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Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT

Primary Purpose

Lung Neoplasm

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

risedronate

Matching placebo

About this trial

This is an interventional treatment trial for Lung Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

High Point Regional Medical Center
Wake Forest Baptist Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Risedronate

Matching Placebo

Arm Description

Risedronate 150 mg 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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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.

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.

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).

Full Information

NCT ID

NCT03861091

First Posted

February 28, 2019

Last Updated

July 24, 2023

Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03861091

Brief Title

Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

July 12, 2019 (Actual)

Primary Completion Date

March 2, 2022 (Actual)

Study Completion Date

March 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Neoplasm

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

84 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Risedronate

Arm Type

Experimental

Arm Description

Risedronate 150 mg given once 7-21 days prior to initiation of SBRT

Arm Title

Matching Placebo

Arm Type

Placebo Comparator

Arm Description

Matching placebo, dose not applicable given once 7-21 days prior to initiation of SBRT

Intervention Type

Drug

Intervention Name(s)

risedronate

Other Intervention Name(s)

Actonel, Atelvia

Intervention Description

Risedronate 150 mg Oral Given once 7 - 21 days prior to initiation of SBRT

Intervention Type

Drug

Intervention Name(s)

Matching placebo

Intervention Description

Dose not applicable, given once 7-21 days prior to initiation of SBRT

Primary Outcome Measure Information:

Title

Changes in Mean Cortical Thickness

Description

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

Secondary Outcome Measure Information:

Title

4 Time Points Assessing Change in Mean Cortical Thickness of Bones

Description

Time Frame

At baseline, 3 months, 6 months, 9 months and 12 months post radiation

Title

Number of Participants With Chest Wall Pain

Description

Time Frame

At baseline, 3 months, 6 months, 9 months and 12 months post radiation

Title

Number of Participants With Rib and Vertebral Fracture

Description

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

Title

Urine Concentration at 4 Time Points

Description

Time Frame

At 3 months, 6 months, 9 months and 12 months post radiation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Farris, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

High Point Regional Medical Center

City

High Point

State/Province

North Carolina

ZIP/Postal Code

27262

Country

United States

Facility Name

Wake Forest Baptist Comprehensive Cancer Center

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT

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