Afatinib and Cetuximab in Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Positive Non-small-cell Lung Cancer (AFACET)

October 17, 2023 updated by: The Netherlands Cancer Institute

Phase II Single Arm Study of Afatinib in Combination With Cetuximab in EGFR Exon 20 Insertion Positive Non-small-cell Lung Cancer

This is a single arm open-label multi-center phase II study, investigating disease control rate after 18 weeks of treatment with afatinib/cetuximab combination therapy in patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR exon 20 insertion.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
37

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1007 MB
        • VU Medical Center
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen
      • Maastricht, Netherlands, 6229 HX
        • Maastricht UMC+
    • North-Holland
      • Amsterdam, North-Holland, Netherlands, 1066 CX
        • Antoni van Leeuwenhoek

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically or cytologically confirmed stage IV non-small cell lung cancer, harboring an EGFR exon 20 insertion mutation.
  • 18 years or older at time of study entry.
  • Life expectancy of at least three months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see Appendix 1).
  • Measurable disease, according to RECIST 1.1.
  • At baseline adequate fresh or archived tissue from a histological biopsy or a cellblock obtained by fine needle aspiration of a tumor lesion that is not radiated prior to biopsy, must be available. Baseline tissue samples must have been obtained after the last line of systemic therapy prior to study entry.
  • Adequate normal organ and marrow function as defined below:
  • Absolute leukocyte count ≥ 3 x 109/L (> 3000 per mm3)
  • Platelet count ≥ 75 x 109/L (>75,000 per mm3)
  • Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ 3 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x upper limit of normal (ULN).
  • Serum creatinine clearance >30 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
  • Women of child-bearing potential: these subjects must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment and agree to use highly effective contraception, as defined in section 5.2.2, from 7 days prior to enrollment, throughout the treatment period and for seven months after completion of the treatment with cetuximab.
  • Males must agree to take appropriate precautions to avoid fathering a child from the first dose of study treatment through 3 months after the final administration of investigational drugs.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Ability to give written informed consent before patient registration.

Exclusion Criteria:

  • Participation in another clinical study with an investigational product during the last 2 weeks.
  • Prior treatment with EGFR targeting antibodies (prior treatment with EGFR TKI's is allowed).
  • Other active malignancy.
  • History of hypersensitivity to afatinib or cetuximab.
  • Major surgery (excluding diagnostic procedures e.g. mediastinoscopy or video assisted thoracic surgery (VATS) biopsy) within 28 days of the start of study treatment.
  • Radiotherapy less than two weeks prior to the start of study treatment.
  • Symptomatic brain metastases.
  • Breast feeding is not allowed during study treatment.
  • Uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, myocardial infarction within 12 months prior to the study entry, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety and anti-tumor activity of the test drugs.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Afatinib plus cetuximab

Afatinib, 40 mg once daily, orally.

Cetuximab, 500 mg/m² intravenously, every 2 weeks.

Treatment will be continued until tumor progression (according RECIST v1.1) confirmed by tumor imaging, unacceptable toxicity, or death occurs.
Drug: Cetuximab
Injection
Drug: Afatinib
Tablet

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Disease control rate after 18 weeks
Time Frame: 18 weeks
To determine the disease control rate at 18 weeks of afatinib and cetuximab treatment in patients with NSCLC harboring an EGFR exon 20 insertion mutation.
18 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective tumor response
Time Frame: Scans every 6 weeks until tumor progression, start of another treatment or death.
Objective tumor response (complete response and partial response)determined by RECIST v1.1.
Scans every 6 weeks until tumor progression, start of another treatment or death.
Safety (intensity and incidence of adverse events)
Time Frame: Up to 30 days after last study drug intake.
Safety as indicated by intensity and incidence of adverse events, graded according to NCI CTCAE Version 4.03.
Up to 30 days after last study drug intake.
Duration of response (DOR)
Time Frame: Scans every 6 weeks until tumor progression
Time from documentation of tumor response to disease progression
Scans every 6 weeks until tumor progression
Progression free survival
Time Frame: Until progression, every 6 weeks up to progression
Time from the date of start treatment to the date of the first documented tumor progression as determined by RECIST1.1, or death due to any cause
Until progression, every 6 weeks up to progression
Overall survival
Time Frame: Every 6 weeks up to death
Time form date of start treatment to the date of death from any cause
Every 6 weeks up to death

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Genetic profiling to assess predictors of response and resistance - circulating free (cf)DNA
Time Frame: At baseline, cycle 1 day 15 and at treatment discontinuation (expected 6 months after start)
cfDNA samples will be collected to assess predictors of response and resistance.
At baseline, cycle 1 day 15 and at treatment discontinuation (expected 6 months after start)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Netherlands Cancer Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Boehringer Ingelheim
Merck Serono International SA

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: J de Langen, MD, PhD, NKI-AVL

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 4, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 6, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 6, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 3, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 1, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 18, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • M18ACX

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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