Pilot Study of Bone Mineral Density Changes During Anti-PD-1 Immunotherapy

NCT07555210 | Recruiting FDA Device

• 2 other identifiers: VICCMD25019#242079
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and work by blocking protein interactions that normally prevent the immune system from recognizing and destroying cancer cells. However, these agents, now approved for over 15 types of cancers and for both early-stage and metastatic disease, are capable of causing inflammation in any organ system of the body that can lead to organ damage, dysfunction, and even death in rare cases. Some patients may suffer acute and treatable complications like joint pain, but some may have irreversible complications like hypothyroidism that requires daily, life-long medication. It is therefore important to fully understand the different types of damage ICIs can cause to better monitor patients receiving ICI therapy. A rising concern from recent reports in the literature is that ICIs may weaken bone and increase the risk of fractures. In this study, the investigators aim to characterize how ICIs impact the bone by examining several factors in patients undergoing curative-intent ICI treatment either alone or in combination with chemotherapy: bone mineral density, bone volume, and markers of bone turnover in the blood. The study will use two imaging techniques to assess bone mineral density and volume. DXA (dual X-ray absorptiometry) imaging uses low-dose X-rays to measure how dense (or strong) bones are and is often used to diagnose or assess the risk of osteoporosis. High-resolution peripheral quantitative computed tomography (HRpQCT) is a 3D imaging technology that can quantify bone structure and volume and offers high resolution that can be used to assess bone in smaller bones of the peripheral skeleton. The investigators hypothesize that ICI treatment will weaken bones and increase the risk of fractures. As ICI therapy is relatively new, a rising number of patients may be at risk of fractures or have low bone density that is not being monitored because there are no guidelines in place notifying physicians of this potential risk to patients. This is study will provide important preliminary data that will be the basis for larger studies in the future aiming to better monitor and potentially treat bone weakening in patients treated with ICIs to reduce the pain, inconvenience, and complications from fragility fractures.

Conditions

Breast Cancer (Triple Negative Breast Cancer (TNBC)); MSI-H/dMMR Rectal Cancer; Invasive Mammary Carcinoma; Classic Hodgkin Lymphoma; Renal Cell Carcinoma (Kidney Cancer); Melanoma (Skin Cancer); Non-Small Cell Lung Cancer; Squamous Cell Carcinoma Mouth

Outcome Measures

Primary Outcomes (1)

• Change in BMD using DXA

  Assess changes in BMD on DXA scans in patients undergoing anti-PD-1 therapy over the course of a year.

  At 12 months after starting immunotherapy

Secondary Outcomes (3)

• Change in plasma markers of bone resorption and formation

  At 12 months after starting immunotherapy

• Fracture incidence

  To be completed within 30 days of the end of study (12 months +/-30 days)

• Rates of documented immune-related adverse events (irAE)

  To be completed within 30 days of the end of study (12 months +/-30 days)

Other Outcomes (1)

• Bone microarchitecture using HRpQCT

  At 12 months after starting immunotherapy

Study Arms (1)

Bone mineral density scans (DXA and HRpQCT)

EXPERIMENTAL

Patients undergo two research bone mineral density scans (DXA and HRpQCT) at three time points: baseline, 4-6 months during immunotherapy, and after 12 months of immunotherapy

Device: Dual-Energy X-ray Absorptiometry (DXA); Device: High Resolution peripheral Quantitative Computed Tomography (HRpQCT)

Interventions

Dual-Energy X-ray Absorptiometry (DXA) DEVICE

Research participants undergo both DXA scans at baseline (within 1 month of starting immunotherapy), 4-6 months after starting immunotherapy, and after 12 months of immunotherapy

Bone mineral density scans (DXA and HRpQCT)

High Resolution peripheral Quantitative Computed Tomography (HRpQCT) DEVICE

Research participants undergo both HRpQCT scans at baseline (within 1 month of starting immunotherapy), 4-6 months after starting immunotherapy, and after 12 months of immunotherapy

Bone mineral density scans (DXA and HRpQCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Patients planning to start or within the first four weeks of treatment with anti-PD-1 immune checkpoint inhibitor therapy either alone or in combination with chemotherapy for curative intent for a known cancer diagnosis (use of immunotherapy must be FDA-approved and not experimental).
• Life expectancy of at least 12 months per the discretion of the treating physician.

You may not qualify if:

• Patients ineligible for anti-PD-1 therapy.
• Patients with metastatic disease.
• Patients planning treatment with dual immune checkpoint inhibitor therapy.
• Bony fractures in the pelvis, bilateral hips/femurs, thoracic spine, or lumbar spine.
• Known osteoporosis or osteopenia.
• Planned or previous treatment with denosumab, zoledronic acid, or other bisphosphonate therapy in the last six months.
• Parathyroid gland disorders, rheumatoid arthritis (unless well-controlled off active biologic therapy without chronic steroid use), CKD stage IV/V, or ESRD.
• Inability to comply with study procedures.
• Inability to lie flat for 20-25 minutes during an imaging session.
• Pregnant or breastfeeding patients.
• Medical or psychiatric co-morbidities that, in the opinion of the treating physician, would prevent the patient from successfully participating in the study.

Sponsors & Collaborators

• Jessica Mezzanotte Sharpe: lead

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Renal Cell; Kidney Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Central Study Contacts

Jessica Sharpe, MD, PhD

CONTACT

615-936-8422; jessica.m.sharpe@vumc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 29, 2026
• Study Start: August 25, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)