Nintedanib Plus EGFR TKI In EGFR-mutated Non-small Cell Lung Cancer Patients

Trial Title: Nintedanib Plus EGFR TKI In EGFR-mutated Non-small Cell Lung Cancer Patients

NCT ID: NCT06071013

Condition: Non-small Cell Lung Cancer
EGFR Gene Mutation
EGFR-TKI Resistant Mutation

Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Erlotinib Hydrochloride
Gefitinib
Afatinib
Nintedanib

Conditions: Keywords:
nPKC delta
Angiogenesis
EGFR TKI drug resistant

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Nintedanib, gefitinib, erlotinib, afatinib
Description: Nintedanib is a multiple tyrosine kinase inhibitor that can bind competitively to the ATP-binding pocket of these receptors and block intracellular signaling, which is critical for the proliferation and migration. Gefitinib, erlotinib and afatinib are the first- and second- generation of EGFR tyrosine kinase inhibitors that reversibly and irreversibly inhibit the binding of ATP to the phosphate-binding loop of ATP binding site in the kinase domain of EGFR, leading to the inhibition of cell proliferation and induction of apoptosis of cancer cells.
Arm group label: Nintedanib + gefitinib/erlotinib/afatinib

Summary: The purpose of this study is to evaluate the efficacy and safety of Nintedanib with EGFR-TKI in participants with advanced EGFR-TKI-resistant non-small cell lung cancer

Detailed description: The efficacy of the regimen is evaluated by participants' progression-free survival and overall survival. Nintedanib is a medication that blocks endothelial cells in tumor microenvironments and is effective in delaying tumor progression. Nintedanib is also a drug approved for idiopathic pulmonary fibrosis in the clinic. The participants will take 1 nintedanib tablet after a meal twice per day with a twelve-hour interval. EGFR TKI-gefitinib, erlotinib, or afatinib will be taken 1 tablet once per day during each treatment cycle. The treatment cycle in this study is 30 days. In this study, the participants will have a physical exam in 6 weeks and 12 weeks after the initiation of the treatment. In the 6 weeks of the study, the participants will have blood tests and a CT scan. About 5cc of blood will be collected each time. In addition, the participant's tumor will be measured by a CT scan every 12 weeks. If the participants develop any unacceptable symptoms or changes in liver function tests, the participants' treatment may be delayed and/or the dose decreased until the symptoms are disappeared. It may even be necessary to stop your treatment. The doctor will inform the participant of any changes in the participants' treatment schedule or in the doses of medication after he/she evaluates the participants in the clinic. After treatment ends, the participants will have a follow-up visit at the clinic. At this visit, the participants will have a complete physical exam, including blood (about 5cc) tests and CT scan to measure the size of the tumors. This is an investigational study. Up to 20 participants will take part in this study.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Participants between 20 to 70 years old, are pathologically confirmed advanced (stage III and IV) non-small cell lung cancer. 2. Positive EGFR mutations are diagenesis. 3. Participants with histologically/cytologically confirmed locally advanced or metastatic adenocarcinoma subtype NSCLC after the failure of first-line EGFR tyrosine kinase inhibitors- gefitinib, erlotinib, and afatinib. 4. Participants must have adequate hepatic, renal, and bone marrow function Exclusion Criteria: 1. Participants previously received first-line EGFR tyrosine kinase inhibitor with serious side effects. 2. Participants have known hypertension, and chronic liver and gastrointestinal disease. 3. Participants have known brain metastasis. 4. Female participants who are pregnant or breast-feeding 5. Participants have a known diagnosis of EGFR T790M mutation. 6. Participants have a known diagnosis of negative nPKCδ expression by immunohistochemistry (IHC).

Gender: All

Minimum age: 20 Years

Maximum age: 70 Years

Healthy volunteers: No

Start date: September 28, 2023

Completion date: August 27, 2026

Lead sponsor:
Agency: China Medical University Hospital
Agency class: Other

Source: China Medical University Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06071013