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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат Tyrosine Kinase Inhibitor
  Targeted therapy given as standard of care.
• Препарат Zoledronic Acid 4 MG/100 ML Intravenous Solution [ZOMETA]
  Given Q4 weeks as standard of care
• Препарат Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
  Given Q12 weeks for bone disease as standard of care

Первичные конечные точки

• Percentage reduction of urine NTX and serum CTX [Срок оценки: 3 months post-treatment]

Вторичные конечные точки (5)

• Skeletal-related events (SREs) [Срок оценки: 1, 3, 6, and 12 months post-treatment]
• Progression Free Survival (PFS) [Срок оценки: at 1 year]
• Objective Response Rate (ORR) [Срок оценки: at 1 year]
• Percentage reduction in the bone turnover markers including urine N-telopeptide (NTX) and serum C-terminal telopeptide (CTX) [Срок оценки: From Baseline at 1, 6, and 12 months post-treatment]
• Percentage normalization of blood total alkaline phosphatase [Срок оценки: From baseline at 1, 3, 6, and 12 months]

Критерии участия

Критерии включения

• 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
• 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.

Критерии исключения

• 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

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Другое

Центры проведения

США · 2 центра

• University of Colorado Hospital — Aurora
• Lone Tree Medical Center — Lone Tree

Идентификаторы

NCT: NCT03958565 · 19-0392.cc · NCI-2019-03377

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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