Determine the safety, tolerability and maximum tolerated dose of anetumab ravtansine (BAY 94-9343) in combination with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 in subjects with mesothelin-expressing predominantly epithelial mesothelioma or nonsquamous non-small-cell lung cancer.
|First Received Date||November 30, 2015|
|Last Changed Date||July 13, 2018|
|Start Date||February 3, 2016|
|Anticipated Primary Completion Date||July 18, 2018|
|Primary Outcome Measures||
Maximum tolerated dose (MTD) [Time Frame: Up to 2 years]
Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability [Time Frame: Up to 2 years]
|Secondary Outcome Measures||
Plasma concentrations of anetumab ravtansine (BAY 94-9343), pemetrexed and cisplatin [Time Frame: - BAY 94-9343: C1D1,D2,D3,D8,D15, C2D1, C3D1,D2,D3,D8,D15, C4D1, C6D1 and subsequent cycles every 3rd cycle up to 2 years or until discontinuation of study treatment, whichever comes first - Pemetrexed: C1D1, D2, D3 - Cisplatin: C1D1, D2, D3]
Tumor response evaluation following mRECIST criteria to determine the number of patients with CR, PR, SD or PD [Time Frame: Baseline, every 8 weeks up to cycle 12; then every 12 weeks from cycle 13 up to 2 years, or until discontinuation of study treatment, whichever comes first]
Number of patients with a positive titer of anti-drug antibodies [Time Frame: Day1 of C1, C3, C6 and subsequent cycles every 3rd cycle up to 2 years or until discontinuation of study treatment, whichever comes first]
|Study Arms / Comparison Groups||1 / 0|
|Recruitment Status||Active, not recruiting|
|Ages||18 Years - N/A|
|Accepts Healthy Volunteers||No|
- Subjects may be male or female, and must be aged =/>18 years on the date of signing the informed consent form.
- Subjects must have histologically confirmed, unresectable, locally advanced or metastatic pleural or peritoneal predominantly (>50% of tumor component) epithelial mesothelioma or nonsquamous non-small-cell lung cancer (NSCLC). Both chemotherapy-naive and previously treated subjects will be eligible; however, newly diagnosed NSCLC subjects eligible for FDA-approved therapies should have received the same before enrollment (e.g. subjects with epidermal growth factor receptor [EGFR]-mutated and anaplastic lymphoma kinase [ALK]-translocated NSCLC should have received FDA-approved targeted therapies).
- Subjects must have at least 1 measurable or evaluable tumor lesion according to RECIST 1.1 (for nonsquamous NSCLC) or mRECIST (for epithelial pleural mesothelioma). Subjects with resected primary tumors who have documented metastases are eligible.
- Subjects must have a life expectancy of at least 12 weeks.
- Subjects must have ECOG (Eastern Cooperative Oncology Group performance Status of 0 or 1
- Subjects must have adequate bone marrow, liver, kidney, and coagulation functions.
- Subjects who have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, or any previous cancer curatively treated >3 years before the start of study Treatment.
- Subjects who have a history or current evidence of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE (Common Terminology Criteria for Adverse Events) Grade ≥2 within 4 weeks before the start of study Treatment.
- Subjects who have new or progressive brain or meningeal or spinal metastases.
- Subjects who have a history or current evidence of uncontrolled cardiovascular disease i.e. NYHA (New York Heart Association) Class III or IV.
- Subjects who have a history or current evidence of uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at screening despite optimal medical management.
- Subjects who have a history or current evidence of malignant biliary obstruction requiring biliary stent.
- Subjects who have had solid organ or bone marrow Transplantation.
- Subjects who have a history of hypersensitivity to any of the study drugs or their excipients, or a history of severe hypersensitivity to any other Antigen.
- Subjects who have a history of human immunodeficiency virus (HIV) infection or subjects who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
- Subjects who have an active clinically serious infection of CTCAE Grade ≥2 or non-healing wound unrelated to the primary Tumor.
- Subjects who have received systemic cancer therapy, radiotherapy, investigational drug treatment outside of this study within 4 weeks before the start of study treatment, granulocyte colony stimulating factors, (G-CSF) or granulocyte macrophage-stimulating factors (GM-CSF), erythropoietin-stimulating agents within 3 weeks before the start of general screening, drugs with known renal toxicity and strong cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers within 2 weeks before the treatment.
- Subjects who have started oral or parenteral anticoagulation therapy within 2 weeks before the start of anetumab ravtansine until end of treatment visit.
|Verification Date||July 2018|