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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03023722
Recruitment Status : Completed
First Posted : January 18, 2017
Results First Posted : January 22, 2021
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Yale University

Brief Summary:

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)

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: anetumab ravtansine Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 11, 2017
Actual Primary Completion Date : August 6, 2019
Actual Study Completion Date : December 11, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: All Subjects
Patients with advanced metastatic pancreatic cancer who have measurable disease
Drug: anetumab ravtansine
Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle




Primary Outcome Measures :
  1. Response Rate as Measured Per RECIST 1.1 Criteria [ Time Frame: From start of treatment until disease progression or death (up to 3 years). ]
    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. Contrast enhanced RECIST 1.1 scan will be done at Prescreening. Said pre-screen scan will be the baseline measure. RECIST 1.1 Scans will be done every 6 weeks for the first 6 months after the start of treatment, or more frequently if clinically indicated, every 9 weeks until the end of year 2 and every 12 weeks thereafter until disease progression or end of study, whichever comes first.


Secondary Outcome Measures :
  1. Time to Progression [ Time Frame: From start of treatment until disease progression or death (up to 3 years). ]
    Time to Progression (TTP) defined as time from study treatment to RECIST progression, or death (others going off study will be censored).

  2. Drug Toxicity [ Time Frame: From start of treatment until disease progression or death (up to 3 years). ]
    Toxicity of Anetumab ravtansine assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. See adverse events for details. Participants who experienced any adverse events are included here.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Eligibility criteria for prescreening

  • Must have had at least one and not more than two prior chemotherapy regimens for advanced disease (neoadjuvant or adjuvant chemotherapy would not be counted as a line of therapy). If prior radiation, measurable lesion outside radiation portal.
  • Written informed consent for prescreening.
  • Unresectable locally advanced or metastatic pancreatic cancer, confirmed by histology
  • 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.
  • 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 or documented intolerance (neoadjuvant or adjuvant 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 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 (see Section 8.1).

  • Absolute neutrophil count (ANC) ≥ 1000/mm3
  • 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 investigator.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03023722


Locations
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United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06510
United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901-2163
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Yale University
Bayer
Investigators
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Principal Investigator: Stacey Stein, MD Yale Cancer Center, Yale University
  Study Documents (Full-Text)

Documents provided by Yale University:
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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03023722    
Other Study ID Numbers: 1608018265
First Posted: January 18, 2017    Key Record Dates
Results First Posted: January 22, 2021
Last Update Posted: January 22, 2021
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Maytansine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action