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MesotheliomaPhase 2NCT02610140

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

A Phase 2 study testing Anetumab ravtansine (BAY94-9343) and Vinorelbine in people with Mesothelioma, run by Bayer at 75 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mesothelioma
What is being tested?
Anetumab ravtansine (BAY94-9343) and Vinorelbine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
248 participants
Where
75 sitesin 14 countries
Study dates
3 Dec 2015to 6 Sep 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

75 sites in 14 countries.

75 sites in 14 countries

United States15 sites

  • Study site

    Aurora, Colorado, 80045

  • Study site

    Bethesda, Maryland, 20814

  • Study site

    Buffalo, New York, 14263-0001

  • Study site

    Chicago, Illinois, 60612

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Cleveland, Ohio, 44195

  • Study site

    Dallas, Texas, 75251

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Houston, Texas, 77030

  • Study site

    La Jolla, California, 92093-1503

  • Study site

    New Orleans, Louisiana, 70121

  • Study site

    New York, New York, 10016

  • Study site

    Norwich, Connecticut, 06360

  • Study site

    Rochester, Minnesota, 55905

  • Study site

    Tampa, Florida, 33612

Other trials in United States

France7 sites

  • Study site

    Bordeaux, 33076

  • Study site

    Caen, 14076

  • Study site

    Lille, 59037

  • Study site

    Marseille, 13915

  • Study site

    Paris, 75018

  • Study site

    Paris, 75020

  • Study site

    Pierre-Bénite, 69495

Other trials in France

Italy7 sites

  • Study site

    Bergamo, Lombardy, 24125

  • Study site

    Milan, Lombardy, 20089

  • Study site

    Milan, Lombardy, 20133

  • Study site

    Monza Brianza, Lombardy, 20900

  • Study site

    Pordenone, Friuli Venezia Giulia, 33081

  • Study site

    Siena, Tuscany, 53100

  • Study site

    Turin, Piedmont, 10043

Other trials in Italy

United Kingdom7 sites

  • Study site

    Glasgow, G12 0YN

  • Study site

    Leicester, Leicestershire, LE1 5WW

  • Study site

    London, SE1 9RT

  • Study site

    Maidstone, Kent, ME16 9QQ

  • Study site

    Manchester, M23 9LT

  • Study site

    Newcastle upon Tyne, NE7 7DN

  • Study site

    Plymouth, Devon, PL6 8DH

Other trials in United Kingdom

Belgium6 sites

  • Study site

    Bruxelles - Brussel, 1200

  • Study site

    Edegem, 2650

  • Study site

    Ghent, 9000

  • Study site

    Leuven, 3000

  • Study site

    Liège, 4000

  • Study site

    Sint-Niklaas, 9100

Other trials in Belgium

Turkey (Türkiye)6 sites

  • Study site

    Adana, 01330

  • Study site

    Ankara, 06100

  • Study site

    Eskişehir, 26480

  • Study site

    Istanbul, 34899

  • Study site

    Malatya, 44280

  • Study site

    Yenimahalle, 06200

Other trials in Turkey (Türkiye)

Australia5 sites

  • Study site

    Adelaide, South Australia, 5043

  • Study site

    Nedlands, Western Australia, 6009

  • Study site

    Richmond, Victoria, 3122

  • Study site

    St Leonards, New South Wales, 2065

  • Study site

    Woolloogabba, Queensland, 4102

Other trials in Australia

Spain5 sites

  • Study site

    A Coruña, 15006

  • Study site

    Alicante, 03010

  • Study site

    Barcelona, 08035

  • Study site

    Madrid, 28041

  • Study site

    Málaga, 29010

Other trials in Spain

Canada4 sites

  • Study site

    Calgary, Alberta, T2N 4N2

  • Study site

    Hamilton, Ontario, L8V 5C2

  • Study site

    London, Ontario, N6A 4L6

  • Study site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Poland4 sites

  • Study site

    Gdansk, 80-952

  • Study site

    Krakow, 31-202

  • Study site

    Krakow, 31-501

  • Study site

    Szczecin, 70-891

Other trials in Poland

Finland3 sites

  • Study site

    Helsinki, 00290

  • Study site

    Turku, 20520

  • Study site

    Vaasa, 65130

Other trials in Finland

Netherlands2 sites

  • Study site

    Amsterdam, 1066 CX

  • Study site

    Rotterdam, 3015 CE

Other trials in Netherlands

Russia2 sites

  • Study site

    Omsk, 644013

  • Study site

    Yekaterinburg, 620036

Other trials in Russia

South Korea2 sites

  • Study site

    Seoul, 05505

  • Study site

    Seoul, 06351

Other trials in South Korea

About this study

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

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.

Read more

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.

Conditions
Mesothelioma
Being tested
Anetumab ravtansine (BAY94-9343), Vinorelbine
Medical subject headings
Mesothelioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • VinorelbineDrug

    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 groups in NCT02610140
Study groupRoleWhat they receive
BAY94-9343ExperimentalDrug Anetumab ravtansine given Intravenously (IV)
Receives: Drug: Anetumab ravtansine (BAY94-9343)
VinorelbineActive comparatorDrug Vinorelbine given Intravenously
Receives: Drug: Vinorelbine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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. Only descriptive analysis of OS was repeated in the follow-up period.

    Measured: From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017)

Secondary outcomes (12)

  1. Overall Survival (OS), [95% CI]

    Overall survival (OS) was defined as time from randomization until death from any cause.

    Measured: 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.

  2. 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.

    Measured: up to approx. 30 months (data cut-off: 31-May-2017) - Time from randomization until death from any cause.

  3. 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.

    Measured: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

  4. 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.

    Measured: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

  5. 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.

    Measured: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

  6. 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.

    Measured: up to approx. 30 months (data cut-off: 31-May-2017)

  7. 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.

    Measured: up to approx. 30 months (data cut-off: 31-May-2017)

  8. 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.

    Measured: up to approx. 30 months (data cut-off: 31-May-2017)

  9. 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.

    Measured: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

  10. Percentage of Participant With Treatment-emergent Adverse Events (TEAEs)

    TEAEs were defined as all AEs starting or worsening within the treatment period.

    Measured: 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).

  11. Number of Deaths

    TEAE(s) associated with a fatal outcome (CTCAE Grade 5) at the time of the data cut-off 06-Apr-2018.

    Measured: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

  12. Overall Survival (OS) - Addendum

    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.

    Measured: Up to approx. 55 month (data cut-off: 02-JUL-2019) - Time from randomization until death from any cause

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2015 (estimated)
  2. Study start3 Dec 2015
  3. Primary completion31 May 2017
  4. Study completion6 Sep 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
248 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02610140
Sponsor's protocol ID
15743
Other IDs
2012-003650-88
Status last verified
Oct 2020
First submitted
9 Nov 2015
Last updated
4 Nov 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 35358455

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anetumab ravtansine (BAY94-9343) and Vinorelbine in people with Mesothelioma, run by Bayer at 75 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 75 sites in United States, France, Italy, United Kingdom, Belgium and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02610140, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2020.

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