Malignant pleural mesothelioma MedDRA version: 21.0 Level: LLT Classification code 10035606 Term: Pleural mesothelioma malignant localised System Organ Class: 100000004864
Conditions
Interventions
Trade Name: VARGATEF
Product Name: Nintedanib 100 mg
Product Code: BIBF 1120
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib
CAS Number: 656247-17-5
Current Sponsor code: BIBF 1120
Sponsors
European Organisation for Research and Treatment of Cancer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ?Histological diagnosis of unresectable Malignant Pleural Mesothelioma (MPM); ? Response or Stable disease according to modified RECIST criteria (Ref. 48) after first line platinum-pemetrexed chemotherapy for 4-6 cycles; ? Last platinum chemotherapy dose administered within 60 days (i.e. randomization must occur within 60 days from the last dose of the last cycle of platinum-pemetrexed chemotherapy); ? Age = 18 years; ? ECOG performance status 0-2; ? Life expectancy of at least 12 weeks in the opinion of the investigator; ? Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose: ? hemoglobin =9.0 g/dL; ? neutrophil count = 1.5 x109/L; ? platelet count = 100 x109/L; ? adequate renal function: ? Serum creatinine = 1.5 mg/dL or = 130 µmol/l; or GFR >45mL/min (If serum creatinine is greater than 1.5 mg/dL, then CrCl must be = 50 mL/min (either according to Cockroft-Gault (Appendix D) or determined by 24 -hour urine collection)); ? No proteinuria CTCAE grade 2 or greater; ? total bilirubin =1.5 x upper limit of normal; ? ALT and AST =1.5 x upper limit of normal for patients without any liver metastasis or =2.5 x upper limit of normal for patients with liver metastasis; ? alkaline phosphatase = 4 x upper limit of normal; ? PT-INR (international normalized ratio of PT) / PTT = 1.5 x upper limit of normal; ? Ability to understand and the willingness to sign a written informed consent; ? Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. ? Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment. ? Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 3 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. ? A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include: ? Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal). Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable). ? Intrauterine device (IUD) ? Intrauterine hormone-releasing system (IUS) ? Bilateral tubal occlusion ? Vasectomised partner ? Sexual abstinence ? Since the effect of nintedanib on the metabolism and efficacy of contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy. Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 3 months after the last study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 97 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: ? Prior systemic anticancer therapy including cytotoxic or immune-checkpoint inhibitor therapy, for MPM, other than first line platinum-based doublet chemotherapy; ? Previous extra-pleural pneumonectomy (other forms of previous surgery eg pleurectomy are acceptable); ? Previous Vascular Endothelial Growth Factor (VEGF) inhibitors (eg bevacizumab, sorafenib, etc); ? Patients that, in the opinion of the investigator, have reduced performance status by 2 ECOG levels (e.g. PS 0 to 2 or PS 1 to 3) from beginning to completion of 1st line chemotherapy; ? Radiotherapy (with the exception of palliative radiotherapy) during study or within 3 weeks of start of study drug; ? Active brain metastases (e.g. stable for 10 %) within the past 6 weeks prior to treatment in the present trial; ? Pre-existing clinically significant ascites and/or clinically significant pleural effusion; ? Active or chronic hepatitis C and/or B infection; ? Active or history of bleeding complications that would prevent anti-angiogenic therapy e.g.: ? Major injuries and/or surgery within the past ten days prior to randomization with incomplete wound healing; no surgery planned during the on-treatment study period; ? Evidence or history of bleeding diathesis or coagulopathy; ? History of clinically significant hemoptysis within the past 3 months (more than one tea-spoon of fresh blood per day); ? History of major thrombotic or clinically relevant major bleeding event in the past 6 months; ? Known inherited predisposition to bleeding or thrombosis; ? Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels; typical mediastinal pleural involvement with mesothelioma remains eligible; ? Clinically active cancer other than mesothelioma within 5 years prior to start of study treatment; ? Radiographic evidence of cavitatory or necrotic tumors; ? Treatment with other investigational drugs or treatment in another clinical interventional trial within the past 4 weeks before start of therapy or concomitantly with the trial; ? Unstoppable use of 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); ? Clinically significant cardiovascular diseases (i.e. hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months, congestive New York Heart Association (NYHA) II, serious cardiac arrhythmia, clinically significant pericardial effusion); ? Any clinical, psychological, familial, sociological or geographical condition that is unstable or could jeopardize the safety of the patient and their compliance in the study protocol and follow-up schedule (those conditions should be discussed with the patient before registration in the trial), e.g.: ? Clinically active ulcers (gastro-intestinal tract, skin); ? Known or suspected allergy to the investigational agent or any agent given in association with this tria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: the primary objective is to evaluate activity in terms of progression-free survival of nintedanib versus placebo as switch maintenance after first line chemotherapy treatment for patients with unresectable Malignant Pleural Mesothelioma ;Secondary Objective: - To evaluate the activity of nintedanib relative to placebo in terms of Overall Survival - To evaluate the activity of nintedanib relative to placebo in terms of Time to Treatment Failure - To evaluate the activity of nintedanib relative to placebo in terms of Overall Response Rate according to modified RECIST - To assess the treatment safety according to CTCAE version 4.0.;Primary end point(s): Progression Free Survival according to modified RECIST criteria;Timepoint(s) of evaluation of this end point: Every 8 weeks (+/-1 week), until disease progression irrespective of treatment delays, interruptions or early treatment discontinuation (for any other reason than disease progression) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall Survival - Time to Treatment Failure - Overall Response Rate (according to modified RECIST) - Safety/toxicity;Timepoint(s) of evaluation of this end point: - Overall Survival: every 4 weeks - Time to Treatment Failure: every 4 weeks - Overall Response Rate (according to modified RECIST): every 8 weeks - Safety/toxicity: every 4 weeks | — |
Countries
Belgium, Egypt, Italy, United Kingdom
Contacts
Public ContactRegulatory Affairs Department
European Organisation for the Research and Treatment of Cancer
Outcome results
None listed