Osimertinib and Etoposide as First-Line Treatment in Osimertinib-Resistant Advanced EGFR-Mutant NSCLC

NCT06436144 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ABC2024521
• Study Type: interventional
• Target: 93
• Locations: 0 countries
• Sites: N/A

Brief Summary

Osimertinib, though a standard first-line treatment for EGFR-mutant advanced NSCLC, shows primary resistance in 10-30% of patients, leading to disease progression within 3-4 months. This resistance is linked to co-mutations in genes like TP53, RB1, and PIK3CA, among others. Studies indicate that Topo II inhibitor Etoposide (VP-16) can reduce cell survival, enhance DNA damage, and delay resistance in Osimertinib-resistant cells, suggesting a potential combination therapy to manage resistance.This study is a single-center, prospective, single-arm study evaluating the efficacy and safety of osimertinib combined with etoposide as a first-line treatment in patients with osimertinib-resistant or -insensitive advanced non-small cell lung cancer (NSCLC). The study focuses on patients with advanced NSCLC (stage IIIB or IV) with EGFR-sensitive mutations who developed slow resistance to osimertinib and for whom secondary biopsy after resistance did not identify any therapeutic targets.

Conditions

Non Small Cell Lung Cancer; EGFR Gene Mutation; Non Small Cell Lung Cancer Stage IIIB; Non-small Cell Lung Cancer Stage IV

Keywords

Non Small Cell Lung Cancer; EGFR Gene Mutation; Primary drug resistance of oxitinib

Outcome Measures

Primary Outcomes (1)

• Objective Remission Rate (ORR) as assessed by RECIST v1.1

  To evaluate the efficacy of osimertinib combined with etoposide as first-line treatment in patients with osimertinib-resistant or -insensitive, advanced EGFR-mutant non-small cell lung cancer. ORR will be defined as the proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.

  Within 1 month after treatment

Secondary Outcomes (4)

• Two-Year Overall Survival Rate

  Up to 2 years after the start of treatment

• One-Year Progression-Free Survival Rate

  Up to 1 year after the start of treatment

• Disease Control Rate (DCR) within One Month

  Within 1 month after treatment

• Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  Within 1 month after treatment

Study Arms (1)

Osimertinib Combined With Etoposide Soft Capsule

EXPERIMENTAL

Drug: Osimertinib

Interventions

Osimertinib DRUG

Etoposide Soft Capsules Dosage：25mg/tablet, 2 tablets/time, taken continuously for 21 days, and stopped for one week. Osimertinib Dosage：80mg/tablet, 1 tablet/time, QD, taken for two cycles.

Also known as: Etoposide Soft Capsules

Osimertinib Combined With Etoposide Soft Capsule

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 79 years.
• Locally advanced (stage IIIB) or metastatic (stage IV) EGFR-mutant NSCLC.
• Harboring an EGFR sensitizing mutation (Exon 19 deletion or L858R).
• Received at least two cycles of first-line osimertinib treatment, with a best response of stable disease or slow progression.
• Life expectancy greater than 3 months.
• At least one measurable tumor lesion meeting the following criteria:
• No prior radiation therapy; 2.Measurable by chest CT or PET-CT, with a longest diameter ≥ 10 mm at baseline (short axis ≥ 15 mm for lymph nodes); 3.Amenable to accurate repeated measurements.

You may not qualify if:

• Currently receiving or planning to receive other anti-cancer therapies.
• Having contraindications to osimertinib or etoposide.
• Harboring known targetable osimertinib resistance mechanisms.

Sponsors & Collaborators

• Daping Hospital and the Research Institute of Surgery of the Third Military Medical University: lead

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

Central Study Contacts

He Yong

CONTACT

86-23-68757791; heyong8998@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 21, 2024
• First Posted: May 30, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 30, 2024

Record last verified: 2024-05