Brief Title
Amatuximab for High Mesothelin Cancers
Official Title
A Single-Dose Pilot Study of Radiolabeled Amatuximab (MORAb-009) in Mesothelin Over Expressing Cancers
Brief 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.
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 Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Biodistribution of radiolabelled amatuximab in tumor and nontumor tissues.
Secondary Outcome
CTCAE V.4 events
Condition
Carcinoma, Pancreatic Ductal
Intervention
Amatuximab (MORab-009)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
7
Start Date
July 12, 2011
Completion Date
November 15, 2013
Primary Completion Date
November 15, 2013
Eligibility 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.
Gender
All
Ages
18 Years - 100 Years
Accepts Healthy Volunteers
No
Contacts
Raffit Hassan, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01413451
Organization ID
110212
Secondary IDs
11-C-0212
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Raffit Hassan, M.D., Principal Investigator, National Cancer Institute (NCI)
Verification Date
November 15, 2013