Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)
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| ClinicalTrials.gov Identifier: NCT02610140 |
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Recruitment Status :
Completed
First Posted : November 20, 2015
Results First Posted : July 17, 2020
Last Update Posted : November 4, 2020
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Sponsor:
Bayer
Collaborator:
ImmunoGen and MorphoSys
Information provided by (Responsible Party):
Bayer
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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 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 (BAY94-9343) Drug: Vinorelbine | Phase 2 |
| 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 |
| Actual Study Completion Date : | September 6, 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Mesothelioma
| Arm | Intervention/treatment |
|---|---|
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Experimental: BAY94-9343
Drug Anetumab ravtansine given Intravenously (IV)
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Drug: Anetumab ravtansine (BAY94-9343)
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. |
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Active Comparator: Vinorelbine
Drug Vinorelbine given Intravenously
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Drug: Vinorelbine
Starting dose: 30mg/m^2 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. |
Primary Outcome Measures :
- Progression-free Survival (PFS), [95% CI] [ Time Frame: From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017) ]Progression-free survival (PFS), defined as time from randomization until disease progression according to mRECIST (Modified Response Evaluation Criteria in Solid Tumors) for Malignant pleural mesothelioma (MPM) per blinded central radiology review, or death. Only descriptive analysis of OS was repeated in the follow-up period.
Secondary Outcome Measures :
- Overall Survival (OS), [95% CI] [ Time Frame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause; one-sided log-rank test stratified by time to progression (TTP) on first line treatment. ]Overall survival (OS) was defined as time from randomization until death from any cause.
- Objective Response Rate (ORR) [ Time Frame: up to approx. 30 months (data cut-off: 31-May-2017) - Time from randomization until death from any cause. ]A patient is a responder if the patient has a confirmed best tumor response on-study of CR (Complete response) or PR (Partial response), as determined by the central radiological reviewer per mRECIST criteria. ORR in each treatment arm was defined as the number of responders divided by the number of randomized patients. A responder was a patient who had a confirmed best tumor response on-study of CR or PR, as determined by the central radiological reviewer per mRECIST criteria.
- Disease Control Rate (DCR) [ Time Frame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause. ]A patient has disease control if the patient has a best tumor response on-study of CR, PR, or SD (Stable disease). DCR was defined as a percentage of patients achieving CR, PR, or SD per mRECIST criteria, as determined by the central radiological reviewer. DCR was calculated in each treatment arm as the number of patients with disease control (a best tumor response on-study of CR, PR, or SD) divided by the number of randomized patients.
- Duration of Response (DOR) [ Time Frame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause. ]DOR was defined in responders as the time from central documentation of tumor response date of first response in the confirmation sequence) to the earlier of disease progression as determined by the central radiological reviewer, or death without centrally documented progression. A responder was a patient who had a confirmed best tumor response on-study of CR or PR, as determined by the central radiological reviewer per mRECIST criteria.
- Durable Response Rate (DRR) [ Time Frame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause. ]A durable responder was a responder (i.e. confirmed best tumor response on study of CR or PR) with duration of response of 180 days or more.
- Percentage of Participants With Confirmed Improvement of Symptoms Characteristic of Mesothelioma [ Time Frame: up to approx. 30 months (data cut-off: 31-May-2017) ]Improvement rate of symptoms characteristic of mesothelioma was defined as the number of patients with confirmed improvement of symptoms characteristic of mesothelioma (based on the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma, MDASI-MPM), divided by the number of patients evaluable for improvement of symptoms characteristic of mesothelioma.
- Time to Worsening of Symptoms Characteristic of Mesothelioma [ Time Frame: up to approx. 30 months (data cut-off: 31-May-2017) ]Time to worsening of symptoms characteristic of mesothelioma (TTWS) was defined in patients evaluable for assessing worsening of symptoms, as the time from randomization until the first worsening of symptoms characteristic of mesothelioma. Patients who died, were lost to follow-up, or ended (MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma) MDASI-MPM assessments without confirmed worsening of symptoms were censored at the date of their last MDASI-MPM assessment with a non-missing (Composite Symptom Score) CSS.
- Time to Worsening of Pain [ Time Frame: up to approx. 30 months (data cut-off: 31-May-2017) ]Time to worsening of pain (TTWP) was defined in patients evaluable for assessing worsening of pain, as time from randomization until the first worsening of pain. Patients who died, were lost to follow-up, or ended (MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma) MDASI-MPM assessments without confirmed worsening of pain were censored at the date of their last MDASI-MPM assessment with a non-missing pain score.
- Percentage of Participants With Confirmed Improvement of Pain [ Time Frame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause. ]Improvement rate of pain was defined as the number of patients with confirmed improvement of pain (based on the "pain at its worst" item of MDASI-MPM), divided by the number of patients evaluable for improvement of pain.
- Percentage of Participant With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to approx. 55 months (data cut-off: 02-Jul-2019) - Time from randomization until 30 days after last treatment (general AEs), or further until death from any cause (selected AEs). ]TEAEs were defined as all AEs starting or worsening within the treatment period.
- Number of Deaths [ Time Frame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause. ]TEAE(s) associated with a fatal outcome (CTCAE Grade 5) at the time of the data cut-off 06-Apr-2018.
- Overall Survival (OS) - Addendum [ Time Frame: Up to approx. 55 month (data cut-off: 02-JUL-2019) - Time from randomization until death from any cause ]Overall survival (OS) was defined as time from randomization until death from any cause; Only descriptive analyses of OS were repeated in with the data as of the 02 JUL 2019.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| 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 investigator in consultation with 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02610140
Locations
Show 75 study locations
Sponsors and Collaborators
Bayer
ImmunoGen and MorphoSys
Investigators
| Study Director: | Bayer Study Director | Bayer |
Study Documents (Full-Text)
Documents provided by Bayer:
Documents provided by Bayer:
Study Protocol [PDF] March 27, 2018
Statistical Analysis Plan [PDF] April 18, 2018
Additional Information:
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT02610140 |
| Other Study ID Numbers: |
15743 2012-003650-88 ( EudraCT Number ) |
| First Posted: | November 20, 2015 Key Record Dates |
| Results First Posted: | July 17, 2020 |
| Last Update Posted: | November 4, 2020 |
| Last Verified: | October 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Mesothelioma Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Mesothelial Vinorelbine |
Maytansine Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |