Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations.

NCT ID: NCT03958565

Last Updated: 2025-05-21

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-04-28
• Study Completion Date: 2028-04-28

Brief Summary

The purpose of this study is to assess percentage reduction in the of urine NTX and serum CTX , in patients with NSCLC and bone metastases 1) with actionable driver oncogene on standard of care (SOC) TKI at 3 months post treatment and 2) without actionable mutations on standard of care therapy (chemotherapy/immunotherapy) treated with zoledronic acid or denosumab at the same time period.

Detailed Description

This is an observational study involving two arms of NSCLC with metastatic bony disease at the time of enrollment in the study. One group will have an actionable driver oncogene and initiate treatment in any line with a TKI as standard of care and concurrent to participation to this study; expected to have an objective response rate in ≥40% who have not previously seen anti-bone resorptive therapy. The other group will not have actionable mutations and initiate treatment with chemotherapy/immunotherapy along with new onset therapy with IV zoledronic acid 4mg Q4 weeks or subcutaneous denosumab 120 mg Q12 weeks for bone disease, which is standard of care and would be concurrent to participation in this study.

Baseline and on-treatment imaging and serum total alkaline phosphatase will be performed per SOC.

Additional non-SOC bone turnover markers including , urine N-telopeptide (NTX) and serum C-terminal telopeptide (CTX), will be checked at baseline and then at 1, 3, 6, and 12 months.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Actionable driver oncogene

One group will have an actionable driver oncogene and initiate treatment in any line with a TKI as standard of care and concurrent to participation to this study; expected to have an objective response rate in ≥40% who have not previously seen anti-bone resorptive therapy.

Tyrosine Kinase Inhibitor

Intervention Type: BIOLOGICAL

Targeted therapy given as standard of care.

No Actionable Mutations

The other group will not have actionable mutations and initiate treatment with chemotherapy/immunotherapy along with new onset therapy with IV zoledronic acid 4mg Q4 weeks or subcutaneous denosumab 120 mg Q12 weeks for bone disease, which is standard of care and would be concurrent to participation in this study.

Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]

Intervention Type: DRUG

Given Q4 weeks as standard of care

Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]

Intervention Type: DRUG

Given Q12 weeks for bone disease as standard of care

Interventions

Tyrosine Kinase Inhibitor

Targeted therapy given as standard of care.

Intervention Type: BIOLOGICAL

Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]

Given Q4 weeks as standard of care

Intervention Type: DRUG

Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]

Given Q12 weeks for bone disease as standard of care

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision to sign and date the consent form

2. Stated willingness to comply with all study procedures and be available for the duration of the study

3. Be a male or female aged 18-100 years

4. Pathologically confirmed non-small cell lung cancer

5. Molecular testing through a CLIA-validated NGS assay. This can be done using either tissue based samples or blood-based samples (ctDNA)

6. ECOG PS 0-2

7. Decision to be on a particular standard of care TKI or chemotherapy +/- immunotherapy (clinical decision that would occur prior to study enrollment)

8. Patients who will be treated with an osteoclast inhibitor must receive dental clearance prior to starting treatment

9. Bone metastases must be detected through radiographic imaging prior to enrollment on this study.

Exclusion Criteria

1. Actionable driver mutation NSCLC patient who has been on anti-bone resorptive therapy

a. Excluded anti-bone resorptive therapy includes: zolendronic acid, pamidronate, alendronate, denosumab or any medication that acts as an osteoclast inhibitor

2. Have any condition or illness that, in the opinion of the investigator, would compromise participant safety or interfere with evaluation while on standard of care treatments for the NSCLC.

3. Patients with actionable driver mutation who received TKI in past or currently on TKI prior to screening

4. Bone metastases that have received prior radiotherapy unless unequivocal progression has occurred since radiation therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer League of Colorado

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erin Schenk, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Hospital

Aurora, Colorado, United States

Site Status: RECRUITING

Lone Tree Medical Center

Lone Tree, Colorado, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Febin Elias

Role: CONTACT

febin.elias@cuanschutz.edu

13037249459

Facility Contacts

Vincent Johnson

Role: primary

vincent.p.johnson@cuanschutz.edu

3037249805

Sung-Ae Woo

Role: primary

sungae.woo@cuanschutz.edu

720-516-9482

Other Identifiers

NCI-2019-03377

Identifier Type: OTHER

Identifier Source: secondary_id

19-0392.cc

Identifier Type: -

Identifier Source: org_study_id