Advanced (unresectable stage III or IV) BRAF V600 wildtype cutaneous malignant melanoma MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Vargatef
Product Name: Nintedanib 100mg capsules
Product Code: BIBF 1120
Pharmaceutical Form: Capsule, soft
INN or Proposed
Sponsors
University of Essen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed, (surgically incurable or unresectable) stage III or IV, BRAF V600 wildtype metastatic cutaneous malignant melanoma. 2. Written informed consent 3. A minimum of 1 measurable lesion according to RECIST v1.1 criteria. 4. ECOG performance status of 0-1. 5. Adequate hematologic, renal and liver function as defined by laboratory values performed within 14 days prior to initiation of dosing: • Hematologic: o Absolute neutrophil count (ANC) =1.5 x 109/L o Hemoglobin = 9 g/dL (5.6 mmol/L; Subjects may not have had a transfusion within 7 days of screening assessment) o Platelets: = 100 x 109/L • Hepatic o Total bilirubin: = 1.0 x ULN o AST and ALT: = 1.5 x ULN (In the case of liver metastases: 2.5 x ULN) • Renal o Serum creatinine: = 1.5 mg/dL (133 µmol/L) or, if greater than 1.5 mg/dL: Calculated creatinine clearance: = 50 mL/min 6. Women of childbearing potential (WOCBP) should be using an effective method of contraception (Pearl-Index =65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
Exclusion criteria: 1. Prior systemic therapy with taxanes or kinase inhibitors. Any prior therapy for metastatic disease must have been discontinued at least 4 weeks prior to initiation of dosing. 2. Major surgery or radiation therapy within 4 weeks of starting the study treatment (minor surgical procedures such as biopsies are allowed, however patients must have recovered). 3. Known inherited predisposition to bleeding or thrombosis and therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid 2 o Prothrombin time (PT) and partial thromboplastin time (PTT): > 50% of deviation of institutional ULN 4. History of clinically significant haemorrhagic or thromboembolic event in the past 6 months 5. NCI CTCAE (V4.0) grade 3 hemorrhage within 4 weeks of starting the study treatment. 6. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization. 7. Serious, non-healing wound, ulcer, or bone fracture. 8. Known CNS disease. 9. Previous Grade 2 or higher sensory neuropathy. 10. History of or known spinal cord compression, or carcinomatous meningitis, or evidence of active brain metastases (e.g. stable for 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications). 15. Symptomatic peripheral vascular disease. 16. Proteinuria at screening as demonstrated by urine dipstick for proteinuria = 2+ (patients discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate = 1g of protein in 24 hours to be eligible). 17. Known hypersensitivity reaction to any of the components of study treatment (e.g. contrast media) or other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of this study are to characterize the safety and to estimate the efficacy of nintedanib when combined with paclitaxel chemotherapy compared with paclitaxel chemotherapy alone in patients with BRAF wildtype metastatic melanoma not previously treated with taxanes or kinase inhibitors. The primary endpoint of Phase I is the definition of the Maximum Tolerable Dose (MTD) of the nintedanib/paclitaxel combination treatment. The primary endpoint of Phase II is the progression-free survival (PFS) according to RECIST v1.1. ; Secondary Objective: Overall survival • Safety and toxicity (graded according to CTCAE, Version 4.0) • Quality of Life (EORTC QLQ-C30) during therapy (i.e. until end of treatment visit) • Translational research project: identification and evaluation of prognostic and predictive biomarkers by analysis of tumor tissue and serum samples ; Primary end point(s): The primary endpoint of Phase I is the definition of the Maximum Tolerable Dose (MTD) of the nintedanib/paclitaxel combination treatment. The primary endpoint of Phase II is the progression-free survival (PFS) according to RECIST v1.1. ;Timepoint(s) of evaluation of this end point: 12 month after start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival - Safety and toxicity (graded according to CTCAE, Version 4.0) - Quality of Life (EORTC QLQ-C30) during therapy (i.e. until end of treatment visit) - Translational research project: identification and evaluation of prognostic and predictive biomarkers by analysis of tumor tissue and serum samples ;Timepoint(s) of evaluation of this end point: 12 month after start of treatment | — |
Countries
Germany
Contacts
Public ContactDepartment of Dermatology
University of Essen
Outcome results
None listed