Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT

A Randomized Clinical Trial of Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT

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.

Study Overview

• Status: Completed
• Conditions: Lung Neoplasm
• Intervention / Treatment: Drug: risedronate; Drug: Matching placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • High Point Regional Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria

• Tumor edge is greater than 2 cm from the chest wall. The edge of tumor is the edge of the gross tumor volume or GTV as defined in radiation treatment planning software. This is determined by the treating radiation oncologist.
• Tumors that are expected to require more than 10 fractions of radiation as determined by the treating radiation oncologist.
• History of using bone anti-resorptive agents including bisphosphonates or RANK-L inhibitors within the last 1 year.
• Inability to stand or sit upright for at least 30 minutes, which is necessary for ingestion of risedronate.
• Hypocalcemia defined as serum total calcium lower than 8.5 mg/dL on most recent bloodwork that is within 3 months of administration of study drug/placebo.
• Severe renal impairment (EGFR <30 mL/min) on most recent bloodwork that is within 3 months of administration of study drug/placebo.
• Known allergy to risedronate or other bisphosphonates
• Surgery affecting the bone or dental operations within the last 6 months. This will be explicitly asked and documented in the EMR by treating radiation oncologist.
• Dental operations do not include routine cleaning or cavity fillings
• Dental operations that exclude patients refer to any manipulation of mandible.
• Positive urine pregnancy test in women of child bearing potential within 1 week of registration. Pregnant women are excluded from this study because radiation has clear teratogenic and potentially abortifacient risks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Risedronate; Risedronate 150 mg given once 7-21 days prior to initiation of SBRT	Drug: risedronate; Risedronate 150 mg Oral Given once 7 - 21 days prior to initiation of SBRT; Other Names: Actonel; Atelvia
Placebo Comparator: Matching Placebo; Matching placebo, dose not applicable given once 7-21 days prior to initiation of SBRT	Drug: Matching placebo; Dose not applicable, given once 7-21 days prior to initiation of SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	At baseline and at 3 months post radiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At baseline, 3 months, 6 months, 9 months and 12 months post radiation
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.	At baseline, 3 months, 6 months, 9 months and 12 months post radiation
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.	At 12 months post radiation
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).	At 3 months, 6 months, 9 months and 12 months post radiation

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michael Farris, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2019
• Primary Completion (Actual): March 2, 2022
• Study Completion (Actual): March 2, 2022

Study Registration Dates

• First Submitted: February 28, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Risedronic Acid
• Other Study ID Numbers: IRB00056835; P30CA012197 (U.S. NIH Grant/Contract); CCCWFU99518 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No