Clinical Trials /

Deciphering Afatinib Response and Resistance With INtratumour Heterogeneity

NCT02183883

Description:

To assess if targeting activating EGFR and HER2 mutations in Non-Small Cell Lung Cancer (NSCLC) is more effective when these mutations are truncal dominant mutations (≥50%), as opposed to non-dominant (≥5 to <50%) or low frequency mutations (<5%). This trial will only be available to patients registered to the TRACERx study (NCT01888601).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Deciphering <span class="go-doc-concept go-doc-intervention">Afatinib</span> Response and Resistance With INtratumour Heterogeneity

Title

  • Brief Title: Deciphering Afatinib Response and Resistance With INtratumour Heterogeneity
  • Official Title: Deciphering Afatinib Response and Resistance With INtratumour Heterogeneity
  • Clinical Trial IDs

    NCT ID: NCT02183883

    ORG ID: UCL/14/0131

    Trial Conditions

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Afatinib Giotrif Afatinib

    Trial Purpose

    To assess if targeting activating EGFR and HER2 mutations in Non-Small Cell Lung Cancer
    (NSCLC) is more effective when these mutations are truncal dominant mutations (50%), as
    opposed to non-dominant (5 to <50%) or low frequency mutations (<5%).

    This trial will only be available to patients registered to the TRACERx study (NCT01888601).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Afatinib Experimental Afatinib, tablet, 40mg, 30mg, 20mg, OD, taken until progression, unacceptable toxicity, intercurrent illness, patient/clinician decision Afatinib

    Eligibility Criteria

    Inclusion Criteria:

    This therapeutic trial is only relevant for patients involved in the TRACERx observational
    study.

    - Subjects must be willing to have a biopsy of relapsed disease. Consent will be
    obtained through the TRACERx study. Procurement of the biopsy sample is not necessary
    at the time of trial registration. However, patients must undergo a biopsy prior to
    commencement of afatinib.

    - Patients must have tumours harbouring a sensitising EGFR mutation or HER2 mutation in
    at least one biopsy at recurrence, or region of the primary sample.

    - Written Informed consent for DARWIN1.

    - No previous exposure to an EGFR TKI.

    - No previous chemotherapy or biological therapy in the advanced setting.

    - Measurable disease by RECIST v1.1.

    - At least 18 years of age.

    - Anticipated life expectancy of at least three months.

    - Adequate organ function as defined by the following baseline values:

    - Absolute neutrophil count (ANC) 1.5x109/L

    - Platelets 100x109/L

    - Serum bilirubin 1.5 x upper limit of normal (ULN). In patients with known
    Gilbert's syndrome, total bilirubin 3xULN with direct bilirubin 1.5xULN

    - Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) 3xULN or 5x
    ULN if liver metastases are present)

    - Creatinine clearance must be 30mL/min

    - Women with child-bearing potential, or men who are able to father a child, must be
    willing to practice acceptable methods of birth control during the trial and for 1
    month after the end of treatment.

    - Women of childbearing potential must have a negative pregnancy test within 14 days
    before the first dose of trial medication.

    Exclusion Criteria:

    - Suitable for radical radiotherapy.

    - Palliative radiotherapy within 2 weeks prior to registration.

    - Palliative radiotherapy to a solitary target lesion.

    - Requirement for intravenous feeding, active peptic ulcer, prior surgical procedures
    affecting absorption or any medical comorbidity affecting gastrointestinal
    absorption.

    - Patients with current or pre-existing interstitial lung disease.

    - Significant or recent acute gastrointestinal abnormalities with diarrhoea as a major
    symptom e.g. Crohn's disease, malabsorption, or CTCAE v4.03 Grade 3 diarrhoea of any
    etiology at baseline.

    - Known hypersensitivity to afatinib or to any of the excipients.

    - Patients with rare hereditary conditions of galactose intolerance, the Lapp lactase
    deficiency or glucose-galactose malabsorption

    - Anti-cancer therapy including chemotherapy, radiation therapy, immunotherapy,
    biologic therapy, or major surgery within 14 days prior to start of trial therapy.

    - Known human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus
    (HCV) infection or syphilis. Subjects with evidence of hepatitis B virus clearance
    may be enrolled.

    - History of other malignancy; Exception: (a) Subjects who have been successfully
    treated and are disease-free for 3 years, (b) a history of completely resected
    non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in
    stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal
    therapy with histologically confirmed tumor lesions that can be clearly
    differentiated from lung cancer target and non-target lesions are eligible.

    - Patients with symptomatic brain metastases.

    - The following cardiac abnormalities:

    - Corrected QT (QTc) interval 480 msecs

    - History of acute coronary syndromes (including unstable angina) within the past
    24 weeks

    - Coronary angioplasty, or stenting within the past 24 weeks

    - Class III, or IV heart failure as defined by the New York Heart Association
    (NYHA) functional classification system

    - History of known arrhythmias (except sinus arrhythmia) within the past 24 weeks

    - Myocardial infarction within the last 6 months

    - Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension etc),
    psychological, familial, sociological, or geographical conditions that do not permit
    compliance with the protocol; or unwillingness or inability to comply with the
    requirements of the trial, trial protocol or to provide informed consent.

    - Pregnant, lactating or actively breastfeeding females.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival (PFS)

    Secondary Outcome Measures

    Overall survival

    Time-to-progression

    Tumour Response

    Toxicity

    Trial Keywords

    Non-small cell lung cancer

    NSCLC

    Afatinib

    Intra-tumour heterogeneity

    Clonal dominance

    Drug resistance

    EGFR

    HER2

    Phase 2