A Study of MORAb-009 in Subjects With Pancreatic Cancer, Mesothelioma, or Certain Types of Ovarian or Lung Cancer

July 16, 2014 updated by: Morphotek

A Study of the Safety, Tolerability, and Pharmacokinetics of MORAb-009, a Chimeric Monoclonal Antibody, in Subjects With Advanced Mesothelin-expressing Tumors

The purpose of this study is to establish the safest doses of an investigational drug called MORAb-009 in subjects with pancreatic cancer, mesothelioma, or certain types of ovarian or lung cancer. MORAb-009 is a monoclonal antibody that is directed to an antigen on the surface of these cancers.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

MORAb-009 is a high-affinity monoclonal antibody raised against human mesothelin, a membrane glycoprotein thought to be involved in cell adhesion and tightly associated with a range of cancers. It has been shown that mesothelin is over-expressed in pancreatic cancers, mesotheliomas, and ovarian or mesothelin-expressing ovarian or non-small cell lung cancers, while showing little expression in normal tissues. Preclinical experiments indicate that MORAb-009 is a potentially useful anti-cancer agent. This clinical trial is being performed to determine the safety of MORAb-009 in subjects with mesothelin-expressing tumors, as well as to establish serum pharmacokinetics of the antibody, and to assess tumor antigens that may serve as predictors of a response to MORAb-009.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Bethesda, Maryland, United States, 20892-1922
        • National Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Female or male subjects, ≥ 18 years of age, with a histologically confirmed diagnosis of pancreatic adenocarcinoma, mesothelioma, or mesothelin-positive ovarian or non-small cell lung cancer. As nearly 100% of pancreatic adenocarcinoma and mesotheliomas express mesothelin, immunohistochemical confirmation of mesothelin-positivity is not necessary.
  • Subject must have disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) or evaluable by clinical signs/symptoms (e.g., ascites, pleural effusion, or lesions of less than 2 cm) supported by biomarker, radiologic, or pathologic studies conducted within 4 weeks prior to study entry.
  • Subject must have failed at least one standard chemotherapy regimen. Patients with pancreatic cancer must have received gemcitabine as part of prior therapy and be considered refractory, or in the case of ovarian cancer be considered platinum refractory or resistant.
  • Life expectancy ≥ 3 months, as estimated by the investigator.
  • Eastern Cooperative Oncology Group performance status or 0, 1 or 2.
  • Female subjects of childbearing potential and all male subjects must consent to use a medically acceptable method of contraception throughout the study period and for 28 days after MORAb-009 administration. A barrier method of contraception must be included.
  • Other significant medical conditions must be well controlled and stable in the opinion of the investigator for at least 30 days prior to Study Day 1.
  • Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows:

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelet count ≥ 100 x 109/L; Hemoglobin ≥ 9 g/dL; Serum bilirubin ≤ 2.0 mg/dL; Aspartate transaminase (AST) ≤ 5 x upper limit of normal (ULN); Alanine transaminase (ALT) ≤ 5 x ULN; Alkaline Phosphatase ≤ 5 x ULN; Serum creatinine ≤ 2.0 mg/dL. If the elevations of liver functions are due to obstruction of the common bile duct extrinsic to the liver, the subject may be enrolled at the discretion of the investigator even if the elevations are greater than the limits above. Stenting to reduce liver functions to qualifying levels is permitted.

- Subject must be willing and able to provide written informed consent.

Exclusion Criteria:

  • Known central nervous system (CNS) tumor involvement.
  • Evidence of other active malignancy requiring treatment.
  • Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class III or IV, angina not well controlled by medication, or myocardial infarction within 6 months).
  • ECG demonstrating clinically significant arrhythmias (Note: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal SVT, are eligible).
  • Active serious systemic disease, including active bacterial or fungal infection.
  • Active hepatitis or HIV infection.
  • Treatment within three months with immunomodulatory therapy (e.g. interferons, immunoglobulin therapy, IL-1RA or systemic corticosteroids). Short term systemic corticosteroids or topical or intra-articular steroids are acceptable, subject to the judgment of the investigator.
  • Chemotherapy, biologic therapy, or immunotherapy within 3 weeks prior to dosing with MORAb-009.
  • Breast-feeding, pregnant, or likely to become pregnant during the study.

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cohort 1
MORAb-009 weekly dose of 12.5 mg/m^2
Drug: MORAb-009
Each dose of investigational product will be given as a continuous infusion ranging from 12.5 mg/m^2 up to 400 mg/m^2.
EXPERIMENTAL: Cohort 2
MORAb-009 weekly dose of 25 mg/m^2
Drug: MORAb-009
Each dose of investigational product will be given as a continuous infusion ranging from 12.5 mg/m^2 up to 400 mg/m^2.
EXPERIMENTAL: Cohort 3
MORAb-009 weekly dose of 50 mg/m^2
Drug: MORAb-009
Each dose of investigational product will be given as a continuous infusion ranging from 12.5 mg/m^2 up to 400 mg/m^2.
EXPERIMENTAL: Cohort 4
MORAb-009 weekly dose of 100 mg/m^2
Drug: MORAb-009
Each dose of investigational product will be given as a continuous infusion ranging from 12.5 mg/m^2 up to 400 mg/m^2.
EXPERIMENTAL: Cohort 5
MORAb-009 weekly dose of 200 mg/m^2
Drug: MORAb-009
Each dose of investigational product will be given as a continuous infusion ranging from 12.5 mg/m^2 up to 400 mg/m^2.
EXPERIMENTAL: Cohort 6
MORAb-009 weekly dose of 400 mg/m^2
Drug: MORAb-009
Each dose of investigational product will be given as a continuous infusion ranging from 12.5 mg/m^2 up to 400 mg/m^2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety and Tolerability as a measure of Adverse Events/Serious Adverse Events
Time Frame: 35 day treatment and observation period, or until disease progession occurs
35 day treatment and observation period, or until disease progession occurs
Safety and Tolerability as a measure of clinical laboratory parameters
Time Frame: 35 day treatment and observation period, or until disease progession occurs
35 day treatment and observation period, or until disease progession occurs
Safety and Tolerability as a measure of physical examinations, vital signs, and ECGs
Time Frame: 35 day treatment and observation period, or until disease progession occurs
35 day treatment and observation period, or until disease progession occurs

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of MORAb-009
Time Frame: Pre-dose, mid-infusion, end of infusion, 30 min, 60 min, 2 hours, and 4 hours post dose
Blood samples will be analyzed using ELISA for concentration of MORAb-009.
Pre-dose, mid-infusion, end of infusion, 30 min, 60 min, 2 hours, and 4 hours post dose
Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA])
Time Frame: 35 day treatment and observation period
35 day treatment and observation period
Objective Tumor Response Rate Assessed by Investigator
Time Frame: 35 day treatment and observation period
CT; MRI; RECIST criteria; biomarkers
35 day treatment and observation period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Morphotek

Study record dates

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 Major Dates

Study Start

May 1, 2006

Primary Completion (ACTUAL)

September 1, 2008

Study Completion (ACTUAL)

September 1, 2008

Study Registration Dates

First Submitted

May 11, 2006

First Submitted That Met QC Criteria

May 11, 2006

First Posted (ESTIMATE)

May 12, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

July 17, 2014

Last Update Submitted That Met QC Criteria

July 16, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MORAb-009-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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