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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-01-13	Results First Submitted 2020-11-05	Last Update Submitted that met QC Criteria 2021-10-11
First Submitted that Met QC Criteria 2017-01-13	Results First Submitted that Met QC Criteria 2021-01-04	Last Update Posted (ACTUAL) 2021-10-28
First Posted (ACTUAL) 2017-01-18	Results First Posted 2021-01-22	Last Verified 2021-10

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/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

Participant Group/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	Measure Description	Time Frame
Response Rate as Measured Per RECIST 1.1 Criteria	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.	From start of treatment until disease progression or death (up to 3 years).

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

Age ≥ 18 years.
Life expectancy of at least 3 months.
No prior treatment with anetumab ravtansine (or any other mesothelin-based therapy)

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).

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.

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

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

Collaborators and Investigators

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Learn

Resources

PatientS

Caregivers

Clinical Trial Record