Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy and Safety Study of BIBW 2992 to Treat Lung Cancer Patients (TIMELY)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by University College, London
Boehringer Ingelheim
Information provided by (Responsible Party):
University College, London Identifier:
First received: August 10, 2011
Last updated: April 3, 2013
Last verified: April 2013

August 10, 2011
April 3, 2013
December 2012
December 2014   (final data collection date for primary outcome measure)
Progression free survival [ Time Frame: At 6 months ] [ Designated as safety issue: Yes ]
Progression free survival will be determined by measurement of tumour size using RECIST version 1.1 at progression or date of patient death.
Same as current
Complete list of historical versions of study NCT01415011 on Archive Site
  • Overall response [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: This will be measured in days, from the first day of treatment to the day of death. ] [ Designated as safety issue: Yes ]
  • Change in performance status [ Time Frame: At 1 month ] [ Designated as safety issue: Yes ]
  • Safety [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    For each type of adverse event, the maximum toxicity grade will be obtained for each patient using CTCAE version 4.0 to closely monitor tolerability to BIBW 2992. Focus will be on those with a grade 3 or 4 BIBW 2992 related toxicities. The proportion of patients with any grade 3 or 4 event will also be examined.
  • Progression free survival in patients aged 70 and over [ Time Frame: At progression or patient death ] [ Designated as safety issue: Yes ]
  • Treatment compliance [ Time Frame: Compliance will be examined based on the time between starting treatment and stopping it completely ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
Efficacy and Safety Study of BIBW 2992 to Treat Lung Cancer Patients
Phase II Trial of BIBW 2992 in Suspected Mutant EGFR Lung Cancer Patients Unfit for Chemotherapy

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

Lung cancer is most common cause of death from cancer, of which non-small cell lung cancer (NSCLC) accounts for ~80% of all cases with most patients presenting with advanced disease. Patients medically unfit to receive radical or platinum-doublet palliative systemic therapy, because of poor performance status or comorbidity, account for at least 45% of newly diagnosed cases and have poor survival. Many oncologists have interpreted single-agent chemotherapy data as not clinically meaningful when balanced against toxicities, non-significant improvements in quality of life and comorbidity. Hence, in the UK, this group of patients are predominantly treated by best-supportive care (BSC).

This study aims to examine the efficacy and safety of using an irreversible EGFR inhibitor drug BIBW 2992 to treat patients with non-small cell lung cancer and suspected Epidermal Growth Factor Receptor (EGFR) mutation who are considered unfit for chemotherapy. This drug is currently unlicensed.

There has been only one small prospective study of medically unfit patients with EGFR mutation, but it demonstrated good efficacy with a TKI17. This phase II study of East Asian patients (n=30) with performance status 2-4 and treated with gefitinib demonstrated a rapid improvement in performance status at 1 month, an overall response rate of 66% and median survival of 17.8 months. Whilst gefitinib is licensed for EGFR mutant NSCLC, no prospective studies have yet been performed on medically unfit patients from Western countries. Despite dramatic initial responses, EGFR mutant NSCLC patients treated with gefitinib/erlotinib ultimately relapse. In ~50% of cases this is due to the gefitinib/erlotinib-resistant T790M genotype acquired through either secondary somatic mutation or clonal expansion. There is therefore a need to improve the outcomes of medically unfit patients with suspected EGFR mutation, who would otherwise be treated with best supportive care, and in proven EGFR mutation cases by using an effective EGFR-directed therapy that inhibits EGFRT790M.

Prospective data on medically unfit Western NSCLC patients with EGFR mutation are required to assess the efficacy of EGFR-TKIs. Additionally, given that 50% of such patients will become TKI-resistant through EGFRT790M, new therapies are required to overcome this resistance mechanism.

We aim to recruit patients with clinical characteristics likely to harbour EGFR mutation but with EGFR genotype unknown either due to no tissue suitable for genotyping, failed genotype; these will be patients with adenocarcinoma who are never- or ex-light smokers.

Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Non-Small-Cell Lung
Drug: BIBW 2992
All patients will be given daily oral BIBW 2992 (40mg) administered every 28 days until disease progression/toxicity/clinician decision to stop.
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2015
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Any stage not suitable for radical treatment
  • No tissue suitable for EGFR genotyping, failed genotype, or EGFR genotyping unavailable
  • NSCLC Adenocarcinoma sub-type (including any WHO variant)
  • Eligible smoking history:Never smoker (<100 cigarettes in lifetime), or former smoker (stopped >1year ago and ≤10 pack-years)
  • WHO PS 0-3 and predicted life expectancy > 8 weeks
  • 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 as calculated according to Cockcroft- - Gault formula.
  • 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

Exclusion Criteria:

  • Previous treatment with 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.
  • Symptomatic left ventricular failure with NYHA classification of 3 or more.
  • Active viral hepatitis and/or known HIV positive
  • Known or suspected active drug or alcohol abuse
  • Use of any investigational drug within 8 weeks of registration.
  • Known allergy to BIBW 2992 or other ingredients.
  • Patients on steroids must have been on the same dose for at least 4 weeks.
  • Inability to understand or to comply with the requirements of the trial, trial protocol or to provide informed consent.
  • Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial.
  • Women who are pregnant or breast feeding.
  • Requirement for treatment with any of the prohibited concomitant medications listed in protocol.
18 Years and older
Contact: Laura Hughes 0207 679 9284
United Kingdom
UCL/09/0426, 2011-003608-19
Not Provided
University College, London
University College, London
Boehringer Ingelheim
Principal Investigator: Sanjay Popat, BSc MBBS MRCP PhD Royal Marsden Hospital London
University College, London
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP