Clinical trial NCT02610140: Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mesothelioma
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: ImmunoGen and MorphoSys
First posted: 2015-11-20
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Progression-free Survival (PFS), [95% CI]
timeFrame: From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017)
Secondary outcomes:
measure: Overall Survival (OS), [95% CI]
timeFrame: 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.
measure: Objective Response Rate (ORR)
timeFrame: up to approx. 30 months (data cut-off: 31-May-2017) - Time from randomization until death from any cause.
measure: Disease Control Rate (DCR)
timeFrame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
measure: Duration of Response (DOR)
timeFrame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
measure: Durable Response Rate (DRR)
timeFrame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
measure: Percentage of Participants With Confirmed Improvement of Symptoms Characteristic of Mesothelioma
timeFrame: up to approx. 30 months (data cut-off: 31-May-2017)
measure: Time to Worsening of Symptoms Characteristic of Mesothelioma
timeFrame: up to approx. 30 months (data cut-off: 31-May-2017)
measure: Time to Worsening of Pain
timeFrame: up to approx. 30 months (data cut-off: 31-May-2017)
measure: Percentage of Participants With Confirmed Improvement of Pain
timeFrame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
measure: Percentage of Participant With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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).
measure: Number of Deaths
timeFrame: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.
measure: Overall Survival (OS) - Addendum
timeFrame: Up to approx. 55 month (data cut-off: 02-JUL-2019) - Time from randomization until death from any cause
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Norwich
country: United States
state: Connecticut
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: New Orleans
country: United States
state: Louisiana
city: Bethesda
country: United States
state: Maryland
city: Rochester
country: United States
state: Minnesota
city: Buffalo
country: United States
state: New York
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: St Leonards
country: Australia
state: New South Wales
city: Woolloogabba
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Richmond
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Bruxelles - Brussel
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Sint-niklaas
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Helsinki
country: Finland
city: Turku
country: Finland
city: Vaasa
country: Finland
city: Bordeaux Cedex
country: France
city: Caen Cedex 5
country: France
city: Lille Cedex
country: France
city: Marseille
country: France
city: Paris
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Pordenone
country: Italy
state: Friuli-Venezia Giulia
city: Bergamo
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Monza Brianza
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Siena
country: Italy
state: Toscana
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Amsterdam
country: Netherlands
city: Rotterdam
country: Netherlands
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Krakow
country: Poland
city: Szczecin
country: Poland
city: Omsk
country: Russian Federation
city: Yekaterinburg
country: Russian Federation
city: A Coruña
country: Spain
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Adana
country: Turkey
city: Ankara
country: Turkey
city: Eskisehir
country: Turkey
city: Istanbul
country: Turkey
city: Malatya
country: Turkey
city: Yenimahalle
country: Turkey
city: Plymouth
country: United Kingdom
state: Devon
city: Maidstone
country: United Kingdom
state: Kent
city: Leicester
country: United Kingdom
state: Leicestershire
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Kindler HL, Novello S, Bearz A, Ceresoli GL, Aerts JGJV, Spicer J, Taylor P, Nackaerts K, Greystoke A, Jennens R, Calabro L, Burgers JA, Santoro A, Cedres S, Serwatowski P, Ponce S, Van Meerbeeck JP, Nowak AK, Blumenschein G Jr, Siegel JM, Kasten L, Kochert K, Walter AO, Childs BH, Elbi C, Hassan R, Fennell DA. Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial. Lancet Oncol. 2022 Apr;23(4):540-552. doi: 10.1016/S1470-2045(22)00061-4.