Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Mesothelioma	Drug: Anetumab ravtansine (BAY 94-9343); Drug: Vinorelbine	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	248 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Randomized, Open-label, Active-controlled, Phase II Study of Intravenous Anetumab Ravtansine (BAY 94-9343) or Vinorelbine in Patients With Advanced or Metastatic Malignant Pleural Mesothelioma Overexpressing Mesothelin and Progressed on First Line Platinum/Pemetrexed-based Chemotherapy
Actual Study Start Date :	December 3, 2015
Actual Primary Completion Date :	May 31, 2017
Estimated Study Completion Date :	July 29, 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: BAY 94-9343; Drug Anetumab ravtansine given Intravenously (IV)	Drug: Anetumab ravtansine (BAY 94-9343); Starting dose: 6.5 mg/kg administered as IV infusion over 1 h every 3 weeks until disease progression or treatment withdrawal for any reason. Dose reductions are permitted.
Active Comparator: Vinorelbine; Drug Vinorelbine given Intravenously	Drug: Vinorelbine; Starting dose: 30mg/m² administered as an IV infusion over 6 to 10 min every week until disease progression or treatment withdrawal for any reason. Dose reductions are permitted per standard practise.

Outcome Measures

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Primary Outcome Measures :

1. Progression Free Survival [ Time Frame: Approx. 22 months ]
   Defined as time from randomization until disease progression or death. Patients not experiencing death or progression will be censored at the last tumor assessment.

Secondary Outcome Measures :

1. Overall survival (OS) [ Time Frame: Approx. 42 months ]
   Defined as time from randomization until death from any cause. Patients lost to follow-up or alive at the time of analysis will be censored at the last known alive date.
2. Patient-reported outcomes (PROs) [ Time Frame: Approx. 22 months ]
   PROs: Time to worsening of symptoms characteristic of mesothelioma, time to worsening of pain, time to improvement of symptoms characteristic of mesothelioma and time to improvement of pain. Symptoms will be assessed using the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma (MDASI-MPM) and the Lung Cancer Symptom Scale-Mesothelioma (LCSS-Meso).
3. Objective response rate (ORR) [ Time Frame: Approx. 22 months ]
   A patient is a responder if the patient has a confirmed tumor response on-study of (complete response) CR or PR, as determined by the central radiological reviewer per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria for MPM. The ORR in each arm is the number of responders divided by the number of randomized patients.
4. Duration of response (DOR) [ Time Frame: Approx. 42 months ]
   Defined as proportion of patients achieving CR, PR, or (Stable disease) SD per mRECIST criteria, as determined by the central radiological reviewer.
5. Number of participants with treatment emergent adverse events as a measure of safety and tolerability [ Time Frame: Approx. 22 months ]
6. Number of participants with serious adverse events as a measure of safety and tolerability [ Time Frame: Approx. 22 months ]
7. Disease control rate (DCR) [ Time Frame: Approx. 22 months ]
   Defined as proportion of patients achieving CR, PR, or (Stable disease) SD per mRECIST criteria, as determined by the central radiological reviewer.
8. Durable Response Rate (DRR) [ Time Frame: Approx. 42 months ]
   Defined in responders as a responder with a duration of response of 180 days or more as determined by the central radiological reviewer.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 75 Study Locations

Sponsors and Collaborators

Bayer

ImmunoGen and MorphoSys

Investigators

Study Director:	Bayer Study Director	Bayer

More Information

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Additional Information:

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Responsible Party:	Bayer
ClinicalTrials.gov Identifier:	NCT02610140 History of Changes
Other Study ID Numbers:	15743; 2012-003650-88 ( EudraCT Number )
First Posted:	November 20, 2015
Last Update Posted:	March 27, 2018
Last Verified:	March 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Vinorelbine; Vinblastine; Maytansine	Immunoconjugates; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Physiological Effects of Drugs