check_circleStudy Completed

Neoplasms

Bayer Identifier:

15834

ClinicalTrials.gov Identifier:

NCT03102320

EudraCT Number:

2016-004002-33

EU CT Number:

Not Available
Phase 1b multi-indication study of anetumab ravtansine in mesothelin expressing advanced solid tumors

Trial purpose

The key purpose of the main part of the study is to assess efficacy and safety of anetumab ravtansine as monotherapy or combination therapy for mesothelin expressing advanced solid tumors.

The main purpose of the safety lead-in (dose-finding) part of the study is to determine the safety and tolerability of anetumab ravtansine in combination with cisplatin and in combination with gemcitabine, and to determine the MTD of anetumab ravtansine in combination with cisplatin for mesothelin expressing advanced cholangiocarcinoma and in combination with gemcitabine for mesothelin expressing advanced adenocarcinoma of the pancreas.

Patients will receive anetumab ravtansine every three weeks in monotherapy for most indications. In cholangiocarinoma and adenocarinoma of the pancreas, 3-weekly anetumab ravtansine is administered in combination with cisplatin or gemcitabine respectively (both administered in a 2 week on / 1 week off schedule).

Treatment will continue until disease progression or until another criterion for withdrawal is met. .Efficacy will be measured by evaluating the tumor's objective response rate. 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 will also be collected for mesothelin expression testing and biomarker analyses.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - Availability of tumor tissue for mesothelin expression testing and for further biomarker analysis
    - Histologically-confirmed, mesothelin-expressing metastatic or advanced non-metastatic disease (tumour type specific inclusion criteria)
    - At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (or for thymic carcinoma, at least one measurable lesion per International Thymic Malignancy Interest Group (ITMIG) modified RECIST 1.1 criteria
    - Adequate bone marrow, liver, renal and coagulation function
    - Left ventricular ejection fraction (LVEF) ≥ 50% of the lower limit of normal (LLN) according to local institutional ranges
    - Eastern Cooperative Oncology Group (ECOG) 0 or 1


  • - Exposure to more than one prior anti-tubulin/microtubule agent
    - Corneal epitheliopathy or any eye disorder that may predispose the patients to this condition
    - Symptomatic Central nervous system (CNS) metastases and/or carcinomatous meningitis
    - Contraindication to both CT and MRI contrast agents
    - Active hepatitis B or C infection
    - Pregnant or breast-feeding patients
    - Tumor type specific exclusion criteria

Trial summary

Enrollment Goal
173
Trial Dates
May 2017 - July 2021
Phase
Phase 1
Could I Receive a placebo
No
Products
Anetumab ravtansine (BAY94-9343)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
UZ AntwerpenEDEGEM, 2650, Belgium
Completed
CHU de LiègeLIEGE, 4000, Belgium
Withdrawn
GZA ZiekenhuizenWilrijk, 2610, Belgium
Completed
Hôpital Erasme/Erasmus ZiekenhuisBRUXELLES - BRUSSEL, 1070, Belgium
Completed
UZ Leuven GasthuisbergLEUVEN, 3000, Belgium
Withdrawn
Yale Cancer CenterNew Haven, 06510, United States
Withdrawn
University of Michigan Health SystemAnn Arbor, 48109-0330, United States
Completed
MedStar Georgetown University HospitalWashington, 20007, United States
Completed
National Cancer Institute - MarylandBethesda, 20892, United States
Completed
National University HospitalSingapore, 119228, Singapore
Completed
National Cancer Center SingaporeSingapore, 169610, Singapore
Withdrawn
Universitätsklinikum EssenEssen, 45239, Germany
Withdrawn
Kliniken Nord und SüdNürnberg, 90419, Germany
Completed
University of Texas MD Anderson Cancer CenterHouston, 77030, United States
Completed
Ciutat Sanitària i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Completed
Centro Integral Oncológico Clara CampalMadrid, 28050, Spain
Completed
Hospital Ramón y Cajal | OncologíaMadrid, 28034, Spain
Completed
Hospital Virgen de la VictoriaMálaga, 29010, Spain
Completed
Hospital Clínic i Provincial de BarcelonaBarcelona, 08036, Spain
Completed
Hospital Universitario 12 de OctubreMadrid, 28041, Spain
Withdrawn
Institut Català d'Oncologia HospitaletL'Hospitalet de Llobregat, 08907, Spain
Completed
Mayo Clinic HospitalPhoenix, 85054-4502, United States
Completed
Vanderbilt University Medical CenterNashville, 37232, United States
Completed
Blacktown Cancer & Haematology CentreBlacktown, 2148, Australia
Completed
St John of God HealthcareSubiaco, 6008, Australia
Completed
Sir Charles Gairdner HospitalNedlands, 6009, Australia
Completed
Kinghorn Cancer CentreDarlinghurst, 2010, Australia
Completed
St John of God HealthcareSubiaco, 6008, Australia
Completed
Hopital Jean MinjozBESANCON, 25030, France
Completed
Hôpital Henri MondorCRETEIL, 94010, France
Completed
Centre Oscar Lambret - LilleLILLE CEDEX, 59020, France
Completed
Centre Hospitalier Lyon SudPIERRE BENITE, 69495, France
Completed
C.H.U. TimoneMarseille, 13385, France
Completed
Centre René GauducheauNantes, 44805, France
Withdrawn
Städt. Klinikum MünchenMünchen, 81737, Germany
Withdrawn
Marienhospital Herne UniversitätsklinikHerne, 44625, Germany
Withdrawn
Universitätsklinikum KölnKöln, 50937, Germany
Withdrawn
Universitätsklinikum Leipzig AöRLeipzig, 04103, Germany
Withdrawn
MarienhospitalStuttgart, 70199, Germany
Withdrawn
SRH Wald-Klinikum Gera gGmbHGera, 07548, Germany
Completed
Mayo Clinic - RochesterRochester, 55905, United States
Completed
Epworth HealthCareRichmond, 3122, Australia
Completed
Mid North Coast Cancer InstituteCoffs Harbour, 2450, Australia
Withdrawn
Klinikum der Universität München InnenstadtMünchen, 80336, Germany
Withdrawn
Evangelische Lungenklinik BerlinBerlin, 13125, Germany
Withdrawn
Stadt- und Landkreis Kliniken Heilbronn GmbHHeilbronn, 74078, Germany
Completed
Indiana University School of MedicineIndianapolis, 46202, United States
Completed
Northern Cancer InstituteSt Leonards, 2065, Australia
Completed
Flinders Medical CentreAdelaide, 5042, Australia
Completed
Cross Cancer InstituteEdmonton, T6G 1Z2, Canada
Completed
Princess Margaret Cancer Centre - UHNToronto, M5G 2M9, Canada
Completed
Sir Mortimer B. Davis Jewish General HospitalMontreal, H3T 1E2, Canada
Completed
Hôpital PontchaillouRENNES CEDEX, 35033, France
Completed
Centre Eugène Marquis - Rennes CedexRENNES CEDEX, 35062, France
Withdrawn
Universitätsklinikum Carl Gustav Carus DresdenDresden, 01307, Germany
Withdrawn
Erasmus Medisch CentrumROTTERDAM, 3075 EA, Netherlands
Completed
Nederlands Kanker InstituutAMSTERDAM, 1066 CX, Netherlands
Withdrawn
Thoraxklinik-Heidelberg gGmbHHeidelberg, 69126, Germany
Completed
Centre Léon BérardLYON CEDEX, 69008, France
Completed
Kantonsspital GraubündenChur, 7000, Switzerland
Completed
Ospedale Regionale BellinzonaBellinzona, 6500, Switzerland
Completed
Institut Gustave RoussyVILLEJUIF CEDEX, 94805, France
Completed
Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.Milano, 20089, Italy
Completed
A.O.U. di Bologna Policlinico S.Orsola MalpighiBologna, 40138, Italy
Completed
ASST Grande Ospedale Metropolitano NiguardaMilano, 20162, Italy
Completed
A.O.U. di Modena - PoliclinicoModena, 41124, Italy
Completed
Fondazione IRCCS Istituto Nazionale dei TumoriMilano, 20133, Italy
Completed
A.O.U.I. VeronaVerona, 37134, Italy
Withdrawn
Institut Paoli CalmettesMarseille Cedex 9, 13273, France
Completed
Hôpital de la MilétriePOITIERS cedex, 86021, France
Withdrawn
Klinikum der Stadt Köln gGmbH - Krankenhaus MerheimKöln, 51109, Germany
Completed
Centre Antoine LacassagneNICE CEDEX 2, 06102, France
Completed
Barbara Ann Karmanos Cancer InstituteFarmington Hills, 48334, United States
Completed
Stanford Health CareStanford, 94305, United States
Completed
Ochsner Medical Center - New OrleansNew Orleans, 70121, United States
Completed
University of Southern CaliforniaLos Angeles, 90033, United States
Completed
Severance Hospital, Yonsei University Health SystemSeoul, 03722, Korea, Republic Of
Completed
Washington University School of MedicineSt. Louis, 63110, United States
Completed
Asan Medical CenterSeoul, 05505, Korea, Republic Of
Completed
Asan Medical CenterSeoul, 05505, Korea, Republic Of
Completed
Samsung Medical CenterSeoul, 06351, Korea, Republic Of
Completed
Seoul National University HospitalSeoul, 03080, Korea, Republic Of
Completed
Guy’s HospitalLondon, SE1 9RT, United Kingdom
Withdrawn
Southampton General HospitalSouthampton, SO16 6YD, United Kingdom
Completed
Christie HospitalManchester, M20 4BX, United Kingdom
Completed
Royal Marsden NHS Trust (Surrey)Sutton, SM2 5PT, United Kingdom
Completed
Royal Marsden Hospital (London)London, SW3 6JJ, United Kingdom
Completed
Leicester Royal InfirmaryLeicester, LE1 5WW, United Kingdom
Withdrawn
Beatson West of Scotland Cancer CentreGlasgow, G12 0YN, United Kingdom
Completed
Belfast City HospitalBelfast, BT12 7AB, United Kingdom
Completed
Hospital Universitario Quirón de MadridPozuelo de Alarcón, 28223, Spain
Completed
Hospital del MarBarcelona, 08003, Spain
Completed
Hospital General Universitario Gregorio Marañón | OncologíaMadrid, 28007, Spain
Completed
Texas Oncology, PADallas, 75246, United States
Withdrawn
Mayo Clinic - JacksonvilleJacksonville, 32224, United States
Withdrawn
Institue Curie - Saint-CloudSAINT CLOUD, 92210, France
Withdrawn
Banner MD Anderson Cancer CenterGilbert, 85234, United States
Completed
McGill University Health CenterMontreal, H4A 3J1, Canada
Withdrawn
Institut Curie - Ulm - ParisPARIS, 75005, France
Completed
Maastricht UMCMAASTRICHT, 6229 HX, Netherlands

Primary Outcome

  • Number of patients in the safety lead-in (SLI) phase who completed Cycle 1 or had a DLT and were not replaced.
    During SLI, patients with cholangiocarcinoma received anetumab ravtansine in combination with cisplatin and patients with pancreatic adenocarcinoma received anetumab ravtansine in combination with gemcitabine. The highest dose of anetumab ravtansine that can be given so that not more than 1 out of 6 patients experiences a dose-limiting toxicity (DLT) during the DLT evaluation period were declared as the MTD for anetumab ravtansine in combination with cisplatin or with gemcitabine.
    date_rangeTime Frame:
    At least 3 weeks after the last patient starts treatment
    enhanced_encryption
    Safety Issue:
    Yes
  • Objective response (qualitative improvement from baseline) of anetumab ravtansine for monotherapy and combination therapy in mesothelin expressing advanced solid tumors
    A patient is a responder if the patient has a best response compared to baseline of complete response (CR) or partial response (PR) among all post-baseline tumor assessments, as determined per RECIST 1.1 criteria (ITMIG modified RECIST 1.1 criteria for thymic carcinoma)
    date_rangeTime Frame:
    Up to approximately 26 months after patient starts treatment
    enhanced_encryption
    Safety Issue:
    No
  • Durable disease control (lack of progression from baseline) of anetumab ravtansine in indications pancreatic and gastric cancer (co-primary endpoint)
    A patient experiences durable disease control if the patient has a tumor response compared to baseline of CR, PR or stable disease (SD) among the post-baseline tumor assessments made at least 180 days from first treatment, without prior disease progression
    date_rangeTime Frame:
    Up to approximately 26 months after patient starts treatment

Secondary Outcome

  • Number of serious and non-serious adverse events (AEs)
    Include treatment-emergent AEs, SAEs, treatment-related AEs, AEs of special interest, and deaths.
    date_rangeTime Frame:
    Approximately 26 months (Until 30 days after the last day of study treatment, or until later resolution of adverse events or determination by the investigator that the event will not improve)
    enhanced_encryption
    Safety Issue:
    Yes
  • Disease control rate (DCR)
    The DCR is defined as the number of patients with disease control divided by the number of treated patients.
    date_rangeTime Frame:
    Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
    enhanced_encryption
    Safety Issue:
    No
  • Duration of response (DOR)
    DOR is defined in responders as the time from documentation of tumor response (CR or PR) to earlier of disease progression or death
    date_rangeTime Frame:
    Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
    enhanced_encryption
    Safety Issue:
    No
  • Durable response rate (DRR)
    A durable responder is defined as a responder (CR or PR) with a duration of response per RECIST 1.1 criteria (ITMIG modified RECIST 1.1 criteria for thymic carcinoma) of 180 days or more. The DRR is the number of durable responders divided by the number of treated patients.
    date_rangeTime Frame:
    Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
    enhanced_encryption
    Safety Issue:
    No
  • Progression free survival (PFS)
    PFS is defined as time from start of treatment until disease progression according to RECIST 1.1 (ITMIG modified RECIST 1.1 criteria for thymic carcinoma) or death.
    date_rangeTime Frame:
    Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
    enhanced_encryption
    Safety Issue:
    No
  • Durable disease control rate (DDCR) of anetumab ravtansine in indications other than pancreatic and gastric cancer
    A patient experiences durable disease control if the patient has a tumor response of CR, PR or SD with CR, PR or SD assessed at least 180 days from first treatment, without prior progression.
    date_rangeTime Frame:
    Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]

Trial design

Phase 1b multi-indication study of anetumab ravtansine (BAY94-9343) in patients with mesothelin expressing advanced or recurrent malignancies
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
Open Label
Assignment
Parallel Assignment
Trial Arms
3

Additional Information

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