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

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ClinicalTrials.gov Identifier: NCT02610140
Recruitment Status : Completed
First Posted : November 20, 2015
Results First Posted : July 17, 2020
Last Update Posted : November 4, 2020
Sponsor:
Collaborator:
ImmunoGen and MorphoSys
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE November 9, 2015
First Posted Date  ICMJE November 20, 2015
Results First Submitted Date  ICMJE May 22, 2020
Results First Posted Date  ICMJE July 17, 2020
Last Update Posted Date November 4, 2020
Actual Study Start Date  ICMJE December 3, 2015
Actual Primary Completion Date May 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 18, 2015)
Progression Free Survival [ Time Frame: Approx. 24 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2020)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2015)
  • 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.
  • Forced vital capacity (FVC) response [ Time Frame: Assessed from randomization until disease progression, up to 48 months ]
    An improvement of ≥ 30% FVC is defined as PR (partial response), an improvement of < 30% to a deterioration of < 20% is defined as no change (NC), and a deterioration of ≥ 20% is defined as PD (progressive disease). Forced vital capacity (FVC) as a measure of pulmonary function in chemotherapy pre-treated patients will be evaluated by a spirometry machine.
  • Patient-reported outcomes (PROs) [ Time Frame: Approx. 24 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).
  • Objective response rate (ORR) [ Time Frame: Assessed from randomization until disease progression, up to 48 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.
  • Duration of Response (DOR) [ Time Frame: Up to 24 months ]
    Defined as proportion of patients achieving CR, PR, or (Stable disease) SD per mRECIST criteria, as determined by the central radiological reviewer.
  • Number of participants with treatment emergent adverse events as a measure of safety and tolerability [ Time Frame: Up to 24 months ]
  • Number of participants with serious adverse events as a measure of safety and tolerability [ Time Frame: Up to 24 months ]
  • Disease control rate (DCR) [ Time Frame: Up to 24 months ]
    Defined as proportion of patients achieving CR, PR, or (Stable disease) SD per mRECIST criteria, as determined by the central radiological reviewer.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mesothelioma
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: BAY94-9343
    Drug Anetumab ravtansine given Intravenously (IV)
    Intervention: Drug: Anetumab ravtansine (BAY94-9343)
  • Active Comparator: Vinorelbine
    Drug Vinorelbine given Intravenously
    Intervention: Drug: Vinorelbine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 13, 2017)
248
Original Estimated Enrollment  ICMJE
 (submitted: November 18, 2015)
183
Actual Study Completion Date  ICMJE September 6, 2019
Actual Primary Completion Date May 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Finland,   France,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT02610140
Other Study ID Numbers  ICMJE 15743
2012-003650-88 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE ImmunoGen and MorphoSys
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP