| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with confirmed diagnosis of non-small cell lung cancer whose disease progressed after at least one but not more than two lines of cytotoxic chemotherapy of which one must have been a platinum containing regimen with erlotinib or gefitinib for at least 12 weeks. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025054 |
| E.1.2 | Term | Lung cancer non-small cell stage IIIB |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To investigate the efficacy and safety of BIBW 2992 plus best supportive care versus placebo plus best supportive care in a double-blind randomized trial in non-small cell lung cancer patients with progressive disease after at least one but not more than two lines of chemotherapy and at least 12 weeks of treatment with erlotinib or gefitinib. The primary objective of this randomized trial is to determine the efficacy of BIBW 2992 as a single agent as compared to matching placebo in this patient population. Patients on both treatment arms will receive best supportive care in addition to study treatment. Overall survival time will be the primary endpoint defined as the number of days from the date of randomization to the date of death. |
|
| E.2.2 | Secondary objectives of the trial |
1) Progression free survival time
2) Objective response rate
3) Duration of clinical benefit
4) Time to objective response
5) Duration of objective response
6) Safety of BIBW 2992 as indicated by intensity and incidence of adverse events
7) Pharmacokinetics of BIBW 2992
8) Health related quality of life defined as time to deterioration for the three symptoms cough, dyspnea and pain. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Patients with pathological confirmation of non-small cell lung cancer stage III-B (with pleural effusion) adenocarcinoma or stage IV adenocarcinoma who have failed at least one but not more than two lines of cytotoxic chemotherapy (including adjuvant chemotherapy). One of the chemotherapy regimens must have been platinum based.
2) Progressive disease following at least 12 weeks of treatment with erlotinib (Tarceva®) or gefitinib (Iressa®)
3) Eastern Cooperative Oncology Group (ECOG) performance Score 0, 1 or 2.
4) Patients with at least one tumor lesion that can accurately be measured by magnetic resonance imaging (MRI), or computed tomography (CT) in at least one dimension with longest diameter to be recorded as ≥20 mm using conventional techniques or ≥10 mm with spiral CT scan
5) Male and female patients age ≥18 years
6) Life expectancy of at least three (3) months
7) Written informed consent that is consistent with ICH-GCP guidelines |
|
| E.4 | Principal exclusion criteria |
1) More than two prior cytotoxic chemotherapy treatment regimens for relapsed or metastatic non-small cell lung cancer
2) Use of erlotinib or gefitinib within 14 days of treatment Day 1
3) Chemo-, hormone-, (other than megestrol acetate or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks
4) Active brain metastases (stable <4weeks, symptomatic, requiring treatment with anticonvulsants, or leptomeningeal disease). Dexamethasone therapy will be allowed if administered as a stable dose for at least one month before randomization
5) Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption, or CTCAE Grade>2 diarrhea of any etiology at baseline
6) Patients who have any other life threatening illness or organ system dysfunction, which in the opinion of the investigator, would either compromise patient safety or interfere with the evaluation of the safety of the test drug
7) Other malignancies diagnosed within the past five years (other than non-melanomatous skin cancer and in situ cervical cancer)
8) Radiotherapy with the past 2 weeks prior to treatment with the trial drug
9)History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia including New York Heart Association (NYHA) functional classification of 3
10) Cardiac left ventricular function with resting ejection fraction of less than 50% measured by MUGA scan or echocardiogram
11) QTc interval ≥0.47 second
12) Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) ≥400 mg/m2
13) Absolute neutrophil count (ANC) less than 1500 / mm3
14) Platelet count ≤100,000 / mm3
15) Bilirubin ≥1.5 mg / dl (>26 micromol / L, SI unit equivalent)
16) Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≥ three times the upper limit of normal (if related to liver metastases ≥ five times the upper limit of normal)
17) Serum creatinine ≥ 1.5 times of the upper normal limit or calculated/measured creatine clearance ≤45ml/min
18) Women of child-bearing potential or men who are able to father a child unwilling to use a medically acceptable method of contraception during the trial
19) Pregnancy or breast feeding
20) Patients unable to comply with the protocol
21) Patients with any serious active infection including known HIV, active hepatitis B or active hepatitis C
22) Known or suspected active drug or alcohol abuse
23) Patients with known Interstitial Lung Disease (ILD) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
This randomized double blind multi-centre Phase IIb/III trial will be performed in patients with non-small cell lung cancer (NSCLC) who have received previous treatment with at least one but not more than two lines of cytotoxic chemotherapy (one line must have been a platinum containing regimen) and either gefitinib or erlotinib for a period of at least 12 weeks and then progressed.
The primary objective of this randomized trial is to determine the efficacy of BIBW 2992 as a single agent as compared to a matching placebo in this patient population. Patients on both treatment arms will receive best supportive care in addition to study treatment. Overall survival time (OS) will be the primary endpoint defined as the number of days from the date of randomization to the date of death.
Patients enrolled into the trial will be treated and followed until death or lost to follow up. Additional information will be obtained on the safety, and PK profile of BIBW 2992 as well as on the health-related quality of life.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 42 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| All patients should undergo an end of trial evaluation. The termination of trial medication form must be completed for all patients who discontinue or complete the study regardless of the reason. This includes patients who (1) developed adverse events requiring discontinuation of treatment on protocol, (2) were withdrawn for disease progression, (3) dropped out of the trial for other reasons. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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