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

Title

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

Clinical Trial IDs

  • ORG STUDY ID: UCL/14/0131
  • NCT ID: NCT02183883

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
AfatinibGiotrifAfatinib

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).

Trial Arms

NameTypeDescriptionInterventions
AfatinibExperimentalAfatinib, 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.

          -  ECOG performance status 0-3

          -  No previous exposure to an EGFR TKI (other than afatinib) or HER2 targeted therapy

          -  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) or syphilis infection. 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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Up to 60 months
Safety Issue:
Description:From date of registration until the date of the last documented progression or date of death from any cause, whichever comes first, assessed up to 60 months.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 60 months
Safety Issue:
Description:From date of registration until the date of death from any cause assessed up to 60 months.
Measure:Time-to-progression
Time Frame:Up to 60 months
Safety Issue:
Description:From date of registration until the date of the last documented progression assessed up to 60 month.
Measure:Tumour Response
Time Frame:Up to 60 months
Safety Issue:
Description:From date of registration until the date of the last documented response assessed up to 60 months.
Measure:Toxicity
Time Frame:Up to 60 months
Safety Issue:
Description:Adverse events, including any dose reductions, interruptions and modifications from date of registration up until 60 months.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University College, London

Trial Keywords

  • Non-small cell lung cancer
  • NSCLC
  • Afatinib
  • Intra-tumour heterogeneity
  • Clonal dominance
  • Drug resistance
  • EGFR
  • HER2
  • Phase 2

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