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Trial record 1 of 1 for:    NCT03102320
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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

Tracking Information
First Submitted Date  ICMJE March 30, 2017
First Posted Date  ICMJE April 5, 2017
Last Update Posted Date August 13, 2019
Actual Study Start Date  ICMJE May 26, 2017
Estimated Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2018)
  • 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
  • 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)
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: March 30, 2017)
  • 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
  • Objective response rate (ORR) of anetumab ravtansine for monotherapy and combination therapy in mesothelin expressing advanced solid tumors [ Time Frame: 18 weeks after last patient starts treatment ]
    A patient is a responder if the patient has a tumor response of CR or PR, as determined per RECIST 1.1 criteria (ITMIG modified RECIST 1.1 criteria for thymic carcinoma). In the Phase 1b portion of this study, the ORR is defined separately in each indication and mesothelin expression cohort, as the number of responders divided by the number of treated patients in the indication and mesothelin expression cohort
Change History Complete list of historical versions of study NCT03102320 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2018)
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2017)
  • Number of serious and non-serious adverse events (AEs) [ Time Frame: 18 weeks after last patient starts treatment ]
    Include treatment-emergent AEs, SAEs, treatment-related AEs, AEs of special interest, and deaths.
  • Disease control rate (DCR) [ Time Frame: 18 weeks after last patient starts treatment ]
    The DCR is defined as the number of patients with disease control divided by the number of treated patients.
  • Duration of response (DOR) [ Time Frame: Approximately 24 months after last patient starts treatment ]
    DOR is defined in responders as the time from documentation of tumor response (CR or PR) to earlier of disease progression or death
  • Durable response rate (DRR) [ Time Frame: Approximately 24 months after last patient starts treatment ]
    The DRR is the number of durable responders divided by the number of treated patients.
  • Progression free survival (PFS) [ Time Frame: Approximately 24 months after last patient starts treatment ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin Expressing Advanced Solid Tumors
Official Title  ICMJE Phase 1b Multi-indication Study of Anetumab Ravtansine (BAY94-9343) in Patients With Mesothelin Expressing Advanced or Recurrent Malignancies
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • 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: 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
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Cisplatin
    • Drug: Anetumab ravtansine (BAY94-9343)
  • 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
    Interventions:
    • Drug: Gemcitabine
    • Drug: Anetumab ravtansine (BAY94-9343)
  • 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
    Intervention: Drug: Anetumab ravtansine (BAY94-9343)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 30, 2017)
348
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 28, 2021
Estimated Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Italy,   Korea, Republic of,   Netherlands,   Singapore,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03102320
Other Study ID Numbers  ICMJE 15834
2016-004002-33 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE
  • ImmunoGen, Inc.
  • MorphoSys AG
Investigators  ICMJE Not Provided
PRS Account Bayer
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP