Carcinoma, Non-Small-Cell Lung
Conditions
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.
Interventions
BIOLOGICALTyrosine Kinase Inhibitor
Targeted therapy given as standard of care.
DRUGZoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]
Given Q4 weeks as standard of care
Given Q12 weeks for bone disease as standard of care
Sponsors
University of Colorado, Denver
Cancer League of Colorado
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage reduction of urine NTX and serum CTX | 3 months post-treatment | The percentage reduction in the bone turnover markers including urine N-telopeptide (NTX) and serum C-terminal telopeptide (CTX) from baseline at 3 months from starting TKI (oncogene arm) or anti-resorptive therapy as part of standard systemic therapy (non-oncogene arm). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Skeletal-related events (SREs) | 1, 3, 6, and 12 months post-treatment | Skeletal-related events (SREs) defined as the adverse events associated with bone metastases. SREs would include pathologic fractures, the requirement for surgery or radiotherapy, spinal cord compression. |
| Progression Free Survival (PFS) | at 1 year | Progression Free Survival (PFS) would be defined as progression of disease or death from any cause from time of randomization until the end of study. |
| Objective Response Rate (ORR) | at 1 year | Objective Response Rate (ORR) defined as proportion of patients with reduction in bony metastases as evaluated by using both the MD Anderson (MDA) criteria for patients who receive CT or bone scans and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for patients who undergo FDG PET/CT. These criteria allow for categorization of disease response from complete response to progressive disease. |
| Percentage reduction in the bone turnover markers including urine N-telopeptide (NTX) and serum C-terminal telopeptide (CTX) | From Baseline at 1, 6, and 12 months post-treatment | Percentage reduction in the bone turnover markers including urine N-telopeptide (NTX) and serum C-terminal telopeptide (CTX) from baseline at 1, 6 and 12 months. |
| Percentage normalization of blood total alkaline phosphatase | From baseline at 1, 3, 6, and 12 months | Percentage normalization of blood total alkaline phosphatase from baseline at 1, 3, 6, and 12 months. Normal level of blood total alkaline phosphatase would be defined as equal or less than 147 IU/L. |
Countries
United States
Contacts
CONTACTFebin Elias
PRINCIPAL_INVESTIGATORErin Schenk, MD
University of Colorado, Denver
Outcome results
None listed