- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03727724
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
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
37
Phase
- 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
-
-
-
Amsterdam, Netherlands, 1007 MB
- VU Medical Center
-
Groningen, Netherlands, 9713 GZ
- University Medical Center Groningen
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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
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 |
Intervention / Treatment |
---|---|
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. |
Injection
Tablet
|
What is the study measuring?
Primary Outcome Measures
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
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
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
Investigators
- 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)
December 4, 2018
Primary Completion (Actual)
September 6, 2022
Study Completion (Actual)
September 6, 2022
Study Registration Dates
First Submitted
September 3, 2018
First Submitted That Met QC Criteria
October 31, 2018
First Posted (Actual)
November 1, 2018
Study Record Updates
Last Update Posted (Actual)
October 18, 2023
Last Update Submitted That Met QC Criteria
October 17, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Cetuximab
- Afatinib
Other Study ID 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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