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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03727724
Recruitment Status : Active, not recruiting
First Posted : November 1, 2018
Last Update Posted : November 8, 2022
Boehringer Ingelheim
Merck Serono International SA
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Afatinib Drug: Cetuximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Single Arm Study of Afatinib in Combination With Cetuximab in EGFR Exon 20 Insertion Positive Non-small-cell Lung Cancer
Actual Study Start Date : December 4, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

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.

Drug: Afatinib

Drug: Cetuximab

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Duration of response (DOR) [ Time Frame: Scans every 6 weeks until tumor progression ]
    Time from documentation of tumor response to disease progression

  4. 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

  5. Overall survival [ Time Frame: Every 6 weeks up to death ]
    Time form date of start treatment to the date of death from any cause

Other Outcome Measures:
  1. 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727724

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Antoni van Leeuwenhoek
Amsterdam, North-Holland, Netherlands, 1066 CX
VU Medical Center
Amsterdam, Netherlands, 1007 MB
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Maastricht UMC+
Maastricht, Netherlands, 6229 HX
Sponsors and Collaborators
The Netherlands Cancer Institute
Boehringer Ingelheim
Merck Serono International SA
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Principal Investigator: J de Langen, MD, PhD NKI-AvL
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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT03727724    
Other Study ID Numbers: M18ACX
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: November 8, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action