The project aims for screening for potential biomarkers and biomarker combinations relevant for second line setting in NSCLC during combinational therapy with docetaxel and nintedanib. The predicitve value of such profiles should then be evaluated in larger cohorts.
Conditions
Interventions
Trade Name: Vargatef
Product Name: Nintedanib (BIBF 1120)
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib
Other descriptive name: BIBF 1120
Concentration unit: mg milligram(s)
Conce
Sponsors
Medical University Innsbruck
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients of at least 18 years of age 2. Histologically confirmed, adenocarcinoma of the lung, after failure of first line platinum-based chemotherapy. First line chemotherapy for locally advanced, or metastatic (stage IIIB or IV NSCLC according to American Joint Committee on Cancers, Version 7) or recurrent disease may include continuation or switch maintenance therapy administered in the absence of disease progression. One prior adjuvant and/or neoadjuvant chemotherapy is permissible. 3. Time between start of first-line chemotherapy and relapse (defined by RECIST criteria, date of CT) = 9 months (275 days) or = 6 months (183 days). (Commentary: Patients relapsing between 184 – 274 days after start of first-line chemotherapy are not evaluable). 4. At least one target tumor lesion that has not been irradiated within the past three months and that can be accurately measured by computerized tomography (CT) with a longest diameter of = 10 mm or =15 mm in the short-axis diameter for a lymph node. If there is only one target lesion, and it is a non-lymph node, it should have a longest diameter of =15 mm 5. ECOG performance status score (0 or 1) 6. Signed and dated written informed consent in accordance with ICH-GCP guidelines and the local legislation 7. Before study entry a re-biopsy of the tumor is mandatory for inclusion. A CT-guided biopsy or bronchoscopy with 5-6 core biopsies is required to enable the acquisition of adequate tissue. Routine IHC analysis for tumor diagnostics should be performed. EGFR mutational status and EML4/ALK status have to be assessed on the biopsies. 8. Patients will be asked if they voluntarily agree to obtain tumor tissue post mortem. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1) More than one prior line of chemotherapy (i.e. 2nd or 3rd line chemotherapy) for advanced and/or metastatic (stage III B or IV NSCLC) or recurrent disease. Patients known to be positive for activating Epidermal Growth Factor Receptor (EGFR) mutation. Patients known to be positive for ALK translocation. Non-permissible treatments: Previous therapy with other VEGF or VEGFR inhibitors or docetaxel for the treatment of NSCLC at any time. 2) Prior monotherapy with an EGFR inhibitor except as maintenance therapy 3) Non-permissible treatments within 4 weeks prior to start of study therapy: a) Other investigational drugs b) Chemo-, hormone-, radiotherapy (except for radiotherapy to extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors c) Radiotherapy (except extremities and brain) within the past three months prior to baseline imaging d) Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy (AE from previous treatment = Grade 2) e) In case of prior maintenance treatment the last administration should have been performed at least 3 weeks or longer prior to start of study therapy f) Patients receiving erythropoiesis stimulating agents (ESA) 4) Laboratory values outside the following ranges: a) Serum creatinine > 1.5 times the upper limit of normal (ULN) b) Proteinuria CTCAE grade 2 or greater c) Total bilirubin above the upper limit of normal d) ALT or AST > 1.5 x upper limit of normal e) Prothrombin time and/or partial thromboplastin time greater than 50 % deviation from normal limits f) International normalised ratio ( INR) > 3 g) Absolute neutrophil count (ANC) 10 %) within the past 6 weeks prior to treatment in the present trial c) Current peripheral neuropathy, CTCAE grade 2, except due to trauma d) Major injuries and/or surgery within the past ten days prior to randomisation with incomplete wound healing e) Decompensated diabetes mellitus or other contraindication to high dose corticosteroid therapy f) Active or chronic hepatitis C and/or B infection g) Serious illness or concomitant non-oncological disease such as neurologic-, psychiatric active alcohol or drug abuse, infectious disease or active ulcers (gastro-intestinal malabsorption or other conditions, skin), history of hollow-organ perforations 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 h) Other malignancy within the past three years other than basal cell skin cancer, or carcinoma in situ of the cervix i) Leptomeningeal disease or active brain metastases. If brain metastases have been treated, they must be stable for >4 weeks. Dexamethasone therapy will be allowed if administered as stable dose for at least two weeks before randomisation j) Radiographic evidence of cavitary tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels k) History of clinically significant haemoptysis within the past 3 months (more than one teaspoon of fresh blood per day) l) Bleeding or thrombotic disorders requiring anticoagulant therapy such as warfarin, or similar agents requiring therapeutic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of the study is to explore novel biomarkers and to evaluate biomarker combinations measured in different biosamples (plasma, whole blood, DNA, tumor tissue) when combined with clinical parameters.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint of the study will be an exploratory primary endpoint which combines progression free survival (PFS) in conjunction with the planned biomarker analysis. ;Timepoint(s) of evaluation of this end point: Tumor progression has to be performed at six weeks intervals starting six weeks (+/- 2 days) after very first administration of doxetacel. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o Eploratory primary endpoint Progression free survival (PFS) in conjunction with biomarker analysis. o Progression free survival (PFS): This is defined as the interval of time between start of the actual therapy and the first documentation of progression or death. o Time to progression during AAT (aTTP): This modified endpoint is defined as the interval of time between the time of marker analysis and the first documentation of progression or death. ;Timepoint(s) of evaluation of this end point: Progression free survival (PFS) is evaluated in intervals of six weeks together with biomarker analysis. Final analyses will be performed at the end of the study. | — |
Countries
Austria
Contacts
Public ContactDepartment of Internal Medicine V
Medical University Innsbruck
Outcome results
None listed