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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00325494
• Other study ID #: MORAb-009-001
• Status: Completed
• Phase: Phase 1
• First received: May 11, 2006
• Last updated: July 16, 2014
• Start date: May 2006
• Est. completion date: September 2008

Study information

• Verified date: July 2014
• Source: Morphotek
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00377013
• NCT00349154

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Mesothelioma
• Non-Small Cell Lung Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	National Cancer Institute	Bethesda	Maryland
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Morphotek

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability as a measure of Adverse Events/Serious Adverse Events		35 day treatment and observation period, or until disease progession occurs	Yes
Primary	Safety and Tolerability as a measure of clinical laboratory parameters		35 day treatment and observation period, or until disease progession occurs	No
Primary	Safety and Tolerability as a measure of physical examinations, vital signs, and ECGs		35 day treatment and observation period, or until disease progession occurs	No
Secondary	Pharmacokinetics of MORAb-009	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	No
Secondary	Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA])		35 day treatment and observation period	No
Secondary	Objective Tumor Response Rate Assessed by Investigator	CT; MRI; RECIST criteria; biomarkers	35 day treatment and observation period	No