The main purpose of the 15743 study is to assess efficacy and safety of anetumab ravtansine versus vinorelbine in progression free survival in patients with stage IV mesothelin overexpressing malignant pleural mesothelioma (MPM).
210 eligible patients will be randomized to receive either anetumab ravtansine every three weeks or weekly vinorelbine.
Treatment will continue until centrally confirmed disease progression (PD) or until another criterion is met for withdrawal from the study. Patients will enter follow up phase to capture safety and endpoint data as required.
Efficacy will be measured by evaluating progression free survival from randomization. Radiological tumor assessments will be performed at defined time points until the patient's disease progresses.
Blood samples will be collected for safety, pharmacokinetic and biomarker analysis. Archival or fresh biopsy tissue may also be collected for central pathology review and biomarkers.
|First Received Date||November 9, 2015|
|Last Changed Date||February 13, 2017|
|Start Date||December 2015|
|Anticipated Primary Completion Date||November 2017|
|Primary Outcome Measures||
Progression Free Survival [Time Frame: Approx. 22 months]
|Secondary Outcome Measures||
Overall survival (OS) [Time Frame: Approx. 42 months]
Patient-reported outcomes (PROs) [Time Frame: Approx. 22 months]
Objective response rate (ORR) [Time Frame: Approx. 22 months]
Duration of response (DOR) [Time Frame: Approx. 42 months]
Number of participants with treatment emergent adverse events as a measure of safety and tolerability [Time Frame: Approx. 22 months]
Number of participants with serious adverse events as a measure of safety and tolerability [Time Frame: Approx. 22 months]
Disease control rate (DCR) [Time Frame: Approx. 22 months]
Durable Response Rate (DRR) [Time Frame: Approx. 42 months]
|Study Arms / Comparison Groups||2 / 0|
|Recruitment Status||Active, not recruiting|
|Ages||18 Years - N/A|
|Accepts Healthy Volunteers||No|
- Histological documentation of malignant pleural mesothelioma (MPM) overexpressing mesothelin
- Unresectable locally advanced or metastatic MPM after locally confirmed progression on 1st line treatment with platinum in combination with pemetrexed.
- Patients must have measurable disease
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Life expectancy of at least 3 months.
- Adequate bone marrow, liver and renal function
- Left ventricular ejection fraction (LVEF) ≥ 50% or the lower limit of normal (LLN) according to local institution ranges of normality.
- More than 1 previous systemic anti-cancer therapy line
- Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the ophthalmologist.
- Brain metastases, meningeal tumours or other metastases in the central nervous system
- Evidence of history of bleeding diathesis.
- Ongoing or active infection (bacterial, fungal, or viral) of National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade > 2.
- Pre-existing cardiac conditions
|Verification Date||February 2017|