Efficacy and Safety Study of Afatinib to Treat Lung Cancer Patients

NCT01415011 | Completed Phase 2 DMC

• 2 other identifiers: UCL/09/04262011-003608-19
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of this study is to examine the efficacy and safety of using afatinib (BIBW 2992) to treat non-small cell lung cancer patients considered unfit for chemotherapy and have either suspected or confirmed Epidermal Growth Factor Receptor (EGFR) mutation.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Afatinib (BIBW2992); EGFR Mutation; Non Small Cell Lung Cancer; Poor performance status; Elderly

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival will be determined by measurement of tumour size using RECIST version 1.1 at progression or date of patient death.

  At 6 months

Secondary Outcomes (6)

• Overall response

  CT scan of chest & abdomen 4 weeks after registartion, then every 8 calender weeks until disease progression. CT scans every 12 weeks if patient is still on BIBW 2992 after 1 year of treatment.

• Overall survival

  This will be measured in days, from the first day of treatment to the day of death.

• Change in performance status

  At 1 month

• Safety

  To be assessed at every timepoint i.e. baseline, fortnightly for the first 2 cycles and then monthly for 12 months and 2 monthly thereafter

• Progression free survival in patients aged 70 and over

  At progression or patient death

Study Arms (1)

Afatinib (BIBW 2992)

EXPERIMENTAL

All patients will be given daily oral afatinib (BIBW 2992) administered every 28 days until disease progression/toxicity/clinician decision to stop. Starting dose is 40mg. 30mg and 20mg will be administered according to protocol dose modification requirements following toxicity.

Drug: Afatinib (BIBW 2992)

Interventions

Afatinib (BIBW 2992) DRUG

All patients will be given daily oral afatinib (BIBW 2992) administered every 28 days until disease progression/toxicity/clinician decision to stop. Starting dose is 40mg. 30mg and 20mg will be administered according to protocol dose modification requirements following toxicity.

Afatinib (BIBW 2992)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any stage not suitable for radical treatment
• Either:
• Confirmed activating EGFR mutation (exons 18-21; e.g. L858R, exon 19 deletions, exon 20 insertions, T790M, list is not exhaustive), and WHO PS 0-3 Or No tissue suitable for EGFR genotyping, failed genotype, or EGFR genotyping unavailable, and NSCLC Adenocarcinoma sub-type, and
• Eligible smoking history:
• Never smoker (\<100 cigarettes in lifetime), or Former smoker (stopped \>1year ago and ≤10 pack-years) and WHO PS 0-2
• Unsuitable for or patient declining chemotherapy due to significant co-morbidity
• Measurable disease according to RECIST version 1.1
• Adequate haematopoietic, hepatic and renal function defined as follows:
• Absolute neutrophil count (ANC) ≤1.5 x 109/L and platelet count ≤100 x 109/L
• Bilirubin ≤1.5 x ULN, ALT (SGPT) ≤3 x ULN (or ≤ 5 x ULN in cases of liver metastases)
• Serum creatinine clearance ≥45 ml/min
• Palliative radiotherapy allowed unless to a solitary target lesion
• Age 18 or over (no upper age limit)
• Written informed consent that is consistent with ICH-GCP guidelines

You may not qualify if:

• Previous treatment with afatinib (BIBW 2992), or any EGFR-directed inhibitor
• Any concurrent anticancer systemic therapy
• Prior chemotherapy for relapsed and/or metastatic NSCLC
• Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and registration
• Suitable for radical radiotherapy
• Palliative radiotherapy within 2 weeks prior to registration
• Palliative radiotherapy to a solitary target lesion
• Surgery (other than biopsy) within 4 weeks prior to registration
• Inability to take oral medication, requirement for intravenous feeding, active peptic ulcer, prior surgical procedures affecting absorption, any medical co- morbidity affecting gastrointestinal absorption
• Patients with current or pre-existing interstitial lung disease
• Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's participation in the trial
• Significant or recent acute gastrointestinal abnormalities with diarrhoea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE version 4.0 Grade ≥3 diarrhoea of any etiology at baseline
• Active brain metastases (defined as stable for \<4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants and/or leptomeningeal disease). Steroids will be allowed if administered as a stable (same) dose for at least one month before trial entry.
• Any other current malignancy or malignancy diagnosed within the past five years (other than non-melanomatous skin cancer and in situ cervical cancer)
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3 or more, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to registration

Sponsors & Collaborators

• University College, London: lead
• Boehringer Ingelheim: collaborator

Study Sites (15)

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

James Paget University Hospital

Great Yarmouth, United Kingdom

Location

East Kent Hospitals

Kent, United Kingdom

Location

Maidstone Hospital

Kent, United Kingdom

Location

St James's University Hospital

Leeds, United Kingdom

Location

Barnet & Chase Farm Hospitals

London, United Kingdom

Location

Charing Cross Hospital

London, United Kingdom

Location

Guy's Hospital

London, United Kingdom

Location

University College Hospital

London, United Kingdom

Location

Musgrove Park Hospital

Somerset, United Kingdom

Location

The Royal Marsden Hospitals

Sutton, United Kingdom

Location

King's Mill Hospital

Sutton in Ashfield, United Kingdom

Location

Weston General Hospital

Weston-super-Mare, United Kingdom

Location

York Hospital

York, United Kingdom

Location

Related Links

• Cancer Research UK \& UCL Cancer Trials Centre

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sanjay Popat, BSc MBBS MRCP PhD

  Royal Marsden Hospital London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2011
• First Posted: August 11, 2011
• Study Start: December 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: November 30, 2018
• Last Updated: January 15, 2019

Record last verified: 2017-10

Locations

GB (15)