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Completed

NCT Number: NCT02610140

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

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.

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Key information

Conditions

Mesothelioma Adenoma Neoplasms Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

St Leonards, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Anetumab ravtansine (BAY94-9343)

Drug

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.

Vinorelbine

Drug

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 outcomes

  1. 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 outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Collaborators

  • ImmunoGen and MorphoSys

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2017
Study completion
2019
First posted
Nov 20, 2015
Registry last updated
Nov 4, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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