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

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ClinicalTrials.gov Identifier: NCT03958565
Recruitment Status : Recruiting
First Posted : May 22, 2019
Last Update Posted : May 22, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
At our institution it is a standard practice not to use anti-bone resorptive therapy in driver mutation addicted NSCLC with bony metastasis, while anti-bone resorptive therapies are commonly used in NSCLC with bony metastases without 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 with advanced non-small cell lung cancer and bone metastases with and without actionable driver mutations.

Condition or disease Intervention/treatment
Carcinoma, Non-Small-Cell Lung Biological: Tyrosine Kinase Inhibitor Drug: Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA] Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]

Detailed Description:

Primary Objective:

- To assess percentage normalization of urine NTX, 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. All the patients will have an elevated fasting NTX at baseline (prior to treatment).

Secondary Objectives:

  • To assess percentage normalization of urine NTX in patients with NSCLC and bone metastases 1) with actionable driver oncogene on TKI at 1, 6, and 12 months post treatment and 2) without actionable mutations on SOC therapy (chemotherapy/immunotherapy) treated with zoledronic acid or denosumab at the same time periods as for 1.
  • To assess skeletal related events (SREs) on therapy for both arms 1 and 2.
  • To estimate progression free survival (PFS) and overall response rate (ORR), as determined per 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 as SOC.
  • To assess percentage normalization of blood total alkaline phosphatase from baseline at 1, 3, 6, and 12 months post treatment, tested as SOC

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations
Actual Study Start Date : April 15, 2019
Estimated Primary Completion Date : March 5, 2022
Estimated Study Completion Date : March 5, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Tyrosine

Group/Cohort Intervention/treatment
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.
Biological: Tyrosine Kinase Inhibitor
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.
Drug: Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]
Given Q4 weeks as standard of care

Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
Given Q12 weeks for bone disease as standard of care




Primary Outcome Measures :
  1. Percentage normalization of urine NTX [ Time Frame: 3 months post-treatment ]
    The percentage normalization in the bone turnover marker urine N-telopeptide (NTX) from baseline at 3 months from starting TKI (oncogene arm) or anti-resorptive therapy as part of standard systemic therapy (non-oncogene arm).


Secondary Outcome Measures :
  1. Skeletal-related events (SREs) [ Time Frame: 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.

  2. Progression Free Survival (PFS) [ Time Frame: 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.

  3. Objective Response Rate (ORR) [ Time Frame: 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.

  4. Percentage normalization in the bone turnover marker urine N-telopeptide (NTX) [ Time Frame: From Baseline at 1, 6, and 12 months post-treatment ]
    Percentage normalization in the bone turnover marker urine N-telopeptide (NTX) from baseline at 1, 6 and 12 months.

  5. Percentage normalization of blood total alkaline phosphatase [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
About 30-40% of patients with lung cancer develop bone metastases during the course of their disease; the median survival time of patients with 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%) and humerus, scapula and sternum (2.9%). At our institution it is a standard practice not to use anti-bone resorptive therapy in driver mutation addicted NSCLC with bony metastasis, while anti-bone resorptive therapies are commonly used in NSCLC with bony metastases without 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 with advanced non-small cell lung cancer and bone metastases with and without actionable driver mutations.
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 with bone metastasis and elevated urine NTX level (i.e. ≥ 64nmol BCE/mmol creatinine at baseline) with or without driver actionable oncogene
  5. ECOG PS 0-2
  6. Decision to be on a particular standard of care TKI or chemotherapy/immunotherapy (clinical decision that would occur prior to study enrollment)

Exclusion Criteria:

  1. Actionable driver mutation NSCLC patient who has been on anti-bone resorptive therapy
  2. Have any condition or illness that, in the opinion of the investigator, would compromise participant safety or interfere with evaluation of the drug study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03958565


Contacts
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Contact: Paula Fisk 720-848-0671 Paula.fisk@ucdenver.edu
Contact: Joshua Saginaw 720-848-9281 Joshua.saginaw@ucdenver.edu

Locations
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United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Paula Fisk    720-848-0671    Paula.fisk@ucdenver.edu   
Principal Investigator: Ross Camidge, MD         
Sponsors and Collaborators
University of Colorado, Denver
National Cancer Institute (NCI)

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03958565     History of Changes
Other Study ID Numbers: 19-0392.cc
P30CA046934 ( U.S. NIH Grant/Contract )
First Posted: May 22, 2019    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: immediately following publication. no end date.
Access Criteria: Anyone who wishes to access the data. any purpose. Data are available indefinitely.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Zoledronic Acid
Denosumab
Pharmaceutical Solutions
Bone Density Conservation Agents
Physiological Effects of Drugs