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

University of Colorado Denver (CU Denver)

Status: Enrolling

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]; Biological: Tyrosine Kinase Inhibitor; Drug: Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]

Study type: Observational

Funder types: Other

Identifiers

NCT03958565

NCI-2019-03377 (Other Identifier)

19-0392.cc

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

100 participants in 2 patient groups

Actionable driver oncogene

Description:

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.

Treatment:

Biological: Tyrosine Kinase Inhibitor

No Actionable Mutations

Description:

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.

Treatment:

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

Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]