Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites

NCT ID: NCT00326885

Last Updated: 2018-10-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-06-30

Study Completion Date

2010-08-31

Brief Summary

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The purpose of this study is to determine whether the investigational drug catumaxomab is a safe and effective treatment for recurrent symptomatic malignant ascites.

Detailed Description

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A multi-center, phase II study of catumaxomab in ovarian cancer patients with recurrent symptomatic malignant ascites requiring therapeutic paracentesis. Each eligible patient will receive four ascending doses of catumaxomab, administered intraperitoneally via an indwelling catheter. Catumaxomab will be administered as a 3-hour constant rate infusion with a dosing interval of 3-4 days. Each patient will participate in this study for up to 7 months (includes the baseline therapeutic paracentesis and screening period, 11 to 21 days treatment period, and up to 180 days/6 months follow-up), with monthly post-study follow-up for the lifetime of the patient.

Catumaxomab is a trifunctional antibody targeting EpCAM on tumor cells and CD3 on T cells. Trifunctional antibodies represent a new concept for targeted anticancer therapy. This new antibody class has the capability to redirect T cells and accessory cells (e.g. macrophages, dendritic cells (DCs) and natural killer (NK) cells) to the tumor site. According to preclinical data, trifunctional antibodies activate these different immune effector cells, which can trigger a complex anti-tumor immune response.

Conditions

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Malignant Ascites

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Catumaxomab

Group Type EXPERIMENTAL

catumaxomab

Intervention Type DRUG

Catumaxomab is administered intraperitoneally via an indwelling catheter (or port) as a 3-hour infusion 4 times (Days 0, 3, 7, and 10) in ascending doses (10 mcg, 20 mcg, 50 mcg, and 150 mcg, respectively).

Interventions

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catumaxomab

Catumaxomab is administered intraperitoneally via an indwelling catheter (or port) as a 3-hour infusion 4 times (Days 0, 3, 7, and 10) in ascending doses (10 mcg, 20 mcg, 50 mcg, and 150 mcg, respectively).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Signed and dated informed consent
* Histologically confirmed diagnosis of epithelial ovarian cancer, peritoneal cancer, or fallopian tube cancer; any stage at diagnosis \[International Federation of Gynecology and Obstetrics (FIGO) Stages I through IV\].
* Progression on or ≤ 12 months after primary platinum-based systemic or intraperitoneal (IP) chemotherapy OR relapse following reinduction ≥ 12 months after primary chemotherapy.
* Have refused, failed, or have been deemed not suitable candidates for gemcitabine or liposomal doxorubicin.
* Recurrent symptomatic malignant ascites requiring therapeutic paracentesis
* At least 1 therapeutic paracentesis within 4 weeks prior to baseline paracentesis
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Life expectancy ≥ 16 weeks
* Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, and total bilirubin ≤ 1.5 x ULN
* Absolute neutrophil count (ANC) ≥ 1,500/mm3 and platelet count ≥ 75,000/mm3
* Negative serum pregnancy test result at screening in women of childbearing potential (applies to patients without documented menopause or sterility).
* Willingness of patients of childbearing potential to use an effective contraceptive method (i.e., oral contraceptive, cervical cap, diaphragm with spermicide, condom with spermicide, or intrauterine device) during the study and for at least 6 months after the last infusion.

Exclusion Criteria

* Acute or chronic systemic infection
* Exposure to investigational drugs, chemotherapy or radiotherapy 21 days prior to the first dose of catumaxomab
* Major surgery 2 weeks prior to first dose
* Previous treatment with mouse or rat antibodies
* Known or suspected hypersensitivity to catumaxomab or other monoclonal antibodies
* Body mass index (BMI) \< 19 (body weight after paracentesis to be used for calculation of BMI)
* Serum albumin level \< 2.0 g/dL
* Reduced nutritional status requiring predominantly parenteral nutrition (\> 50% of energy intake). Permanent naso-gastric (NG) feeding tube.
* Ileus in a location that precludes paracentesis
* Extensive liver metastases (\> 70% organ volume comprises malignancy)
* Documented brain metastases
* History of myocardial infarction, congestive heart failure or relevant cardiac arrhythmia 3 months prior to the first dose of catumaxomab
* Portal vein obstruction or portal vein thrombosis diagnosed by computed tomography (CT) scan at screening
* Persistent massive pleural effusion or inadequate respiratory function of any other etiology (except if related to ascites symptoms) in the opinion of the investigator
* Any other condition which, according to the investigator, results in an undue risk to the patient by participating in the study
* Prior exposure to catumaxomab
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Fresenius Biotech North America

INDUSTRY

Sponsor Role collaborator

Neovii Biotech

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan Berek, MD MMSc

Role: STUDY_CHAIR

Stanford University Hospital and Clinics, Department of Obstetrics and Gynecology

Locations

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University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of San Diego

La Jolla, California, United States

Site Status

Stanford University Hospital and Clinics

Stanford, California, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Florida Hospital Cancer Center

Orlando, Florida, United States

Site Status

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Site Status

University of Louisville Cancer Center

Louisville, Kentucky, United States

Site Status

Johns Hopkins Medical Institute

Baltimore, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

Dartmouth-Hitchock Medical Center

Lebanon, New Hampshire, United States

Site Status

Columbia University Cancer center

New York, New York, United States

Site Status

Wake-Forest University

Winston-Salem, North Carolina, United States

Site Status

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, United States

Site Status

Magee Women's Hospital, University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

The Methodist Hospital

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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Heiss MM, Strohlein MA, Jager M, Kimmig R, Burges A, Schoberth A, Jauch KW, Schildberg FW, Lindhofer H. Immunotherapy of malignant ascites with trifunctional antibodies. Int J Cancer. 2005 Nov 10;117(3):435-43. doi: 10.1002/ijc.21165.

Reference Type BACKGROUND
PMID: 15906359 (View on PubMed)

Ruf P, Lindhofer H. Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. Blood. 2001 Oct 15;98(8):2526-34. doi: 10.1182/blood.v98.8.2526.

Reference Type BACKGROUND
PMID: 11588051 (View on PubMed)

Riesenberg R, Buchner A, Pohla H, Lindhofer H. Lysis of prostate carcinoma cells by trifunctional bispecific antibodies (alpha EpCAM x alpha CD3). J Histochem Cytochem. 2001 Jul;49(7):911-7. doi: 10.1177/002215540104900711.

Reference Type BACKGROUND
PMID: 11410615 (View on PubMed)

Zeidler R, Mysliwietz J, Csanady M, Walz A, Ziegler I, Schmitt B, Wollenberg B, Lindhofer H. The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells. Br J Cancer. 2000 Jul;83(2):261-6. doi: 10.1054/bjoc.2000.1237.

Reference Type BACKGROUND
PMID: 10901380 (View on PubMed)

Zeidler R, Reisbach G, Wollenberg B, Lang S, Chaubal S, Schmitt B, Lindhofer H. Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing. J Immunol. 1999 Aug 1;163(3):1246-52.

Reference Type BACKGROUND
PMID: 10415020 (View on PubMed)

Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, Dudnichenko AS, Aleknaviciene B, Razbadauskas A, Gore M, Ganea-Motan E, Ciuleanu T, Wimberger P, Schmittel A, Schmalfeldt B, Burges A, Bokemeyer C, Lindhofer H, Lahr A, Parsons SL. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial. Int J Cancer. 2010 Nov 1;127(9):2209-21. doi: 10.1002/ijc.25423.

Reference Type BACKGROUND
PMID: 20473913 (View on PubMed)

Ruf P, Kluge M, Jager M, Burges A, Volovat C, Heiss MM, Hess J, Wimberger P, Brandt B, Lindhofer H. Pharmacokinetics, immunogenicity and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patients. Br J Clin Pharmacol. 2010 Jun;69(6):617-25. doi: 10.1111/j.1365-2125.2010.03635.x.

Reference Type BACKGROUND
PMID: 20565453 (View on PubMed)

Berek JS, Edwards RP, Parker LP, DeMars LR, Herzog TJ, Lentz SS, Morris RT, Akerley WL, Holloway RW, Method MW, Plaxe SC, Walker JL, Friccius-Quecke H, Krasner CN. Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: a phase II study. Int J Gynecol Cancer. 2014 Nov;24(9):1583-9. doi: 10.1097/IGC.0000000000000286.

Reference Type DERIVED
PMID: 25254563 (View on PubMed)

Other Identifiers

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IP-REM-AC-02-US

Identifier Type: -

Identifier Source: org_study_id

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