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Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin Expressing Advanced Solid Tumors (ARCS-Multi)

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ClinicalTrials.gov Identifier: NCT03102320
Recruitment Status : Recruiting
First Posted : April 5, 2017
Last Update Posted : August 13, 2019
Sponsor:
Collaborators:
ImmunoGen, Inc.
MorphoSys AG
Information provided by (Responsible Party):
Bayer

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Neoplasms Drug: Cisplatin Drug: Gemcitabine Drug: Anetumab ravtansine (BAY94-9343) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 348 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Multi-indication Study of Anetumab Ravtansine (BAY94-9343) in Patients With Mesothelin Expressing Advanced or Recurrent Malignancies
Actual Study Start Date : May 26, 2017
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : July 28, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cholangiocarcinoma

Safety lead-in phase will determine the MTD of anetumab ravtansine administered in combination with cisplatin. Please note the study is no longer recruiting for the cholangiocarcinoma safety lead-in phase.

During the main study phase anetumab ravtansine will be administered at the determined MTD in combination with cisplatin. Please note the main study phase for cholangiocarcinoma will no longer be going ahead.

Drug: Cisplatin
Cisplatin 25 mg/m2 IV administered on day 1 and day 8 of 21 day cycle, for up to maximum 6 cycles

Drug: Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine 6.5mg/kg IV in monotherapy indications. For combination indications, the MTD determined in safety lead in phase will be administered

Experimental: Adenocarcinoma of the pancreas
Safety lead-in phase will determine the MTD of anetumab ravtansine administered in combination with gemcitabine During the main study phase, anetumab ravtansine will be administered at the determined MTD in combination with gemcitabine
Drug: Gemcitabine
Gemcitabine 1000 mg/m2 IV administered on days 1 and 8 of a 21-day cycle

Drug: Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine 6.5mg/kg IV in monotherapy indications. For combination indications, the MTD determined in safety lead in phase will be administered

Experimental: Other solid tumors
(Non-small cell adenocarcinoma of the lung (NSCLC adenocarcinoma), Adenocarcinoma of the breast - triple negative (TNBC), Gastric adenocarcinoma including gastroesophageal junction (GEJ Cancer, Thymic carcinoma) During the main study phase, anetumab ravtansine will be administered at dose of 6.5 mg/kg in solid tumors
Drug: Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine 6.5mg/kg IV in monotherapy indications. For combination indications, the MTD determined in safety lead in phase will be administered




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of anetumab ravtansine in combination with cisplatin and in combination with gemcitabine in patients with mesothelin-expressing cholangiocarcinoma and pancreatic adenocarcinoma [ Time Frame: At least 3 weeks after the last patient starts treatment ]
    The highest dose of anetumab ravtansine that can be given so that not more than 1 out of 6 patients experiences a DLT (during the DLT evaluation period) will be declared as the MTD for anetumab ravtansine in combination with cisplatin or with gemcitabine

  2. Objective response (qualitative improvement from baseline) of anetumab ravtansine for monotherapy and combination therapy in mesothelin expressing advanced solid tumors [ Time Frame: Up to approximately 26 months after patient starts treatment ]
    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)

  3. Durable disease control (lack of progression from baseline) of anetumab ravtansine in indications pancreatic and gastric cancer (co-primary endpoint) [ Time Frame: Up to approximately 26 months after patient starts treatment ]
    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


Secondary Outcome Measures :
  1. Number of serious and non-serious adverse events (AEs) [ Time 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) ]
    Include treatment-emergent AEs, SAEs, treatment-related AEs, AEs of special interest, and deaths.

  2. Disease control rate (DCR) [ Time 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] ]
    The DCR is defined as the number of patients with disease control divided by the number of treated patients.

  3. Duration of response (DOR) [ Time 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] ]
    DOR is defined in responders as the time from documentation of tumor response (CR or PR) to earlier of disease progression or death

  4. Durable response rate (DRR) [ Time 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] ]
    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.

  5. Progression free survival (PFS) [ Time 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] ]
    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.

  6. Durable disease control rate (DDCR) of anetumab ravtansine in indications other than pancreatic and gastric cancer [ Time 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] ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03102320


Contacts
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Contact: Bayer Clinical Trials Contact (+) 1-888-8422937 clinical-trials-contact@bayer.com
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937

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Locations
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United States, Arizona
Banner MD Anderson Cancer Center Withdrawn
Gilbert, Arizona, United States, 85234
Mayo Clinic Hospital Recruiting
Phoenix, Arizona, United States, 85054-4502
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Stanford Health Care Recruiting
Stanford, California, United States, 94305
United States, Connecticut
Yale Cancer Center Withdrawn
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
United States, Florida
Mayo Clinic - Jacksonville Withdrawn
Jacksonville, Florida, United States, 32224
United States, Indiana
Indiana University School of Medicine Recruiting
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Ochsner Medical Center - New Orleans Completed
New Orleans, Louisiana, United States, 70121
United States, Maryland
National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892
United States, Michigan
University of Michigan Health System Withdrawn
Ann Arbor, Michigan, United States, 48109-0330
Barbara Ann Karmanos Cancer Institute Recruiting
Farmington Hills, Michigan, United States, 48334
United States, Minnesota
Mayo Clinic - Rochester Recruiting
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Oncology, PA Recruiting
Dallas, Texas, United States, 75246
University of Texas MD Anderson Cancer Center Completed
Houston, Texas, United States, 77030
Australia, New South Wales
Blacktown Cancer & Haematology Centre Recruiting
Blacktown, New South Wales, Australia, 2148
Mid North Coast Cancer Institute Recruiting
Coffs Harbour, New South Wales, Australia, 2450
Kinghorn Cancer Centre Recruiting
Darlinghurst, New South Wales, Australia, 2010
Northern Cancer Institute Recruiting
St Leonards, New South Wales, Australia, 2065
Australia, South Australia
Flinders Medical Centre Recruiting
Adelaide, South Australia, Australia, 5042
Australia, Victoria
Epworth HealthCare Recruiting
Richmond, Victoria, Australia, 3122
Australia, Western Australia
Sir Charles Gairdner Hospital Recruiting
Nedlands, Western Australia, Australia, 6009
St John of God Healthcare Recruiting
Subiaco, Western Australia, Australia, 6008
St John of God Healthcare Completed
Subiaco, Western Australia, Australia, 6008
Belgium
GZA Ziekenhuizen Withdrawn
Wilrijk, Antwerpen, Belgium, 2610
Hôpital Erasme/Erasmus Ziekenhuis Recruiting
Bruxelles - Brussel, Belgium, 1070
UZ Antwerpen Recruiting
Edegem, Belgium, 2650
UZ Leuven Gasthuisberg Recruiting
Leuven, Belgium, 3000
CHU de Liège Recruiting
Liege, Belgium, 4000
Canada, Alberta
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Sir Mortimer B. Davis Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
McGill University Health Center Recruiting
Montreal, Quebec, Canada, H4A 3J1
France
Hopital Jean Minjoz Recruiting
Besancon, France, 25030
Hôpital Henri Mondor Completed
Creteil, France, 94010
Centre Oscar Lambret - Lille Recruiting
Lille Cedex, France, 59020
Centre Léon Bérard Recruiting
Lyon Cedex, France, 69008
Institut Paoli Calmettes Withdrawn
Marseille Cedex 9, France, 13273
C.H.U. Timone Recruiting
Marseille, France, 13385
Centre René Gauducheau Recruiting
Nantes, France, 44805
Centre Antoine Lacassagne Recruiting
Nice Cedex 2, France, 06102
Institut Curie - Ulm - Paris Withdrawn
Paris, France, 75005
Centre Hospitalier Lyon Sud Recruiting
Pierre Benite, France, 69310
Hôpital de la Milétrie Recruiting
POITIERS cedex, France, 86021
Hôpital Pontchaillou Recruiting
Rennes Cedex, France, 35033
Centre Eugène Marquis - Rennes Cedex Recruiting
Rennes Cedex, France, 35062
Institue Curie - Centre René Huguenin Withdrawn
Saint Cloud, France, 92210
Institut Gustave Roussy Recruiting
Villejuif Cedex, France, 94805
Germany
Thoraxklinik-Heidelberg gGmbH Withdrawn
Heidelberg, Baden-Württemberg, Germany, 69126
Stadt- und Landkreis Kliniken Heilbronn GmbH Withdrawn
Heilbronn, Baden-Württemberg, Germany, 74078
Marienhospital Withdrawn
Stuttgart, Baden-Württemberg, Germany, 70199
Klinikum der Universität München Innenstadt Withdrawn
München, Bayern, Germany, 80336
Städt. Klinikum München Withdrawn
München, Bayern, Germany, 81737
Kliniken Nord und Süd Withdrawn
Nürnberg, Bayern, Germany, 90419
Universitätsklinikum Essen Withdrawn
Essen, Nordrhein-Westfalen, Germany, 45147
Marienhospital Herne Universitätsklinik Withdrawn
Herne, Nordrhein-Westfalen, Germany, 44625
Universitätsklinikum Köln Withdrawn
Köln, Nordrhein-Westfalen, Germany, 50937
Kliniken der Stadt Köln - Städt. Krankenhaus Köln-Merheim Withdrawn
Köln, Nordrhein-Westfalen, Germany, 51109
Universitätsklinikum Carl Gustav Carus Dresden Withdrawn
Dresden, Sachsen, Germany, 01307
Universitätsklinikum Leipzig AöR Withdrawn
Leipzig, Sachsen, Germany, 04103
SRH Wald-Klinikum Gera gGmbH Withdrawn
Gera, Thüringen, Germany, 07548
Evangelische Lungenklinik Berlin Withdrawn
Berlin, Germany, 13125
Italy
A.O.U. di Bologna Policlinico S.Orsola Malpighi Recruiting
Bologna, Emilia-Romagna, Italy, 40138
A.O.U. di Modena - Policlinico Recruiting
Modena, Emilia-Romagna, Italy, 41124
IRCCS Istituto Clinico Humanitas (ICH) Recruiting
Milano, Lombardia, Italy, 20089
Fondazione IRCCS Istituto Nazionale dei Tumori Recruiting
Milano, Lombardia, Italy, 20133
ASST Grande Ospedale Metropolitano Niguarda Recruiting
Milano, Lombardia, Italy, 20162
A.O.U. Integrata Verona Recruiting
Verona, Veneto, Italy, 37134
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Yonsei University College of Medicine Recruiting
Seoul, Korea, Republic of, 120-752
Netherlands
Nederlands Kanker Instituut Recruiting
Amsterdam, Netherlands, 1066 CX
Maastricht UMC Recruiting
Maastricht, Netherlands, 6229 HX
Erasmus Medisch Centrum Withdrawn
Rotterdam, Netherlands, 3075 EA
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119228
National Cancer Center Recruiting
Singapore, Singapore, 169610
Spain
Institut Català d'Oncologia Hospitalet Withdrawn
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital del Mar Recruiting
Barcelona, Catalunya, Spain, 08003
Hospital Universitario Quirón de Madrid Recruiting
Pozuelo de Alarcón, Madrid, Spain, 28223
Ciutat Sanitària i Universitaria de la Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Hospital Clínic i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Hospital Ramón y Cajal Recruiting
Madrid, Spain, 28034
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Hospital General Universitario Gregorio Marañón Recruiting
Madrid, Spain, 28046
Centro Integral Oncológico Clara Campal Recruiting
Madrid, Spain, 28050
Hospital Virgen de la Victoria Recruiting
Málaga, Spain, 29010
Switzerland
Kantonsspital Graubünden Recruiting
Chur, Graubünden, Switzerland, 7000
Ospedale Regionale Bellinzona Recruiting
Bellinzona, Ticino, Switzerland, 6500
United Kingdom
Leicester Royal Infirmary Recruiting
Leicester, Leicestershire, United Kingdom, LE1 5WW
Belfast City Hospital Recruiting
Belfast, North Ireland, United Kingdom, BT12 7AB
Royal Marsden NHS Trust (Surrey) Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Beatson West of Scotland Cancer Centre Withdrawn
Glasgow, United Kingdom, G12 0YN
Guy's Hospital Recruiting
London, United Kingdom, SE1 9RT
Royal Marsden Hospital (London) Recruiting
London, United Kingdom, SW3 6JJ
Christie Hospital Recruiting
Manchester, United Kingdom, M20 4BX
Southampton General Hospital Withdrawn
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Bayer
ImmunoGen, Inc.
MorphoSys AG

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03102320     History of Changes
Other Study ID Numbers: 15834
2016-004002-33 ( EudraCT Number )
First Posted: April 5, 2017    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
cholangiocarcinoma
pancreatic cancer
triple-negative breast cancer
non-small cell lung cancer
thymic carcinoma
gastric including gastroesophageal junction cancer

Additional relevant MeSH terms:
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Cisplatin
Gemcitabine
Maytansine
Immunoconjugates
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators