Amatuximab for High Mesothelin Cancers

December 14, 2019 updated by: National Cancer Institute (NCI)

A Single-Dose Pilot Study of Radiolabeled Amatuximab (MORAb-009) in Mesothelin Over Expressing Cancers

Background:

- Amatuximab is a cancer treatment drug that targets mesothelin. High levels of this substance are found on some kinds of tumor cells. Lab studies have shown that amatuximab helps the immune system to kill cells that have high levels of mesothelin. However, more research is needed to determine how safe and effective amatuximab is for treating tumors with high levels of mesothelin.

Objectives:

- To assess the safety and effectiveness of amatuximab in treating tumors with high levels of mesothelin.

Eligibility:

- Individuals at least 18 years of age who have a type of cancer that overexpresses mesothelin.

Design:

  • Participants will be screened with a medical history and physical exam. They will also have blood tests and tumor assessment studies.
  • Participants will have two intravenous doses of amatuximab several hours apart. Researchers will monitor them closely and do frequent blood draws. On the same day and also within 48 hours of the second dose, participants will have imaging studies. These studies will measure how well the amatuximab is working against the cancer.
  • Participants will have a third imaging study of the cancer about 1 week after the infusions.
  • Participants will have a followup visit 2 weeks after receiving amatuximab. This visit will require blood samples. Four weeks after receiving the drug, researchers will review patients symptoms or side effects. This interview can be done in person or by phone.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Background:

  • Amatuximab is a high-affinity monoclonal IgG antibody raised against human mesothelin.
  • Mesothelin is a glycosyl-phosphatidyl inositol-linked membrane glycoprotein thought to be involved in tumor metastasis
  • Mesothelin is over-expressed in many cancers

Objectives:

-The primary objective is to determine the biodistribution of radiolabeled amatuximab in tumor and nontumor tissues in subjects with mesothelin over-expressing cancers including mesothelioma, pancreatic, ovarian, and non small cell lung cancer.

Eligibility:

  • Female or male subjects greater than or equal to 18 years of age;
  • Histologically confirmed mesothelin-expressing cancer;
  • Transaminases less than or equal to 3 times ULN for mesothelioma, non small cell lung and ovarian cancer;
  • Transaminases less than or equal to 5 times ULN for pancreatic cancer with known liver metastasis.

Design:

  • This is a single-center, single-dose, open-label, pilot study of MORAb-009 in approximately 20 subjects with mesothelin expressing tumors.
  • Indium-radiolabeled MORAb-009 (5mCi) will be administered.
  • Serial single photon emission-computerized tomography imaging will be performed to determine binding to tumor and nontumor tissue.
  • Subjects will be observed closely for safety and possible development of anti-MORAb-009 antibodies.
  • Pharmacokinetics of radiolabeled antibody will be determined with imaging over time.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Early 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
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

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 to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:
  • Female or male subjects, greater than or equal to 18 years of age.
  • Histologically-confirmed diagnosis of pancreatic adenocarcinoma, mesothelioma, mesothelin-positive ovarian cancer, or NSCLC. A new biopsy is not required; the diagnostic biopsy sample will be sufficient. IHC confirmation of mesothelin-positivity is not necessary for pancreatic adenocarcinoma and mesothelioma as nearly 100% of pancreatic adenocarcinomas and mesotheliomas express mesothelin. Mesothelin expression in ovarian cancer and NSCLC will be tested by IHC and any degree of positivity (1+, 2+, or 3+) will be accepted.
  • Subjects are required to have measurable disease that has progressed through prior therapy and that includes a non-hepatic lesion for imaging that is greater than or equal to 1.5 cm, as defined by Modified Response Evaluation Criteria in Solid Tumors (RECIST).
  • Eastern Cooperative Oncology Group (ECOG) performance status or 0, 1, or 2.
  • Female subjects of childbearing potential and all male subjects are required to consent to use a medically acceptable method of contraception throughout the study period and for 30 days after amatuximab administration. A barrier method of contraception is required.

  • Laboratory and clinical results within the 2 weeks prior to Day of Infusion as follows:

    • Absolute neutrophil count (ANC): greater than or equal to 1.5 times 10(9)/L
    • Platelet count: greater than or equal to 75 times 10(9)/L
    • Hemoglobin: greater than or equal to 9 g/dL
    • Serum bilirubin: less than or equal to 1.5 mg/dL
    • Aspartate transaminase (AST): less than or equal to 3 x upper limit of normal (ULN) (less than or equal to 5 ULN acceptable for pancreatic patients with known liver metastasis only)
    • Alanine transaminase (ALT) less than or equal to 3 times upper limit of normal (ULN) (less than or equal to 5 ULN acceptable for pancreatic patients with known liver metastasis only)
    • Alkaline Phosphatase less than or equal to 5 times ULN
    • Serum creatinine less than or equal to 1.5 mg/dL
  • Subjects are required to be willing and able to provide written informed consent.

EXCLUSION CRITERIA:

  • Subjects are ineligible to participate in this study if any of the following criteria are met:

    • Known allergy or hypersensitivity to monoclonal antibodies;
    • Prior treatment with amatuximab;
    • Prior treatment with SS1(dsFv)PE38 (SS1P);
    • Known brain metastases;
    • Known prosthetic devices that would prohibit imaging of lesion of interest due to radiographic artifact;
    • 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. Subjects with chronic atrial arrhythmia, (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia), are eligible;
    • Active serious systemic disease, including active bacterial or fungal infection within 2 weeks before study entry;
    • Active viral hepatitis or symptomatic human immunodeficiency virus (HIV) infection;
    • Treatment within 3 months with immunomodulatory therapy (e.g., interferons, immunoglobulin therapy, Interleukin 1 receptor antagonist (IL-1RA) or systemic corticosteroids). Short-term systemic corticosteroids or topical or intra-articular steroids are acceptable, at the discretion of the Investigator;
    • Chemotherapy, biologic therapy, radiation therapy or immunotherapy within 3 weeks prior to dosing with amatuximab;
    • 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 Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Biodistribution of radiolabelled amatuximab in tumor and nontumor tissues.
Tumor
Background ratio of maximum counts

Secondary Outcome Measures

Outcome Measure
CTCAE V.4 events
Observation of HACA
PKs
Antibody uptake vs. IHC mesothelin expression

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

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

General Publications

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

July 12, 2011

Primary Completion (Actual)

November 15, 2013

Study Completion (Actual)

November 15, 2013

Study Registration Dates

First Submitted

August 9, 2011

First Submitted That Met QC Criteria

August 9, 2011

First Posted (Estimate)

August 10, 2011

Study Record Updates

Last Update Posted (Actual)

December 17, 2019

Last Update Submitted That Met QC Criteria

December 14, 2019

Last Verified

November 15, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 110212
  • 11-C-0212

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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