Amatuximab for High Mesothelin Cancers

• Status: Terminated
• Trial end date: 2013-11-15
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Antibodies, Monoclonal

Criteria

• 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.