Clinical Trials /

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

NCT03102320

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03102320

Trial Eligibility

Document

Title

  • Brief Title: Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin Expressing Advanced Solid Tumors
  • Official Title: Phase 1b Multi-indication Study of Anetumab Ravtansine (BAY94-9343) in Patients With Mesothelin Expressing Advanced or Recurrent Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 15834
  • SECONDARY ID: 2016-004002-33
  • NCT ID: NCT03102320

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
CisplatinCholangiocarcinoma
GemcitabineAdenocarcinoma of the pancreas
Anetumab ravtansine (BAY94-9343)Adenocarcinoma of the pancreas

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.

Trial Arms

NameTypeDescriptionInterventions
CholangiocarcinomaExperimentalSafety 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.
  • Cisplatin
  • Anetumab ravtansine (BAY94-9343)
Adenocarcinoma of the pancreasExperimentalSafety 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
  • Gemcitabine
  • Anetumab ravtansine (BAY94-9343)
Other solid tumorsExperimental(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
  • Anetumab ravtansine (BAY94-9343)

Eligibility 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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:Include treatment-emergent AEs, SAEs, treatment-related AEs, AEs of special interest, and deaths.
Measure: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]
Safety Issue:
Description:The DCR is defined as the number of patients with disease control divided by the number of treated patients.
Measure: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]
Safety Issue:
Description:DOR is defined in responders as the time from documentation of tumor response (CR or PR) to earlier of disease progression or death
Measure: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]
Safety Issue:
Description: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.
Measure: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]
Safety Issue:
Description: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.
Measure: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]
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Bayer

Trial Keywords

  • cholangiocarcinoma
  • pancreatic cancer
  • triple-negative breast cancer
  • non-small cell lung cancer
  • thymic carcinoma
  • gastric including gastroesophageal junction cancer

Last Updated

August 6, 2021