Clinical trial NCT00326885: Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites
Official title: A Single-Arm, Open-Label, Phase II Study to Assess the Safety and Efficacy of the Trifunctional Antibody Catumaxomab (Anti-EpCAM x Anti-CD3) Administered Intraperitoneally in Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Ascites
Keywords: Ascites
Epithelial Cancer
Epithelial Carcinoma
Epithelial Ovarian Cancer
Epithelial Ovarian Carcinoma
Fallopian Tube Cancer
Fallopian Tube Carcinoma
Malignant Ascites
Ovarian Cancer
Ovarian Carcinoma
Ovarian Epithelial Cancer
Ovarian Epithelial Carcinoma
Peritoneal Cancer
Peritoneal Carcinoma
Recurrent Ascites
Recurrent Malignant Ascites
Recurrent Symptomatic Malignant Ascites
Symptomatic Malignant Ascites
Symptomatic Ascites
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Lead sponsor: Neovii Biotech
Sponsor class: INDUSTRY
Collaborators: name: Fresenius Biotech North America
First posted: 2006-05-17
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Proportion of Patients Who Achieved at Least a 4-fold Increase of Puncture/Paracentesis-free Interval Following Catumaxomab Relative to Their Pre-treatment Interval.
timeFrame: 6 months
measure: Increase of Paracentesis/Puncture-free Interval (Ratio)
timeFrame: 180 days
Secondary outcomes:
measure: Puncture/Paracentesis-free Survival (PuFS)
timeFrame: ≥6 months
measure: Overall Survival (OS)
timeFrame: ≥ 6 months
measure: Ascites Signs and Symptoms
timeFrame: 6 months
measure: Ascites Volume
timeFrame: 6 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: University of San Diego
state: California
city: Stanford
country: United States
facility: Stanford University Hospital and Clinics
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Center
state: Florida
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Louisville
country: United States
facility: University of Louisville Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institute
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Columbia University Cancer center
state: New York
city: Winston-Salem
country: United States
facility: Wake-Forest University
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: Magee Women's Hospital, University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Stanford University Hospital and Clinics, Department of Obstetrics and Gynecology
name: Jonathan Berek, MD MMSc
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.