Clinical trial NCT03958565: Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations.
Official title: Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Cancer League of Colorado
First posted: 2019-05-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

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.

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

Primary outcomes:
measure: Percentage reduction of urine NTX and serum CTX
timeFrame: 3 months post-treatment
Secondary outcomes:
measure: Skeletal-related events (SREs)
timeFrame: 1, 3, 6, and 12 months post-treatment
measure: Progression Free Survival (PFS)
timeFrame: at 1 year
measure: Objective Response Rate (ORR)
timeFrame: at 1 year
measure: Percentage reduction in the bone turnover markers including urine N-telopeptide (NTX) and serum C-terminal telopeptide (CTX)
timeFrame: From Baseline at 1, 6, and 12 months post-treatment
measure: Percentage normalization of blood total alkaline phosphatase
timeFrame: From baseline at 1, 3, 6, and 12 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Lone Tree
country: United States
facility: Lone Tree Medical Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Erin Schenk, MD
role: PRINCIPAL_INVESTIGATOR
References: