Clinical Trials /

Phase II Anetumab Ravtansine in Pre-treated Mesothelin-expressing Pancreatic Cancer

NCT03023722

Description:

The primary objective of this study is to: -Test the activity/response rate per RECIST 1.1 criteria of anetumab ravtansine in patients with advanced pancreatic cancer who stain for mesothelin expression The secondary objectives of this study are to: - Time to Progression (TTP) defined as time from study treatment to RECIST 1.1 progression, or death (others going off study will be censored) - Toxicity in pancreatic cancer patients (at 6.5 mg/kg dose)

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Anetumab Ravtansine in Pre-treated Mesothelin-expressing Pancreatic Cancer
  • Official Title: An Open-label, Phase II Study of Intravenous Anetumab Ravtansine (BAY 94-9343), an Anti-mesothelin Antibody Drug Conjugate, in Pretreated Mesothelin-expressing Advanced Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 1608018265
  • NCT ID: NCT03023722

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
anetumab ravtansineAll Subjects

Purpose

The primary objective of this study is to: -Test the activity/response rate per RECIST 1.1 criteria of anetumab ravtansine in patients with advanced pancreatic cancer who stain for mesothelin expression The secondary objectives of this study are to: - Time to Progression (TTP) defined as time from study treatment to RECIST 1.1 progression, or death (others going off study will be censored) - Toxicity in pancreatic cancer patients (at 6.5 mg/kg dose)

Detailed Description

      This is a non-randomized, open-label, multicenter, Phase II study to evaluate the efficacy
      and safety of intravenous anetumab ravtansine (BAY 94-9343), an anti-mesothelin antibody drug
      conjugate, in pretreated mesothelin-expressing advanced pancreatic cancer.

      At the time of the start of study treatment, the patients will have pretreated advanced
      pancreatic cancer that also overexpresses mesothelin as determined by immunohistochemistry
      (IHC).

      A maximum of 30 patients will be enrolled in a minimax, Simon 2-stage design with a single
      early stopping rule for lack of efficacy. The target population is those patients with
      pancreatic cancer who have failed an earlier treatment. All patients will be treated with an
      anti-mesothelin immuno-conjugate, in this single arm, non-randomized trial and all patients
      treated with at least one dose of Anetumab will be included. The endpoint is any response
      using the RECIST 1.1 criteria.
    

Trial Arms

NameTypeDescriptionInterventions
All SubjectsExperimentalPatients with advanced metastatic pancreatic cancer who have measurable disease
  • anetumab ravtansine

Eligibility Criteria

        Inclusion Criteria:

        Eligibility criteria for prescreening

          -  Patients with advanced metastatic pancreatic cancer who have measurable disease

          -  Must have had at least one and not more than two prior chemotherapy regimens for
             advanced disease (neoadjuvant chemotherapy would not be counted as a line of therapy).
             If prior radiation, measurable lesion outside radiation portal. ECOG performance
             status 0-1; Mesothelin positive. Must have normal organ function with LFTs <2.5 x ULN,
             no history of keratitis or corneal disease.

          -  Written informed consent for prescreening.

          -  Unresectable locally advanced or metastatic pancreatic cancer, confirmed by histology,
             and at least one but not more than two prior chemotherapy regimens with progression
             (neoadjuvant chemotherapy would not be counted as a line of therapy).

          -  Availability of archival or fresh tissue for testing of mesothelin expression level.

        Note: Archival tissue is preferred and fresh biopsy should only be obtained if no archival
        tissue is available and if in the investigator's judgement, there is no additional risk for
        the patient's safety. Patients with a sarcomatoid histology are not expected to have
        mesothelin overexpression and should not enter prescreening.

          -  Age ≥ 18 years.

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1

          -  Life expectancy of at least 3 months.

          -  No prior treatment with anetumab ravtansine (or any other mesothelin-based therapy)

        Eligibility criteria for full study

          -  Written informed consent for full study.

          -  Histological documentation of overexpressing mesothelin at the moderate (2+) or
             stronger (3+) level in at least 30% of tumor cells as determined by IHC.

          -  Unresectable locally advanced or metastatic pancreatic cancer

          -  At least one but not more than two prior chemotherapy regimens with progression
             (neoadjuvant chemotherapy would not be counted as a line of therapy).

          -  Patients must have at least 1 measurable lesion according to RECIST v 1.1

          -  ECOG PS of 0 or 1

          -  Life expectancy of at least 3 months.

          -  Adequate bone marrow, liver and renal function as assessed by the following laboratory
             requirements conducted within 7 days before starting study treatment:

          -  Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Documented Gilbert syndrome
             is allowed if total bilirubin is mildly elevated (< 6 mg/dL).

          -  ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their
             cancer).

          -  ALP limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer).

          -  Extent of baseline tumor burden will not interfere with causal assessment of
             treatment-emergent hepatotoxicity, at the investigator's discretion.

          -  Amylase and lipase ≤ 1.5 x ULN.

          -  Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of
             Diet in Renal Disease (MDRD) abbreviated formula (see Appendix 16.6).

          -  Adequate coagulation, as assessed by the following laboratory test results:

          -  International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN (CTCAE Grade
             ≤ 1).

          -  Partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN (CTCAE Grade ≤
             1).

        Note: Patients on stable dose of anti-coagulation therapy will be allowed to participate if
        they have no sign of bleeding or clotting and INR / PT and PTT / aPTT test results are
        compatible with the acceptable benefit-risk ratio at the investigator's discretion

          -  Platelet count ≥ 75,000/mm3 , without platelet transfusion within 3 weeks before the
             start of study treatment.

          -  Hemoglobin (Hb) ≥ 8 g/dL, without blood transfusion or erythropoietin within 6 weeks
             before the start of study treatment.

        Note: Patients receiving chronic low-dose erythropoietin for chronic renal failure are
        allowed provided no dose adjustment is undertaken within 6 weeks before signing consent for
        full study and until safety follow-up visit and provided that they fulfill conditions of
        eligibility criteria (see also exclusion criterion number 18).

          -  Absolute neutrophil count (ANC) ≥ 1000/mm3, without biologic response modifiers, such
             as G-CSF, within 6 weeks before the start of study treatment (see Section 8.1).

          -  Left ventricular ejection fraction (LVEF) ≥ 50% or the lower limit of normal (LLN)
             according to local institution ranges of normality

        Exclusion Criteria:

          -  Previous assignment to treatment during this study. Patients permanently withdrawn
             from study participation will not be allowed to re-enter the study.

          -  Previous (within 5 drug half-lives - if drug half-life in subjects is known - or 28
             days, whichever is shorter, before the start of study treatment) or concomitant
             participation in another clinical study with investigational medicinal product(s)
             (IMP[s]).

          -  Patients with corneal epitheliopathy or any eye disorder that may predispose the
             patients to this condition at the discretion of the ophthalmologist.

          -  Previous or concurrent cancer that is distinct in primary site or histology within 5
             years. Exceptions: curatively treated

          -  Cervical cancer in situ.

          -  Non-melanoma skin cancer.

          -  Superficial bladder tumors (Non-invasive tumor [Ta], Carcinoma in situ [Tis] and Tumor
             invades lamina propria [T1]).

          -  Major surgery, open biopsy or significant traumatic injury within 28 days before the
             start of study treatment.

          -  Pregnant or breast-feeding patients. Women of childbearing potential must have a serum
             pregnancy test performed a maximum of 7 days before the start of study treatment, and
             a negative result must be documented before the start of study treatment.

          -  Pre-existing cardiac conditions as outlined below:

          -  Congestive heart failure ≥ New York Heart Association (NYHA) class 2.

          -  Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
             months). Myocardial infarction less than 6 months before the start of study treatment.

          -  Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are
             permitted).

          -  Clinically significant uncontrolled hypertension (systolic blood pressure > 150 mmHg
             or diastolic pressure > 90 mmHg despite optimal medical management).

          -  Arterial thrombotic or embolic events such as cerebrovascular accident (including
             transient ischemic attacks), or venous pulmonary embolism within 6 months before the
             start of study treatment; venous thrombotic events such as deep vein thrombosis within
             3 months before the start of study treatment.

          -  Ongoing or active infection (bacterial, fungal, or viral) of NCI-CTCAE version 4.03
             Grade > 2.

          -  Known history of human immunodeficiency virus (HIV) infection.

          -  Known history of chronic hepatitis B or C.

          -  Patients with seizure disorder requiring medication.

          -  Symptomatic brain metastases or meningeal tumors or other uncontrolled metastases in
             the central nervous system (CNS) unless the patient

          -  Is > 6 months from definitive therapy,

          -  Has a negative imaging study within 4 weeks before study entry (ICF signature for full
             study) and

          -  Is clinically stable with respect to the tumor at the time of study entry.

          -  History of organ allograft, stem cells or bone marrow transplant.

          -  Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding
             event ≥ CTCAE Grade 3 within 4 weeks before the start of study treatment.

          -  Non-healing wound, ulcer, or bone fracture.

          -  Renal failure requiring peritoneal dialysis or hemodialysis.

          -  Known hypersensitivity to anetumab ravtansine, study drug classes or excipients in the
             formulation.

          -  Any illness or medical conditions that are unstable or could jeopardize the safety of
             the patient and his/her compliance in the study.

          -  Unresolved toxicity higher than NCI-CTCAE version 4.03 Grade 1 attributed to any prior
             therapy/procedure excluding anemia or neuropathy Grade 2 and alopecia of any Grade.

          -  Any prohibited prior or concomitant therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate as measured per RECIST 1.1 criteria
Time Frame:up to 3 years
Safety Issue:
Description:Primary efficacy will be assessed based on radiological tumor evaluation by contrast-enhanced computed tomography (CT) or contrast-enhanced magnetic resonance imaging (MRI) of chest/abdomen/pelvis.

Secondary Outcome Measures

Measure:Time to Progression
Time Frame:up to 3.5 years
Safety Issue:
Description:Time to Progression (TTP) defined as time from study treatment to RECIST progression, or death (others going off study will be censored).
Measure:Toxicity
Time Frame:up to 3 years
Safety Issue:
Description:Toxicity of Anetumab ravtansine assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Howard Hochster

Last Updated

August 9, 2017