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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03102320




Registration number
NCT03102320
Ethics application status
Date submitted
30/03/2017
Date registered
5/04/2017
Date last updated
30/06/2022

Titles & IDs
Public title
Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin Expressing Advanced Solid Tumors
Scientific title
Phase 1b Multi-indication Study of Anetumab Ravtansine (BAY94-9343) in Patients With Mesothelin Expressing Advanced or Recurrent Malignancies
Secondary ID [1] 0 0
2016-004002-33
Secondary ID [2] 0 0
15834
Universal Trial Number (UTN)
Trial acronym
ARCS-Multi
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Anetumab ravtansine (BAY94-9343)

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.

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

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


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

Treatment: Drugs: Gemcitabine
Gemcitabine 1000 mg/m2 IV administered on days 1 and 8 of a 21-day cycle

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of patients in the safety lead-in (SLI) phase who completed Cycle 1 or had a DLT and were not replaced.
Timepoint [1] 0 0
At least 3 weeks after the last patient starts treatment
Primary outcome [2] 0 0
Objective response (qualitative improvement from baseline) of anetumab ravtansine for monotherapy and combination therapy in mesothelin expressing advanced solid tumors
Timepoint [2] 0 0
Up to approximately 26 months after patient starts treatment
Primary outcome [3] 0 0
Durable disease control (lack of progression from baseline) of anetumab ravtansine in indications pancreatic and gastric cancer (co-primary endpoint)
Timepoint [3] 0 0
Up to approximately 26 months after patient starts treatment
Secondary outcome [1] 0 0
Number of serious and non-serious adverse events (AEs)
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Disease control rate (DCR)
Timepoint [2] 0 0
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]
Secondary outcome [3] 0 0
Duration of response (DOR)
Timepoint [3] 0 0
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]
Secondary outcome [4] 0 0
Durable response rate (DRR)
Timepoint [4] 0 0
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]
Secondary outcome [5] 0 0
Progression free survival (PFS)
Timepoint [5] 0 0
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]
Secondary outcome [6] 0 0
Durable disease control rate (DDCR) of anetumab ravtansine in indications other than pancreatic and gastric cancer
Timepoint [6] 0 0
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]

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/07/2021
Sample size
Target
Accrual to date
Final
173
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Cancer & Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
Mid North Coast Cancer Institute - Coffs Harbour
Recruitment hospital [3] 0 0
Kinghorn Cancer Centre - Darlinghurst
Recruitment hospital [4] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [5] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [6] 0 0
Epworth HealthCare - Richmond
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [8] 0 0
St John of God Healthcare - Subiaco
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
5042 - Adelaide
Recruitment postcode(s) [6] 0 0
3122 - Richmond
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment postcode(s) [8] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Belgium
State/province [12] 0 0
Bruxelles - Brussel
Country [13] 0 0
Belgium
State/province [13] 0 0
Edegem
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Belgium
State/province [15] 0 0
Liege
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
France
State/province [19] 0 0
Besancon
Country [20] 0 0
France
State/province [20] 0 0
Creteil
Country [21] 0 0
France
State/province [21] 0 0
Lille Cedex
Country [22] 0 0
France
State/province [22] 0 0
Lyon Cedex
Country [23] 0 0
France
State/province [23] 0 0
Marseille
Country [24] 0 0
France
State/province [24] 0 0
Nantes
Country [25] 0 0
France
State/province [25] 0 0
Nice Cedex 2
Country [26] 0 0
France
State/province [26] 0 0
Pierre Benite
Country [27] 0 0
France
State/province [27] 0 0
POITIERS cedex
Country [28] 0 0
France
State/province [28] 0 0
Rennes Cedex
Country [29] 0 0
France
State/province [29] 0 0
Villejuif Cedex
Country [30] 0 0
Italy
State/province [30] 0 0
Emilia-Romagna
Country [31] 0 0
Italy
State/province [31] 0 0
Lombardia
Country [32] 0 0
Italy
State/province [32] 0 0
Veneto
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Seoul
Country [34] 0 0
Netherlands
State/province [34] 0 0
Amsterdam
Country [35] 0 0
Netherlands
State/province [35] 0 0
Maastricht
Country [36] 0 0
Singapore
State/province [36] 0 0
Singapore
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Málaga
Country [40] 0 0
Switzerland
State/province [40] 0 0
Graubünden
Country [41] 0 0
Switzerland
State/province [41] 0 0
Ticino
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Leicestershire
Country [43] 0 0
United Kingdom
State/province [43] 0 0
North Ireland
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Surrey
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
ImmunoGen, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
MorphoSys AG
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT03102320
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03102320