A Window of Opportunity Study for Investigating Drug Tolerant Persister (DTP) to Neoadjuvant Osimertinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harbouring EGFR Mutations

NCT04816838 | Unknown

• 1 other identifier: 4-2020-1335
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Osimertinib is a third-generation EGFR (Epidermal growth factor receptor) TKI(Tyrosine kinase inhibitor) for the management of NSCLC(non-small cell lung cancer) harbouring EGFR(Epidermal growth factor receptor) T790M mutation after acquired resistance to previous first-generation EGFR (Epidermal growth factor receptor) TKI(Tyrosine kinase inhibitor) therapy. Moreover, osimertinib was approved or the treatment of patients with EGFR(Epidermal growth factor receptor) mutant NSCLC (non small cell lung cancer) in the first-line setting based on the clinical trial. The clinical activity and favorable toxicity profile of osimertinib has led to broadly research into this drug as a strategy to inhibit and prevent drug resistance in EGFR(Epidermal growth factor receptor) mutant NSCLC (non small cell lung cancer). Evidences of benefit from EGFR (Epidermal growth factor receptor) TKI(Tyrosine kinase inhibitor) in EGFR(Epidermal growth factor receptor) mutant NSCLC (non small cell lung cancer) patients have been increasing in early stages as well as in advance stages. Therefore, adjuvant or neo adjuvant EGFR (Epidermal growth factor receptor) TKI(Tyrosine kinase inhibitor) in operable NSCLC(non small cell lung cancer) patients could improve survival in EGFR(Epidermal growth factor receptor) mutant NSCLC (non small cell lung cancer) patients. Acquired resistance by widespread clinical use has become a hot clinical problem. A variety of target therapies are being developed to overcome tolerance to osimertinib to improve this outcome. This is an approach that should improve the molecular and clinical understanding of the drug resistance. Specifically, we want to investigate innate drug resistance and tumor microenvironment to osimertinib by performing single-cell RNA sequencing (scRNA-seq). and single cell research is obviously needed to develop cancer therapeutic strategies.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rage (ORR)

  after 8 weeks of osimertinib prior to surgery are complete response and partial response determined by RECIST 1.1 criteria

  until 2 years

Secondary Outcomes (7)

• Pathological response rate

  A resected tumor specimen is collected during surgery. (Approximately within 10 weeks after dosing)

• Progression Free Survival (PFS)

  until 2 years

• Overall survival (OS)

  After completion of the clinical treatment, subjects are followed up for 30 days and then observed at 3months intervals for up to 1 year.

• Ratio of inability to resection (operational to non-surgical conversion rate)

  It is performed at study completion, an average of 4year

• Incidence of Adverse Events

  It is performed at study completion, an average of 4year

Study Arms (1)

N/A(Single Arm)

EXPERIMENTAL

Drug: Osimertinib

Interventions

Osimertinib DRUG

\* Osimertinib 80mg once a day(QD) oral(PO) Neoadjuvant Period -If there is no disease progression or unacceptable toxicity, treatment is performed for 2cycles at 1 cycle (28 days) interval Adjuvant Period \- If there is no disease progression of unacceptable toxicity, treatment fis performed for 3years at intervals of 1cycle(28days)

N/A(Single Arm)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and older
• Provision of informed consent prior to any study specific procedures
• Histologically or cytologically confirmed NSCLC(non small cell lung cancer) , performed on a biopsy
• Documented activating EGFR mutation (Exon 19 deletion or L858R)
• Positron emission tomography (PET)-computed tomography (CT) within the last 60 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required)
• Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease
• Documentation that the patient is a candidate for surgical resection of their lung cancer by certified surgeon
• Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
• All toxicity from previous chemotherapy, radiation therapy, or surgical procedures according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 recovered to Grade 1 .
• Patients may receive supplements to meet this requirement this requirement
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
• Bilirubin =\< 1.5 x ULN (Patients with documented Gilbert's syndrome and conjugated bilirubin within the normal range may be allowed into the study; in this event, it will be documented that the patient was eligible based on conjugated bilirubin levels)
• Leukocytes \> 3,000/mcL
• Hemoglobin \>= 9 g/dL, with no blood transfusions in the 28 days prior to study entry

You may not qualify if:

• Leptomeningeal carcinomatosis or other central nervous system (CNS) metastases
• Stage IIIB, or distant metastases (including malignant pleural effusion) identified on PET-CT scan or biopsy
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• History of confirmed, corneal ulceration
• Patients who are known to be serologically positive for human immunodeficiency virus (HIV)
• Active second malignancy, i.e. patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment; patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy for prior malignancy was completed \> 12 months prior and/or bone marrow transplant \> 2 years prior
• Patients who are currently receiving treatment with contraindicated corrected QT interval (QTc) prolonging medications or potent CYP3A4 inducers, if that treatment cannot be either discontinued or switched to a different medication prior to first day of study treatment
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
• Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium \< LLN; Serum/plasma magnesium \< LLN; Serum/plasma calcium \< LLN) congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes
• Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \<1.5 x 109/L;
• Platelet count \<100 x 109/L;
• Haemoglobin \<90 g/L;

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Sun min Lim

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sun min Lim

CONTACT

+82-2227-8296; limlove2008@yuhs.ac

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 25, 2021
• Study Start: May 10, 2021
• Primary Completion: July 1, 2025
• Study Completion: October 1, 2025
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)