check_circleStudy Completed

Medical Oncology

Bayer Identifier:

17631

ClinicalTrials.gov Identifier:

NCT02639091

EudraCT Number:

2016-003988-18

EU CT Number:

Not Available
Phase Ib study of anetumab ravtansine in combination with pemetrexed and cisplatin in mesothelin-expressing solid tumors

Trial purpose

Determine the safety, tolerability and maximum tolerated dose of anetumab ravtansine (BAY 94-9343) in combination with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 in subjects with mesothelin-expressing predominantly epithelial mesothelioma or nonsquamous non-small-cell lung cancer.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - Subjects may be male or female, and must be aged =/>18 years on the date of signing the informed consent form.
    - Subjects must have histologically confirmed, unresectable, locally advanced or metastatic pleural or peritoneal predominantly (>50% of
    tumor component) epithelial mesothelioma or nonsquamous non-small-cell lung cancer (NSCLC). Both chemotherapy-naive and previously treated subjects will be eligible; however, newly diagnosed NSCLC subjects
    eligible for FDA-approved therapies should have
    received the same before enrollment (e.g. subjects with epidermal growth factor receptor [EGFR]-mutated and anaplastic lymphoma kinase
    [ALK]-translocated NSCLC should have received FDA-approved targeted therapies).
    - Subjects must have at least 1 measurable or evaluable tumor lesion according to RECIST 1.1 (for nonsquamous NSCLC) or mRECIST (for epithelial pleural mesothelioma). Subjects with resected primary tumors who have documented metastases are eligible.
    - Subjects must have a life expectancy of at least 12 weeks.
    - Subjects must have ECOG (Eastern Cooperative Oncology Group performance Status of 0 or 1
    - Subjects must have adequate bone marrow, liver, kidney, and coagulation functions.
  • - Subjects who have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, or any previous cancer curatively treated >3 years before the start of study Treatment.
    - Subjects who have a history or current evidence of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE (Common Terminology
    Criteria for Adverse Events) Grade ≥2 within 4 weeks before the start of study Treatment.
    - Subjects who have new or progressive brain or meningeal or spinal metastases.
    - Subjects who have a history or current evidence of uncontrolled cardiovascular disease i.e. NYHA (New York Heart Association) Class III or IV.
    - Subjects who have a history or current evidence of uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at screening despite optimal
    medical management.
    - Subjects who have a history or current evidence of malignant biliary obstruction requiring biliary stent.
    - Subjects who have had solid organ or bone marrow Transplantation.
    - Subjects who have a history of hypersensitivity to any of the study drugs or their excipients, or a history of severe hypersensitivity to any other Antigen.
    - Subjects who have a history of human immunodeficiency virus (HIV) infection or subjects who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
    - Subjects who have an active clinically serious infection of CTCAE Grade ≥2 or non-healing wound unrelated to the primary Tumor.
    - Subjects who have received systemic cancer therapy, radiotherapy, investigational drug treatment outside of this study within 4 weeks before the start of study treatment, granulocyte colony stimulating factors, (G-CSF) or granulocyte macrophage-stimulating factors (GM-CSF), erythropoietin-stimulating agents within 3 weeks before the start of general screening, drugs with known renal toxicity and strong cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers within 2 weeks before the treatment.
    - Subjects who have started oral or parenteral anticoagulation therapy within 2 weeks before the start of anetumab ravtansine until end of treatment visit.

Trial summary

Enrollment Goal
36
Trial Dates
February 2016 - October 2019
Phase
Phase 1
Could I Receive a placebo
No
Products
Anetumab ravtansine (BAY94-9343)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Bethesda, 20892, United States
Completed
Chicago, 60637, United States
Withdrawn
Houston, 77030, United States
Completed
Charleston, 29425, United States
Completed
Detroit, 48202, United States
Withdrawn
New Orleans, 70121, United States
Completed
Milano, 20133, Italy
Completed
Milano, 20089, Italy
Withdrawn
Parma, 43126, Italy
Withdrawn
Siena, 53100, Italy

Primary Outcome

  • Maximum tolerated dose (MTD)
    MTD is defined as the highest dose of oral anetumab ravtansine (BAY 94-9343) administered in combination with IV pemetrexed and cisplatin that can be given such that not more than 1 of 6 subjects at a given dose level experience a DLT (dose-limiting toxicity).
    date_rangeTime Frame:
    Up to 2 years
    enhanced_encryption
    Safety Issue:
    Yes
  • Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability
    date_rangeTime Frame:
    Up to 2 years
    enhanced_encryption
    Safety Issue:
    Yes

Secondary Outcome

  • Plasma concentrations of anetumab ravtansine (BAY 94-9343), pemetrexed and cisplatin
    C (treatment cycle), D (day); Each cycle is defined as a period of 21 days
    date_rangeTime Frame:
    - BAY 94-9343: C1D1,D2,D3,D8,D15, C2D1, C3D1,D2,D3,D8,D15, C4D1, C6D1 and subsequent cycles every 3rd cycle up to 2 years or until discontinuation of study treatment, whichever comes first - Pemetrexed: C1D1, D2, D3 - Cisplatin: C1D1, D2, D3
    enhanced_encryption
    Safety Issue:
    No
  • Tumor response evaluation following mRECIST criteria to determine the number of patients with CR, PR, SD or PD
    CR (complete response); PR (partial response); SD (stable disease); PD (progressive disease); Each cycle is defined as a period of 21 days
    date_rangeTime Frame:
    Baseline, every 8 weeks up to cycle 12; then every 12 weeks from cycle 13 up to 2 years, or until discontinuation of study treatment, whichever comes first
    enhanced_encryption
    Safety Issue:
    No
  • Number of patients with a positive titer of anti-drug antibodies
    Each cycle is defined as a period of 21 days
    date_rangeTime Frame:
    Day1 of C1, C3, C6 and subsequent cycles every 3rd cycle up to 2 years or until discontinuation of study treatment, whichever comes first
    enhanced_encryption
    Safety Issue:
    No

Trial design

An open label Phase Ib dose escalation study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and maximum tolerated dose of anetumab ravtansine in combination with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 in subjects with mesothelin-expressing predominantly epithelial mesothelioma or nonsquamous non-small-cell lung cancer
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
1

Additional Information

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