Non-small Cell Lung Cancer Clinical Trial
— DARWIN1Official title:
Deciphering Afatinib Response and Resistance With INtratumour Heterogeneity
Verified date | November 2023 |
Source | University College, London |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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 be available to patients registered to the TRACERx study (NCT01888601), or non-TRACERx patients who have two archival tissue/DNA samples who are willing to have a biopsy of their relapsed disease.
Status | Completed |
Enrollment | 12 |
Est. completion date | March 22, 2023 |
Est. primary completion date | March 22, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 Criteria: - 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. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Aberdeen Royal Infirmary (NHS Grampian) | Aberdeen | |
United Kingdom | Heart of England NHS Foundation Trust | Birmingham | |
United Kingdom | Beatson West of Scotland Cancer Centre (NHS Greater Glasgow & Clyde) | Glasgow | |
United Kingdom | Cr Uk & Ucl Ctc | London | |
United Kingdom | University College London Hospitals NHS Foundation Trust | London | |
United Kingdom | Barnet and Chase Farm Hospitals (Royal Free London NHS Foundation Trust) | London Borough Of Barnet | |
United Kingdom | The Christie NHS Foundation Trust | Manchester |
Lead Sponsor | Collaborator |
---|---|
University College, London | Boehringer Ingelheim |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Progression Free Survival (PFS) | 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. | Up to 60 months | |
Secondary | Overall survival | From date of registration until the date of death from any cause assessed up to 60 months. | Up to 60 months | |
Secondary | Time-to-progression | From date of registration until the date of the last documented progression assessed up to 60 month. | Up to 60 months | |
Secondary | Tumour Response | From date of registration until the date of the last documented response assessed up to 60 months. | Up to 60 months | |
Secondary | Toxicity/Adverse events | Adverse events, including any dose reductions, interruptions and modifications from date of registration up until 60 months. | Up to 60 months |
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