Lung Neoplasm
Conditions
Brief summary
This is a double blind randomized controlled study investigating the efficacy of a single dose of 150 mg risedronate (a bone anti-resorptive) vs a single dose of placebo given prior to SBRT for peripheral lung tumors that are within 2 cm of the chest wall. Our hypothesis is that the use of a single dose of 150 mg risedronate will eliminate or greatly reduce the rapid bone loss that occurs with radiation induced early osteoclast recruitment/activation. Patients will be given either a single dose of 150 mg risedronate or placebo at the time of their treatment mapping "simulation" CT scan. Typically, radiation treatments begin at 1 - 3 weeks following this mapping scan, as each treatment plan requires detailed physics calculations and quality assurance checks. All CT imaging referenced below is performed as a routine standard of care surveillance and is necessary for cancer treatment follow-up. These chest CT scans that are utilized in this research protocol would be performed every 3 months regardless of inclusion on this trial.
Detailed description
2.1 Primary Objective(s) The primary objective is to assess the percent change in bone mean cortical thickness within regions of bone receiving 30 Gy or more at 3 months after SBRT. The % change in mean cortical thickness will be compared between patients who received risedronate and those who received placebo. 2.2 Secondary Objective(s) In addition to the primary objective, the investigators will further analyze the remaining routine follow-up chest CT scans, for mean cortical thickness change in regions of bone that received 0 - 10 Gy, \>10 - 20 Gy, \> 20 - 30 Gy, \> 30 - 40 Gy, and \> 40 Gy at all time points including 3 months, 6 months, 9 months, and 12 months. These scans are standard of care and would be performed regardless of inclusion on this trial. This will allow us to determine the potential persistence of effects from SBRT and bisphosphonate use. The investigators will assess and compare the incidence and grade (per modified CTCAE v.5) of radiation induced chest wall pain within the radiation treatment portal (within the 50% isodose line) at time of each routine follow up visit (3 months, 6 months, 9 months, and 12 months post SBRT). The purpose of utilizing a placebo and double-blind design is that chest wall pain is a subjective finding. Furthermore, it is unclear if chest wall pain from radiation is directly due to bone damage, nerve damage, muscle irritation, or a combination of all of these factors. The use of placebo will help us reduce the potential for bias in pain assessment. The investigators will assess and compare the incidence of rib and vertebral fractures (as noted on CT imaging) that occur within 12 months of irradiation and are within the radiation treatment field. The radiation treatment field will be defined as within the 50% isodose line. The urine concentration of an osteoclast-specific biomarker, urinary N-telopeptide (NTX) indicating osteoclast activity will be assessed prior to SBRT and at each routine follow up visit (at 3 months, 6 months, 9 months, and 12 months post SBRT).
Interventions
DRUGrisedronate
Risedronate 150 mg Oral Given once 7 - 21 days prior to initiation of SBRT
DRUGMatching placebo
Dose not applicable, given once 7-21 days prior to initiation of SBRT
Sponsors
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be 18 years or older, but there is no upper limit on age of inclusion. * Patients must have a peripheral lung tumor that is amenable to SBRT as determined by the treating radiation oncologist. To be classified as a peripheral lung tumor, the tumor edge (the edge of the gross tumor volume or GTV in radiation treatment planning software) must be within 2 cm of the chest wall. This is determined by the treating radiation oncologist. The chest wall is defined as the chest wall musculature or ribs/vertebrae immediately adjacent to the lungs. * Patients must have ECOG status of 0-3 * Patients must have a life expectancy of at least 3 months as determined by the treating radiation oncologist. * Patients must have the ability to understand and the willingness to sign an IRB-approved informed consent document.
Exclusion criteria
Prior radiation to any part of the body including the lungs or thorax is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Mean Cortical Thickness | At baseline and at 3 months post radiation | The primary outcome measure is the percent change in mean cortical thickness (C.Th) of bones receiving 30 Gy or more at 3 months post SBRT, when compared to pre-SBRT cortical thickness |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | At baseline, 3 months, 6 months, 9 months and 12 months post radiation | The percent change in mean C.Th of bones will be assessed in regions of bone that received 0 - 10 Gy, \>10 - 20 Gy, \> 20 - 30 Gy, \> 30 - 40 Gy, and \> 40 Gy at all time points including 3 months, 6 months, 9 months, and 12 months. |
| Number of Participants With Chest Wall Pain | At baseline, 3 months, 6 months, 9 months and 12 months post radiation | Chest wall pain incidence and grade will be collected as per modified CTCAE v. 5 within the within the 50% isodose line. Appendix K. Below we report numbers with any chest wall pain of grades 3+ over the year of followup. |
| Number of Participants With Rib and Vertebral Fracture | At 12 months post radiation | Incidence of rib and vertebral fractures (as noted on CT imaging) that occur within 12 months of irradiation and are within the within 50% isodose line. |
| Urine Concentration at 4 Time Points | At 3 months, 6 months, 9 months and 12 months post radiation | The urine concentration of an osteoclast-specific biomarker, urinary N-telopeptide (U-NTX) indicating osteoclastic activity will be assessed prior to SBRT and at each routine follow up visit (at 3 months, 6 months, 9 months, and 12 months post SBRT). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichael Farris, MD
Wake Forest University Health Sciences
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Risedronate Risedronate 150 mg given once 7-21 days prior to initiation of SBRT
risedronate: Risedronate 150 mg Oral Given once 7 - 21 days prior to initiation of SBRT | 41 |
| Matching Placebo Matching placebo, dose not applicable given once 7-21 days prior to initiation of SBRT
Matching placebo: Dose not applicable, given once 7-21 days prior to initiation of SBRT | 43 |
| Total | 84 |
Baseline characteristics
| Characteristic | Risedronate | Total | Matching Placebo |
|---|---|---|---|
| Age, Continuous | 71.4 years STANDARD_DEVIATION 7.9 | 71.2 years STANDARD_DEVIATION 7.6 | 71.1 years STANDARD_DEVIATION 7.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 82 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 37 Participants | 76 Participants | 39 Participants |
| Region of Enrollment United States | 41 participants | 84 participants | 43 participants |
| Sex: Female, Male Female | 16 Participants | 34 Participants | 18 Participants |
| Sex: Female, Male Male | 25 Participants | 50 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 1 / 43 |
| other Total, other adverse events | 5 / 41 | 0 / 43 |
| serious Total, serious adverse events | 0 / 41 | 2 / 43 |
Outcome results
Primary
Changes in Mean Cortical Thickness
The primary outcome measure is the percent change in mean cortical thickness (C.Th) of bones receiving 30 Gy or more at 3 months post SBRT, when compared to pre-SBRT cortical thickness
Time frame: At baseline and at 3 months post radiation
Population: A small number of participants who were enrolled were not able to have cortical thickness determined at 3 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risedronate | Changes in Mean Cortical Thickness | 4.24 percent change in mm cortical thickne | Standard Error 3.04 |
| Matching Placebo | Changes in Mean Cortical Thickness | 7.14 percent change in mm cortical thickne | Standard Error 2.93 |
Secondary
4 Time Points Assessing Change in Mean Cortical Thickness of Bones
The percent change in mean C.Th of bones will be assessed in regions of bone that received 0 - 10 Gy, \>10 - 20 Gy, \> 20 - 30 Gy, \> 30 - 40 Gy, and \> 40 Gy at all time points including 3 months, 6 months, 9 months, and 12 months.
Time frame: At baseline, 3 months, 6 months, 9 months and 12 months post radiation
Population: A small number of participants did not have follow-up cortical thickness measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 10-20 Gy--time 9mo to bl | 7.71 percent change in mm cortical thickness | Standard Error 2.95 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region <10 Gy--time 6mo to bl | 10.37 percent change in mm cortical thickness | Standard Error 2.63 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region <10 Gy--time 9mo to bl | 12.10 percent change in mm cortical thickness | Standard Error 2.71 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region <10 Gy--time 12mo to bl | 11.58 percent change in mm cortical thickness | Standard Error 2.89 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 10-20 Gy--time 3mo to bl | 9.27 percent change in mm cortical thickness | Standard Error 2.78 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 10-20 Gy--time 6mo to bl | 6.24 percent change in mm cortical thickness | Standard Error 2.86 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region <10 Gy--time 3mo to bl | 13.04 percent change in mm cortical thickness | Standard Error 2.56 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 10-20 Gy--time 12mo to bl | 10.11 percent change in mm cortical thickness | Standard Error 3.14 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 20-30 Gy--time 3mo to bl | 8.40 percent change in mm cortical thickness | Standard Error 2.99 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 20-30 Gy--time 6mo to bl | 5.41 percent change in mm cortical thickness | Standard Error 3.08 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 20-30 Gy--time 9mo to bl | 6.48 percent change in mm cortical thickness | Standard Error 3.18 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 20-30 Gy--time12mo to bl | 7.42 percent change in mm cortical thickness | Standard Error 3.36 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 30-40 Gy--time 3mo to bl | 4.90 percent change in mm cortical thickness | Standard Error 3.22 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 30-40 Gy--time 6mo to bl | 1.98 percent change in mm cortical thickness | Standard Error 3.31 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 30-40 Gy--time 9mo to bl | 3.70 percent change in mm cortical thickness | Standard Error 3.43 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 30-40 Gy--time12mo to bl | 2.23 percent change in mm cortical thickness | Standard Error 3.62 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >30 Gy--time 3mo to bl | 4.24 percent change in mm cortical thickness | Standard Error 3.04 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >30 Gy--time 6mo to bl | 1.66 percent change in mm cortical thickness | Standard Error 3.13 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >30 Gy--time 9mo to bl | 2.12 percent change in mm cortical thickness | Standard Error 3.24 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >30 Gy--time 12mo to bl | -0.42 percent change in mm cortical thickness | Standard Error 3.42 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >40 Gy--time 3mo to bl | 5.83 percent change in mm cortical thickness | Standard Error 8.1 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >40 Gy--time 6mo to bl | 5.62 percent change in mm cortical thickness | Standard Error 8.41 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >40 Gy--time 9mo to bl | 6.03 percent change in mm cortical thickness | Standard Error 8.53 |
| Risedronate | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >40 Gy--time 12mo to bl | -1.44 percent change in mm cortical thickness | Standard Error 8.92 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >40 Gy--time 9mo to bl | 21.37 percent change in mm cortical thickness | Standard Error 7.69 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region <10 Gy--time 3mo to bl | 5.57 percent change in mm cortical thickness | Standard Error 2.5 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 30-40 Gy--time 3mo to bl | 5.20 percent change in mm cortical thickness | Standard Error 3.1 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region <10 Gy--time 6mo to bl | 5.76 percent change in mm cortical thickness | Standard Error 2.57 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >30 Gy--time 9mo to bl | 10.32 percent change in mm cortical thickness | Standard Error 3.02 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region <10 Gy--time 9mo to bl | 8.07 percent change in mm cortical thickness | Standard Error 2.59 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 30-40 Gy--time 6mo to bl | 3.21 percent change in mm cortical thickness | Standard Error 3.19 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region <10 Gy--time 12mo to bl | 9.42 percent change in mm cortical thickness | Standard Error 2.7 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >40 Gy--time 6mo to bl | 20.30 percent change in mm cortical thickness | Standard Error 7.68 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 10-20 Gy--time 3mo to bl | 4.97 percent change in mm cortical thickness | Standard Error 2.72 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 30-40 Gy--time 9mo to bl | 9.64 percent change in mm cortical thickness | Standard Error 3.19 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 10-20 Gy--time 6mo to bl | 3.95 percent change in mm cortical thickness | Standard Error 2.82 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >30 Gy--time 12mo to bl | 11.72 percent change in mm cortical thickness | Standard Error 3.14 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 10-20 Gy--time 9mo to bl | 5.65 percent change in mm cortical thickness | Standard Error 2.82 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 30-40 Gy--time12mo to bl | 11.77 percent change in mm cortical thickness | Standard Error 3.32 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 10-20 Gy--time 12mo to bl | 7.30 percent change in mm cortical thickness | Standard Error 2.94 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >40 Gy--time 12mo to bl | 17.17 percent change in mm cortical thickness | Standard Error 8.25 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 20-30 Gy--time 3mo to bl | 3.70 percent change in mm cortical thickness | Standard Error 2.87 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >30 Gy--time 3mo to bl | 7.14 percent change in mm cortical thickness | Standard Error 2.93 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 20-30 Gy--time 6mo to bl | 0.10 percent change in mm cortical thickness | Standard Error 2.95 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >40 Gy--time 3mo to bl | 12.82 percent change in mm cortical thickness | Standard Error 7.53 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 20-30 Gy--time 9mo to bl | 4.94 percent change in mm cortical thickness | Standard Error 2.95 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region >30 Gy--time 6mo to bl | 6.11 percent change in mm cortical thickness | Standard Error 3.01 |
| Matching Placebo | 4 Time Points Assessing Change in Mean Cortical Thickness of Bones | % change cort thickness in region 20-30 Gy--time12mo to bl | 7.23 percent change in mm cortical thickness | Standard Error 3.08 |
Secondary
Number of Participants With Chest Wall Pain
Chest wall pain incidence and grade will be collected as per modified CTCAE v. 5 within the within the 50% isodose line. Appendix K. Below we report numbers with any chest wall pain of grades 3+ over the year of followup.
Time frame: At baseline, 3 months, 6 months, 9 months and 12 months post radiation
Population: Some participants did not have sufficient self-reported symptom pain data to determine if, over course of 12 months, they had any chest wall pain of grade 3 or higher
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Risedronate | Number of Participants With Chest Wall Pain | 2 Participants |
| Matching Placebo | Number of Participants With Chest Wall Pain | 4 Participants |
Secondary
Number of Participants With Rib and Vertebral Fracture
Incidence of rib and vertebral fractures (as noted on CT imaging) that occur within 12 months of irradiation and are within the within 50% isodose line.
Time frame: At 12 months post radiation
Population: For a small number of participants it was not possible to determine clearly if a fracture had occurred within 12 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Risedronate | Number of Participants With Rib and Vertebral Fracture | 15 Participants |
| Matching Placebo | Number of Participants With Rib and Vertebral Fracture | 11 Participants |
Secondary
Urine Concentration at 4 Time Points
The urine concentration of an osteoclast-specific biomarker, urinary N-telopeptide (U-NTX) indicating osteoclastic activity will be assessed prior to SBRT and at each routine follow up visit (at 3 months, 6 months, 9 months, and 12 months post SBRT).
Time frame: At 3 months, 6 months, 9 months and 12 months post radiation
Population: A small number of participants did not have urine samples analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Risedronate | Urine Concentration at 4 Time Points | Urinary NTX values at 3mo | 460.2 pg/mL | Standard Deviation 514.1 |
| Risedronate | Urine Concentration at 4 Time Points | Urinary NTX values at 9mo | 536.1 pg/mL | Standard Deviation 460 |
| Risedronate | Urine Concentration at 4 Time Points | Urinary NTX values at 6mo | 669.9 pg/mL | Standard Deviation 955.9 |
| Risedronate | Urine Concentration at 4 Time Points | Urinary NTX values at 12mo | 611.0 pg/mL | Standard Deviation 494.7 |
| Risedronate | Urine Concentration at 4 Time Points | Urinary NTX values at BL | 499.3 pg/mL | Standard Deviation 592 |
| Matching Placebo | Urine Concentration at 4 Time Points | Urinary NTX values at 12mo | 411.7 pg/mL | Standard Deviation 314 |
| Matching Placebo | Urine Concentration at 4 Time Points | Urinary NTX values at BL | 524.9 pg/mL | Standard Deviation 399.4 |
| Matching Placebo | Urine Concentration at 4 Time Points | Urinary NTX values at 3mo | 494.5 pg/mL | Standard Deviation 342.4 |
| Matching Placebo | Urine Concentration at 4 Time Points | Urinary NTX values at 6mo | 350.7 pg/mL | Standard Deviation 301.8 |
| Matching Placebo | Urine Concentration at 4 Time Points | Urinary NTX values at 9mo | 507.0 pg/mL | Standard Deviation 492.2 |