E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
stage IIIB/IV or recurrent non small cell lung cancer after failure of first
line chemotherapy |
|
E.1.1.1 | Medical condition in easily understood language |
Special type of cancer of the lung |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non-small cell lung cancer |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
evaluate whether BIBF 1120 in combination with standard therapy of docetaxel in patients with stage IIIB/IV or recurrent NSCLC is more effective as compared to placebo in combination with standard therapy of docetaxel.
primary endpoint: progression free survival |
|
E.2.2 | Secondary objectives of the trial |
overall survival (key secondary endpoint)
tumour response according to the modified RECIST criteria (objective tumour response, disease control, duration of disease control)
incidence and intensity of adverse events according to the common terminology criteria for adverse events (CTCAE version 3.0)
clinical improvement
changes in safety laboratory parameters
quality of life measured by standardized questionnaires (EQ-5D, EORTC QLQ-C-30,
EORTC QLQ-LC-13)
pharmacokinetics of BIBF 1120 (and of clinical relevant metabolites, if feasible) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• male or female patient aged 18 years or older
• histologically or cytologically confirmed, locally advanced and/or metastatic NSCLC of stage IIIB or IV (according to American Joint Committee on Cancers) or recurrent
NSCLC (all histologies)
• relapse or failure of one first line prior chemotherapy (in the case of recurrent disease one additional prior regimen is allowed for adjuvant, neoadjuvant or neoadjuvant plus adjuvant therapy)
• at least one target tumour lesion that has not been irradiated within the past three months and that can accurately be measured by magnetic resonance imaging (MRI) or computed tomography (CT) in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT
• life expectancy of at least three months
• ECOG score of 0 or 1
• patient has given written informed consent which must be consistent with international conference on harmonisation – good clinical practice (ICH-GCP) and local legislation |
|
E.4 | Principal exclusion criteria |
more than one prior chemotherapy regimen for advanced and/or metastatic disease or recurrent NSCLC
more than one chemotherapy treatment regimen prior to first line chemotherapy of advanced and/or metastatic or recurrent NSCLC
previous therapy with other VEGFR inhibitors (other than bevacizumab) or docetaxel for treatment of NSCLC
persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy
treatment with other investigational or anti-cancer drugs or treatment in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial
radiotherapy (except extremities and brain) within the past three months prior to baseline imaging
active brain metastases
radiographic evidence of cavitary or necrotic tumours
centrally located tumours with radiographic evidence (CT or MRI) of local invasion of major blood vessels
history of clinically significant haemoptysis within the past 3 months, therapeutic anticoagulation (except low dose heparin) or antiplatelet therapy, history of major thrombotic or clinically relevant major bleeding event in the past 6 months, known inherited predisposition to bleeding or thrombosis
significant cardiovascular disease
inadequate safety laboratory parameters
significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the present trial
current peripheral neuropathy ≥ CTCAE grade 2 except due to trauma
preexisting ascites and/or clinically significant pleural effusion
major injuries and/or surgery within the past ten days prior to randomisation with incomplete wound healing
serious illness, active infections requiring systemic antimicrobial therapy or concomitant non-oncological disease
patients unwilling to use a medically acceptable contraception
pregnancy or breast feeding
psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol
patients unable to comply with the protocol
active alcohol or drug abuse
other malignancy within the past three years other than basal cell skin cancer, or carcinoma in situ of the cervix
any contraindications for therapy with docetaxel
history of hypersensitivity to docetaxel, polysorbate 80 (Tween 80), BIBF 1120, contrast media |
|
E.5 End points |
E.5.1 | Primary end point(s) |
progression free survival |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
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) | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 119 |
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 | No |
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 |
Austria |
Belarus |
Belgium |
Bulgaria |
China |
Croatia |
Czech Republic |
Denmark |
France |
Georgia |
Germany |
Greece |
India |
Israel |
Italy |
Korea, Republic of |
Lithuania |
Poland |
Portugal |
Romania |
Russian Federation |
Slovakia |
South Africa |
Spain |
Switzerland |
Ukraine |
United Kingdom |
|
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
|
The clinical trial will be considered completed as soon as the last patient is transferred to another program or has completed the first follow-up visit which should take place at least 28 days after end of active treatment (EOT).
Only the patients that remain on this trial will be monitored continuously for their safety and then be reported in a revision to the study report. When protocol specified PFS and OS analyses are complete, no further accumulated analyses are needed. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |