression, surgery to bone or radiation to bone.
| Participants | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| Number of Patients Experiencing a Skeletal-related Event (SRE) Within One Year | 28 | 20 |
Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
| months | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| Overall Survival | 32.1 (22.1 to 37.5) | 26.9 (20.4 to 33.6) |
The FACT-G is a validated 27-item measure in which a higher score represents higher quality of life (QOL). Physical, functional, social and emotional well-being subscale scores are added together to form the FACT-G total score. Responses range from 0=Not a lot to 4=Very much. Certain items must be reversed before being added, by subtracting the response from 4. Subscale items are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Total score ranges from 0-108; physical, social and functional subscales from 0-28; emotional subscale from 0-24. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing the subscale scores can be prorated. Change score at one year is calculated as one year score - baseline score with a positive change score indicating improvement in QOL.
| units on a scale | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| FACT-G Total | -1 (-8 to 5) | -2 (-11 to 4) |
| Physical Well-Being | -1 (-4 to 1) | -1 (-4 to 2) |
| Social/Family Well-Being | 0 (-1 to 2) | 0 (-2 to 2) |
| Emotional Well-Being | 0 (-1 to 3) | 0 (-2 to 2) |
| Functional Well-Being | 0 (-4 to 2) | 0 (-4 to 1) |
The Brief Pain Inventory (BPI) is a measurement tool for assessing clinical pain. The BPI assesses severity (pain at its "worst," "least," "average," and "now"), and interference (how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Patients rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function on a scale of 0 to 10, with 0=no pain/interference and 10=interferes completely/worst pain imaginable.
| units on a scale | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| Change in Brief Pain Inventory (BPI) at One Year | 1 (-5 to 9) | 0 (-6 to 7) |
The EQ-5D-3L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Change at one year is calculated as one-year score - baseline score with positive change indicating improved quality of life.
| units on a scale | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| Index Score | -0.04 ± 0.14 | -0.06 ± 0.15 |
| VAS Score | -1.20 ± 20.43 | -6.70 ± 15.70 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Zoledronic Acid | — | 31/123 (25.2%) | 102/123 (82.9%) |
| Zoledronic Acid + Radiopharmaceuticals | — | 37/124 (29.8%) | 108/124 (87.1%) |
| Event | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| HemoglobinBlood and lymphatic system disorders | 6/123 | 10/124 |
| Platelet count decreasedInvestigations | 1/123 | 7/124 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 5/123 | 3/124 |
| Pneumonitis NOSRespiratory, thoracic and mediastinal disorders | 5/123 | 2/124 |
| Hypotension NOSVascular disorders | 5/123 | 2/124 |
| FatigueGeneral disorders | 4/123 | 0/124 |
| Blood creatinine increasedInvestigations | 4/123 | 3/124 |
| DehydrationMetabolism and nutrition disorders | 4/123 | 4/124 |
| Disease progression NOSGeneral disorders | 3/123 | 2/124 |
| DizzinessNervous system disorders | 3/123 | 0/124 |
| Event | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals |
|---|---|---|
| FatigueGeneral disorders | 68/123 | 77/124 |
| HemoglobinBlood and lymphatic system disorders | 56/123 | 73/124 |
| Platelet count decreasedInvestigations | 19/123 | 52/124 |
| Bone painMusculoskeletal and connective tissue disorders | 40/123 | 46/124 |
| Leukopenia NOSInvestigations | 26/123 | 42/124 |
| Back painMusculoskeletal and connective tissue disorders | 39/123 | 37/124 |
| Hyperglycaemia NOSMetabolism and nutrition disorders | 38/123 | 32/124 |
| Neutrophil countInvestigations | 15/123 | 32/124 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 26/123 | 32/124 |
| Blood alkaline phosphatase increasedInvestigations | 31/123 | 27/124 |
Eligible patients
| Age, Continuous(years) | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals | Total |
|---|---|---|---|
| Median | 68 (25 to 88) | 68 (32 to 90) | 68 (25 to 90) |
| Sex: Female, Male(Participants) | Zoledronic Acid | Zoledronic Acid + Radiopharmaceuticals | Total |
|---|---|---|---|
| Female | 47 | 48 | 95 |
| Male | 77 | 76 | 153 |
Showing the first 100 of 147 sites.
Ran from Jul 2006 to primary completion in Jan 2012, 66 months.
Results were first posted in Nov 2014, 2 years 10 months after primary completion.
Of 293 non-industry phase 3 interventional studies under Breast Neoplasms, half reached primary completion within 80 months of starting (the median), counting those still running; a quarter within 50 and three quarters within 125. This study's 66 months is below that.
Counting every sponsor, half of 540 studies reached it within 58 months; a quarter within 34 and three quarters within 93.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Samarium-153
Radiation Therapy Oncology Group →