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 |
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E.1.1.1 | Medical condition in easily understood language |
Special type of cancer of the lung |
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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 | 19.1 |
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 |
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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 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. |
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E.2.2 | Secondary objectives of the trial |
A secondary aim is to obtain safety information as well as information on quality of life of patients treated with BIBF 1120 in combination to standard therapy with docetaxel. In addition, blood will be collected for pharmacokinetic analysis. |
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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 |
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E.4 | Principal exclusion criteria |
• more than one prior chemotherapy regimen for advanced and/or metastatic or recurrent NSCLC
• more than one chemotherapy treatment regimen (either neoadjuvant or adjuvant or neoadjvant plus adjuvant) 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 drugs or treatment in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial
• chemo-, hormone-, radio-(except for extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past four weeks prior to treatment with the trial drug. I.e. the minimum time elapsed since the last anticancer therapy and the first administration of BIBF 1120 must be four weeks
• radiotherapy (except extremities and brain) within the past three months prior to baseline imaging
• active brain metastases (e.g. stable for < 4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomisation) or leptomeningeal disease
• 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 (more than one tea spoon of fresh blood per day)
• therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid ≤ 325mg per day)
• history of major thrombotic or clinically relevant major bleeding event in the past 6 months
• known inherited predisposition to bleeding or thrombosis
• significant cardiovascular diseases (i.e. hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
• serum creatinine > 1.5 times the upper limit of normal
• proteinuria CTCAE grade 2 or greater
• total bilirubin above the upper limit of normal
• ALT and/or AST > 1.5 x upper limit of normal
• prothrombin time and/or partial thromboplastin time greater than 50 % deviation from normal limits
• absolute neutrophil count (ANC) < 1500/microL (= mm3)
• platelets < 100000/ microL (= mm3)
• haemoglobin < 9.0 g/dL
• 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 infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal)
therapy
• decompensated diabetes mellitus or other contraindication to high dose corticosteroid therapy
• gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
• active or chronic hepatitis C and/or B infection
• serious illness or concomitant non-oncological disease such as neurologic-, psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
• patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condomes for participating males) during the trial and for at least twelve months after end of active therapy
• pregnancy or breast feeding
• psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
• 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 severe hypersensitivity reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80)
• hypersensitivity to BIBF 1120 and/or the excipients of the trial drugs
• hypersensitivity to contrast media |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline, every 6 weeks thereafter starting with the very first docetaxel administration, at the end of treatment visit and at the end of study visit (last patient visit according to the clinical trial protocol). For further information, please kindly refer to the clinical trial protocol precedures flowchart. |
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E.5.2 | Secondary end point(s) |
• 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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please kindly refer to the clinical trial protocol precedures flowchart and to section 6.2 (Trial procedures at each visit) of the clincial trial protocol. |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 2 |
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 |
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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 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. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |