EGFR-mutated Lung Cancer in Randomized Investigator-Initiated Study

NCT06486142 | Recruiting Phase 3 DMC

• 1 other identifier: 2021-003755-41
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the optimal sequence of EGFR-inhibitors in lung cancer patients with EGFR-positive tumors not amenable for curative treatment. Life quality, adverse effects and tumor response will be evaluated and analyses of obtained blood and tumor samples will be performed to identify molecular profiles and biomarkers that can be used for treatment decisions.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-small cell lung cancer; EGFR; Osimertinib; Afatinib; Dacomitinib; ctDNA; Resistance mechanisms

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Maximum 6 years

Secondary Outcomes (7)

• Time on TKI-treatment

  Maximum 6 years

• Objective response rate

  Maximum 6 years

• Disease control rate

  Maximum 6 years

• Overall survival

  Maximum 6 years

• Quality of life

  Maximum 6 years

Study Arms (2)

Afatinib/Dacomitinib

ACTIVE COMPARATOR

Drug: Afatinib/Dacomitinib

Osimertinib

ACTIVE COMPARATOR

Drug: Osimertinib

Interventions

Afatinib/Dacomitinib DRUG

Second-generation EGFR-inhibitors

Also known as: Study participants receiving afatinib or dacomitinib until tumor progression/other reasons

Afatinib/Dacomitinib

Osimertinib DRUG

Third-generation EGFR-inhibitor

Also known as: Study participants receiving osimertinib until tumor progression/other reasons

Osimertinib

Eligibility Criteria

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

You may qualify if:

• The subject has given written consent to participate in the study.
• Histological or cytological diagnosis of NSCLC.
• Clinical stage III/IV disease (with or without CNS metastasis) or a recurrence not amenable for curative treatment intention.
• Measurable disease according to RECIST 1.1 criteria or equivalent/modified criteria.
• Any WHO PS.
• Age ≥ 18 years, no upper age limit.
• Treatment-naive with regard to TKI's
• Negative pregnancy test (blood or urine test)
• For fertile participants, adequate contraception should be used; intrauterine device, bilateral tubal occlusion, vasectomy or abstinence (a reduced effect of hormonal contraception methods due to the drugs cannot be excluded). Pregnancy should be avoided during treatment and the first 4 months following treatment discontinuation.

You may not qualify if:

• Condition incompatible with the study or with the planned treatment.
• Present (not radically treated/no planned radical treatment of) other primary malignancy with metastatic potential.
• Co-enrolment in other interventional trial if incompatible with ERIS according to investigator (e.g. due to potential drug interactions).
• Intake of hypericum perforatum (intake must be interrupted before start of study treatment).
• All subjects should avoid concomitant use of medications with known interaction with planned treatment, whenever feasible. If the administration of a medication interacts with any of the three investigational treatments and cannot be exchanged or managed in order to avoid interactions the patient is excluded from the trial.
• Drugs that can either increase or decrease the concentration of osimertinib in plasma:
• Strong activators of CYP3A. Simultaneous administration should be avoided.
• Regular CYP3A4-inhibitors should be used with caution or be avoided.
• Drugs that can either increase or decrease the concentration of afatinib in plasma:
• Strong inhibitors of P-glycoprotein should not be administered simultaneously with afatinib, instead it should preferably be 6-12 hours between.
• Strong activators of P-glycoprotein may reduce exposure of afatinib
• Drugs that can either increase or decrease the concentration of dacomitinib in plasma:
• Proton pump inhibitors should be avoided.
• Simultaneous administration of drugs that are metabolized by CYP2D6 should be avoided. If simultaneous use of that kind of medications are considered necessary, dose recommendations for simultaneous use of respective drug should be followed.
• Any evidence of severe or uncontrolled systemic diseases which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.

Sponsors & Collaborators

• Region Skane: lead
• Swedish Lung Cancer Study Group: collaborator

Study Sites (1)

Skåne university hospital

Lund, Sweden

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib; dacomitinib; osimertinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Maria Planck, MD, PhD

CONTACT

004646171000; maria.planck@med.lu.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: July 3, 2024
• Study Start: September 21, 2022
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

SE (1)