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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02610140




Registration number
NCT02610140
Ethics application status
Date submitted
9/11/2015
Date registered
20/11/2015
Date last updated
17/07/2020

Titles & IDs
Public title
Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)
Scientific 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
Secondary ID [1] 0 0
2012-003650-88
Secondary ID [2] 0 0
15743
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mesothelioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Anetumab ravtansine (BAY94-9343)
Treatment: Drugs - Vinorelbine

Experimental: BAY94-9343 - Drug Anetumab ravtansine given Intravenously (IV)

Active Comparator: Vinorelbine - Drug Vinorelbine given Intravenously


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS), [95% CI] - 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.
Timepoint [1] 0 0
From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017)
Secondary outcome [1] 0 0
Overall Survival (OS), [95% CI] - Overall survival (OS) was defined as time from randomization until death from any cause.
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Objective Response Rate (ORR) - 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.
Timepoint [2] 0 0
up to approx. 30 months (data cut-off: 31-May-2017) - Time from randomization until death from any cause.
Secondary outcome [3] 0 0
Disease Control Rate (DCR) - 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.
Timepoint [3] 0 0
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Secondary outcome [4] 0 0
Duration of Response (DOR) - 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.
Timepoint [4] 0 0
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Secondary outcome [5] 0 0
Durable Response Rate (DRR) - 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.
Timepoint [5] 0 0
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Secondary outcome [6] 0 0
Percentage of Participants With Confirmed Improvement of Symptoms Characteristic of Mesothelioma - 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.
Timepoint [6] 0 0
up to approx. 30 months (data cut-off: 31-May-2017)
Secondary outcome [7] 0 0
Time to Worsening of Symptoms Characteristic of Mesothelioma - 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.
Timepoint [7] 0 0
up to approx. 30 months (data cut-off: 31-May-2017)
Secondary outcome [8] 0 0
Time to Worsening of Pain - 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.
Timepoint [8] 0 0
up to approx. 30 months (data cut-off: 31-May-2017)
Secondary outcome [9] 0 0
Percentage of Participants With Confirmed Improvement of Pain - 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.
Timepoint [9] 0 0
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Secondary outcome [10] 0 0
Percentage of Participant With Treatment-emergent Adverse Events (TEAEs) - TEAEs were defined as all AEs starting or worsening within the treatment period.
Timepoint [10] 0 0
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
Secondary outcome [11] 0 0
Number of Deaths - TEAE(s) associated with a fatal outcome (CTCAE Grade 5) at the time of the data cut-off 06-Apr-2018.
Timepoint [11] 0 0
Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
- St Leonards
Recruitment hospital [2] 0 0
- Woolloogabba
Recruitment hospital [3] 0 0
- Adelaide
Recruitment hospital [4] 0 0
- Richmond
Recruitment hospital [5] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4102 - Woolloogabba
Recruitment postcode(s) [3] 0 0
5043 - Adelaide
Recruitment postcode(s) [4] 0 0
3122 - Richmond
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Belgium
State/province [13] 0 0
Bruxelles - Brussel
Country [14] 0 0
Belgium
State/province [14] 0 0
Edegem
Country [15] 0 0
Belgium
State/province [15] 0 0
Gent
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Belgium
State/province [17] 0 0
Liege
Country [18] 0 0
Belgium
State/province [18] 0 0
Sint-niklaas
Country [19] 0 0
Canada
State/province [19] 0 0
Alberta
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Finland
State/province [21] 0 0
Helsinki
Country [22] 0 0
Finland
State/province [22] 0 0
Turku
Country [23] 0 0
Finland
State/province [23] 0 0
Vaasa
Country [24] 0 0
France
State/province [24] 0 0
Bordeaux Cedex
Country [25] 0 0
France
State/province [25] 0 0
Caen Cedex 5
Country [26] 0 0
France
State/province [26] 0 0
Lille Cedex
Country [27] 0 0
France
State/province [27] 0 0
Marseille
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
France
State/province [29] 0 0
Pierre Benite
Country [30] 0 0
Italy
State/province [30] 0 0
Friuli-Venezia Giulia
Country [31] 0 0
Italy
State/province [31] 0 0
Lombardia
Country [32] 0 0
Italy
State/province [32] 0 0
Piemonte
Country [33] 0 0
Italy
State/province [33] 0 0
Toscana
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Netherlands
State/province [35] 0 0
Amsterdam
Country [36] 0 0
Netherlands
State/province [36] 0 0
Rotterdam
Country [37] 0 0
Poland
State/province [37] 0 0
Gdansk
Country [38] 0 0
Poland
State/province [38] 0 0
Krakow
Country [39] 0 0
Poland
State/province [39] 0 0
Szczecin
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Omsk
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Yekaterinburg
Country [42] 0 0
Spain
State/province [42] 0 0
A Coruña
Country [43] 0 0
Spain
State/province [43] 0 0
Alicante
Country [44] 0 0
Spain
State/province [44] 0 0
Barcelona
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Málaga
Country [47] 0 0
Turkey
State/province [47] 0 0
Adana
Country [48] 0 0
Turkey
State/province [48] 0 0
Ankara
Country [49] 0 0
Turkey
State/province [49] 0 0
Eskisehir
Country [50] 0 0
Turkey
State/province [50] 0 0
Istanbul
Country [51] 0 0
Turkey
State/province [51] 0 0
Malatya
Country [52] 0 0
Turkey
State/province [52] 0 0
Yenimahalle
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Devon
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Kent
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Leicestershire
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Glasgow
Country [57] 0 0
United Kingdom
State/province [57] 0 0
London
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Manchester
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
ImmunoGen and MorphoSys
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02610140
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications