Status:
COMPLETED
Deciphering Afatinib Response and Resistance With INtratumour Heterogeneity
Lead Sponsor:
University College, London
Collaborating Sponsors:
Boehringer Ingelheim
Conditions:
Non-small Cell Lung Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
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...
Detailed Description
Increasing evidence suggests that clonal dominance of the drug target should be considered when stratifying therapeutics in solid tumours. It is likely that intratumour heterogeneity and cancer subclo...
Eligibility Criteria
Inclusion
- Subjects must be willing to have a biopsy of relapsed disease. Consent will be obtained through the TRACERx study or with the 'trial entry tissue collection' consent form(non-TRACERx patients). 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.
- Non-TRACERx patients must have at least two archival tissue/DNA samples of their disease available.
- 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. Patients without measurable disease may be eligible following discussion with the CI and UCL CTC but will not count towards the primary PFS endpoint.
- 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 highly effective methods of contraception 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
- Currently suitable for radical radiotherapy.
- 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
- Women of childbearing potential, or men who are able to father a child, unwilling to use a highly effective method of contraception during the trial.
- Anti-cancer therapy including chemotherapy, 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.
Key Trial Info
Start Date :
December 16 2016
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 22 2023
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT02183883
Start Date
December 16 2016
End Date
March 22 2023
Last Update
November 29 2023
Active Locations (7)
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1
Aberdeen Royal Infirmary (NHS Grampian)
Aberdeen, United Kingdom
2
Barnet and Chase Farm Hospitals (Royal Free London NHS Foundation Trust)
Barnet, United Kingdom
3
Heart of England NHS Foundation Trust
Birmingham, United Kingdom
4
Beatson West of Scotland Cancer Centre (NHS Greater Glasgow & Clyde)
Glasgow, United Kingdom