Carcinoma, Non-Small-Cell LungNCT03958565
Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations.
An observational study of Carcinoma, Non-Small-Cell Lung, run by University of Colorado, Denver at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Tyrosine Kinase Inhibitor, Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA] and Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
- Type of treatment
- Injection or infusion
- How many people
- 100 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 Apr 2020to 28 Apr 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: About 30-40% of patients w/ lung cancer develop bone metastases during their disease; the median survival time of patients w/ this secondary lesion is 7 months. In a retrospective study of 259 non-small cell lung cancer (NSCLC) patients, the most common site of skeletal metastases was the spine in 50% of patients, followed by the ribs (27.1%), ilium (10%), sacrum (7.1%), femur (5.7%) \&humerus, scapula \& sternum (2.9%). At our institution, it is standard practice not to use anti-bone resorptive therapy in driver mutation-addicted NSCLC w/ bony metastasis, while anti-bone resorptive therapies are commonly used in NSCLC w/ bony metastases w/o any actionable driver mutation. This study relates to exploring the potential differential need for anti-resorptive bone medications (bisphosphonates or RANK-L inhibitors) in patients w/ advanced non-small cell lung cancer \& bone metastases w/ \& w/o actionable driver mutations.
Who may be able to join
- Provision to sign and date the consent form
- Stated willingness to comply with all study procedures and be available for the duration of the study
- Be a male or female aged 18-100 years
- Pathologically confirmed non-small cell lung cancer
- Molecular testing through a CLIA-validated NGS assay. This can be done using either tissue based samples or blood-based samples (ctDNA)
- ECOG PS 0-2
Show all 9Show fewer
- Decision to be on a particular standard of care TKI or chemotherapy +/- immunotherapy (clinical decision that would occur prior to study enrollment)
- Patients who will be treated with an osteoclast inhibitor must receive dental clearance prior to starting treatment
- Bone metastases must be detected through radiographic imaging prior to enrollment on this study.
Who cannot join
- Actionable driver mutation NSCLC patient who has been on anti-bone resorptive therapy
- Excluded anti-bone resorptive therapy includes: zolendronic acid, pamidronate, alendronate, denosumab or any medication that acts as an osteoclast inhibitor
- 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.
- Patients with actionable driver mutation who received TKI in past or currently on TKI prior to screening
- Bone metastases that have received prior radiotherapy unless unequivocal progression has occurred since radiation therapy
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Colorado Hospital
Aurora, Colorado, 80045
Vincent Johnson, 3037249805, vincent.p.johnson@cuanschutz.edu
Erin Schenk, MD
- Recruiting
Lone Tree Medical Center
Lone Tree, Colorado, 80124
Sung-Ae Woo, 720-516-9482, sungae.woo@cuanschutz.edu
Hannah Robinson, MD
About this study
Official title: Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations
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.
Read the 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
- Being tested
- Tyrosine Kinase Inhibitor, Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA], Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tyrosine Kinase InhibitorBiological
Targeted therapy given as standard of care.
Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]Drug
Given Q4 weeks as standard of care
Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]Drug
Given Q12 weeks for bone disease as standard of care
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Tyrosine Kinase Inhibitor | |
| 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. Receives: Drug: Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]; Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage reduction of urine NTX and serum CTX
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).
Measured: 3 months post-treatment
Secondary outcomes (5)
Skeletal-related events (SREs)
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.
Measured: 1, 3, 6, and 12 months post-treatment
Progression Free Survival (PFS)
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.
Measured: at 1 year
Objective Response Rate (ORR)
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.
Measured: at 1 year
Percentage reduction in the bone turnover markers including urine N-telopeptide (NTX) and serum C-terminal telopeptide (CTX)
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.
Measured: From Baseline at 1, 6, and 12 months post-treatment
Percentage normalization of blood total alkaline phosphatase
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.
Measured: From baseline at 1, 3, 6, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2019
- Study start28 Apr 2020
- Primary completion5 Mar 2028 (estimated)
- Study completion28 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer League of Colorado
- Responsible party
- Sponsor
- Investigators
- Erin Schenk, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03958565
- Sponsor's protocol ID
- 19-0392.cc
- Other IDs
- NCI-2019-03377
- Status last verified
- Jun 2026
- First submitted
- 14 May 2019
- Last updated
- 3 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical laboratory data will be entered into REDCap; the data system includes password protection and internal quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source documents.Data will be tracked using REDCap. Data collected for this study will be analyzed and stored at the University of Colorado Cancer Center. When the study is completed, access to study data will be provided through the UCCC Oncology Clinical Research Support Team.
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations
- ClinicalTrials.gov ID
- NCT03958565
- Acronym / sponsor ID
- 19-0392.cc
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Cancer League of Colorado
- Study start
- 28 Apr 2020 (actual)
- Primary completion
- 5 Mar 2028 (estimated)
- Study completion
- 28 Apr 2028 (estimated)
- First posted
- 22 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Actionable driver oncogene | – | Biological: Tyrosine Kinase InhibitorOne 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. |
| No Actionable Mutations | – | Drug: Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA], Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- About 30-40% of patients w/ lung cancer develop bone metastases during their disease; the median survival time of patients w/ this secondary lesion is 7 months. In a retrospective study of 259 non-small cell lung cancer (NSCLC) patients, the most common site of skeletal metastases was the spine in 50% of patients, followed by the ribs (27.1%), ilium (10%), sacrum (7.1%), femur (5.7%) \&humerus, scapula \& sternum (2.9%). At our institution, it is standard practice not to use anti-bone resorptive therapy in driver mutation-addicted NSCLC w/ bony metastasis, while anti-bone resorptive therapies are commonly used in NSCLC w/ bony metastases w/o any actionable driver mutation. This study relates to exploring the potential differential need for anti-resorptive bone medications (bisphosphonates or RANK-L inhibitors) in patients w/ advanced non-small cell lung cancer \& bone metastases w/ \& w/o actionable driver mutations.
Key inclusion criteria (9 listed)
- Provision to sign and date the consent form
- Stated willingness to comply with all study procedures and be available for the duration of the study
- Be a male or female aged 18-100 years
- Pathologically confirmed non-small cell lung cancer
- Molecular testing through a CLIA-validated NGS assay. This can be done using either tissue based samples or blood-based samples (ctDNA)
Key exclusion criteria (5 listed)
- Actionable driver mutation NSCLC patient who has been on anti-bone resorptive therapy
- 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.
- Patients with actionable driver mutation who received TKI in past or currently on TKI prior to screening
- Bone metastases that have received prior radiotherapy unless unequivocal progression has occurred since radiation therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tyrosine Kinase InhibitorTargeted therapy given as standard of care. | Biological | Actionable driver oncogene |
| Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]Given Q4 weeks as standard of care | Drug | No Actionable Mutations |
| Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]Given Q12 weeks for bone disease as standard of care | Drug | No Actionable Mutations |
Primary outcome
Percentage reduction of urine NTX and serum CTX
Time frame: 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).
5 secondary outcomes
Skeletal-related events (SREs)
Time frame: 1, 3, 6, and 12 months post-treatment
Progression Free Survival (PFS)
Time frame: at 1 year
Objective Response Rate (ORR)
Time frame: at 1 year
Percentage reduction in the bone turnover markers including urine N-telopeptide (NTX) and serum C-terminal telopeptide (CTX)
Time frame: From Baseline at 1, 6, and 12 months post-treatment
Percentage normalization of blood total alkaline phosphatase
Time frame: From baseline at 1, 3, 6, and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2026.
- Individual participant dataSharing planned: Yes. Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical laboratory data will be entered into REDCap; the data system includes password protection and internal quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source documents.Data will be tracked using REDCap. Data collected for this study will be analyzed and stored at the University of Colorado Cancer Center. When the study is completed, access to study data will be provided through the UCCC Oncology Clinical Research Support Team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Erin Schenk, MD principal investigator
University of Colorado, Denver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Carcinoma, Non-Small-Cell Lung, run by University of Colorado, Denver at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Febin Elias (13037249459, febin.elias@cuanschutz.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage reduction of urine NTX and serum CTX (time frame: 3 months post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.