Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin Expressing Advanced Solid Tumors
ARCS-Multi
2 other identifiers
interventional
173
12 countries
72
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2017
Longer than P75 for phase_1
72 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 30, 2017
CompletedFirst Posted
Study publicly available on registry
April 5, 2017
CompletedStudy Start
First participant enrolled
May 26, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 16, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 26, 2021
CompletedJune 30, 2022
June 1, 2022
3.3 years
March 30, 2017
June 28, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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.
At least 3 weeks after the last patient starts treatment
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)
Up to approximately 26 months after patient starts treatment
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
Up to approximately 26 months after patient starts treatment
Secondary Outcomes (6)
Number of serious and non-serious adverse events (AEs)
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)
Disease control rate (DCR)
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]
Duration of response (DOR)
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]
Durable response rate (DRR)
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]
Progression free survival (PFS)
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]
- +1 more secondary outcomes
Study Arms (3)
Cholangiocarcinoma
EXPERIMENTALSafety 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.
Adenocarcinoma of the pancreas
EXPERIMENTALSafety 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
Other solid tumors
EXPERIMENTAL(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
Interventions
Cisplatin 25 mg/m2 IV administered on day 1 and day 8 of 21 day cycle, for up to maximum 6 cycles
Gemcitabine 1000 mg/m2 IV administered on days 1 and 8 of a 21-day cycle
Anetumab ravtansine 6.5mg/kg IV in monotherapy indications. For combination indications, the MTD determined in safety lead in phase will be administered
Eligibility Criteria
You may qualify if:
- Availability of tumor tissue for mesothelin expression testing and for further biomarker analysis
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
- ImmunoGen, Inc.collaborator
- MorphoSys AGcollaborator
Study Sites (72)
Mayo Clinic Hospital
Phoenix, Arizona, 85054-4502, United States
University of Southern California
Los Angeles, California, 90033, United States
Stanford Health Care
Stanford, California, 94305, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
Ochsner Medical Center - New Orleans
New Orleans, Louisiana, 70121, United States
National Cancer Institute - Maryland
Bethesda, Maryland, 20892, United States
Barbara Ann Karmanos Cancer Institute
Farmington Hills, Michigan, 48334, United States
Mayo Clinic - Rochester
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Texas Oncology, PA
Dallas, Texas, 75246, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Blacktown Cancer & Haematology Centre
Blacktown, New South Wales, 2148, Australia
Mid North Coast Cancer Institute
Coffs Harbour, New South Wales, 2450, Australia
Kinghorn Cancer Centre
Darlinghurst, New South Wales, 2010, Australia
Northern Cancer Institute
St Leonards, New South Wales, 2065, Australia
Flinders Medical Centre
Adelaide, South Australia, 5042, Australia
Epworth HealthCare
Richmond, Victoria, 3122, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
St John of God Healthcare
Subiaco, Western Australia, 6008, Australia
Hôpital Erasme/Erasmus Ziekenhuis
Bruxelles - Brussel, 1070, Belgium
UZ Antwerpen
Edegem, 2650, Belgium
UZ Leuven Gasthuisberg
Leuven, 3000, Belgium
CHU de Liège
Liège, 4000, Belgium
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
Princess Margaret Cancer Centre - UHN
Toronto, Ontario, M5G 2M9, Canada
Sir Mortimer B. Davis Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
McGill University Health Center
Montreal, Quebec, H4A 3J1, Canada
Hopital Jean Minjoz
Besançon, 25030, France
Hôpital Henri Mondor
Créteil, 94010, France
Centre Oscar Lambret - Lille
Lille, 59020, France
Centre Léon Bérard
Lyon, 69008, France
C.H.U. Timone
Marseille, 13385, France
Centre René Gauducheau
Nantes, 44805, France
Centre Antoine Lacassagne
Nice, 06102, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495, France
Hôpital de la Milétrie
Poitiers, 86021, France
Hôpital Pontchaillou
Rennes, 35033, France
Centre Eugène Marquis - Rennes Cedex
Rennes, 35062, France
Institut Gustave Roussy
Villejuif, 94805, France
A.O.U. di Bologna Policlinico S.Orsola Malpighi
Bologna, Emilia-Romagna, 40138, Italy
A.O.U. di Modena - Policlinico
Modena, Emilia-Romagna, 41124, Italy
Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
Milan, Lombardy, 20089, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, 20133, Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, Lombardy, 20162, Italy
A.O.U.I. Verona
Verona, Veneto, 37134, Italy
Nederlands Kanker Instituut
Amsterdam, 1066 CX, Netherlands
Maastricht UMC
Maastricht, 6229 HX, Netherlands
National University Hospital
Singapore, 119228, Singapore
National Cancer Center Singapore
Singapore, 169610, Singapore
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hospital Universitario Quirón de Madrid
Pozuelo de Alarcón, Madrid, 28223, Spain
Hospital del Mar
Barcelona, 08003, Spain
Ciutat Sanitària i Universitaria de la Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clínic i Provincial de Barcelona
Barcelona, 08036, Spain
Hospital General Universitario Gregorio Marañón | Oncología
Madrid, 28007, Spain
Hospital Ramón y Cajal | Oncología
Madrid, 28034, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Centro Integral Oncológico Clara Campal
Madrid, 28050, Spain
Hospital Virgen de la Victoria
Málaga, 29010, Spain
Ospedale Regionale Bellinzona
Bellinzona, Canton Ticino, 6500, Switzerland
Kantonsspital Graubünden
Chur, Kanton Graubünden, 7000, Switzerland
Leicester Royal Infirmary
Leicester, Leicestershire, LE1 5WW, United Kingdom
Belfast City Hospital
Belfast, North Ireland, BT12 7AB, United Kingdom
Royal Marsden NHS Trust (Surrey)
Sutton, Surrey, SM2 5PT, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
Royal Marsden Hospital (London)
London, SW3 6JJ, United Kingdom
Christie Hospital
Manchester, M20 4BX, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 30, 2017
First Posted
April 5, 2017
Study Start
May 26, 2017
Primary Completion
September 16, 2020
Study Completion
July 26, 2021
Last Updated
June 30, 2022
Record last verified: 2022-06
Data Sharing
- IPD Sharing
- Will not share
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.