NCT05298176

Combining Afatinib and Concurrent Chemotherapy, Followed by Osimertinib and Concurrent Chemotherapy, in Untreated EGFR Positive NSCLC Tumors

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Amsterdam UMC, location VUmc · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim of the COMBINATION trial is to prospectively study the sequential approach of using afatinib combined with a short course of chemotherapy, followed by osimertinib, upon progression and acquisition of a T790M mutation, also combined with a short course of chemotherapy.

Detailed description

The investigators hypothesized that treating advanced stage EGFR mutation positive NSCLC in first line with afatinib and osimertinib in second line (in T790M positive tumors) will cause an apoptotic cell death in a large part of TKI-sensitive cancer cells, resulting in a large reduction of the tumor bulk. Adding cytotoxic chemotherapy after 6 weeks of EGFR-TKI will destroy remaining TKI-resistant subclones at an early stage, when the TKI-resistance tumor volume is the smallest and most vulnerable. The investigators will administer only 2 cycles of chemotherapy to limit toxicity, while maintaining a substantial anti-cancer effect. After progression on afatinib-chemotherapy combination, some participants will develop T790M and will be able treated by osimertinib-chemotherapy combination. So, this strategy will allow the investigators to timely sequence the most appropriate drugs (afatinib and osimertinib with chemotherapy) to get the highest anti-cancer efficiency. In this way, the investigators will avoid long periods of maintenance treatments with chemotherapy or anti-VEGFR treatments that are associated with toxicity, costs, and necessitate the participants to come into the ward for intravenous medication. The limited cycles of chemotherapy also allows the treating physician to again treat the participant with the same chemotherapy regimen once progression occurs after all sensible targeted therapy options have been used. Therefore, the investigators hypothesize that this sequential combination strategy will be more effective than other available strategies and will improve the quality of patient care as compared to current general practice.

Conditions

• Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Afatinib, Osimertinib, Carboplatin and Pemetrexed	This study consists of 2 parts. Part 1 is defined as a first line treatment with afatinib orally (30 mg once a day) for the first 6 weeks, followed by concurrent use of afatinib (20mg once a day, part 1B) plus 2 cycles of carboplatin and pemetrexed (21 days per cycle); followed by afatinib monotherapy (30mg once a day). Part 2 comprises a 2nd line treatment with osimertinib (80 mg once daily) after failure of part 1, only in T790M positive patients for the first 6 weeks, followed by concurrent use of osimertinib (80mg once a day) plus 2 cycles of carboplatin and pemetrexed (21 days per cycle); followed by osimertinib monotherapy (80mg once a day).

Timeline

• Start date: 2022-01-04
• Primary completion: 2024-04-01
• Completion: 2024-04-01
• First posted: 2022-03-28
• Last updated: 2025-03-28

Locations

1 site across 1 country: Netherlands