Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT

NCT ID: NCT03861091

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-12
• Study Completion Date: 2022-03-02

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).

Conditions

Lung Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Risedronate

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

Group Type: EXPERIMENTAL

risedronate

Intervention Type: DRUG

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

Matching Placebo

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

Group Type: PLACEBO_COMPARATOR

Matching placebo

Intervention Type: DRUG

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

Interventions

risedronate

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

Intervention Type: DRUG

Matching placebo

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

Intervention Type: DRUG

Other Intervention Names

Actonel; Atelvia

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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Farris, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

High Point Regional Medical Center

High Point, North Carolina, United States

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

CCCWFU99518

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00056835

Identifier Type: -

Identifier Source: org_study_id