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

NCT00326885 | Completed Phase 2 Results

• 1 other identifier: IP-REM-AC-02-US
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 18

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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

  The parameter to be estimated is the proportion of patients who achieve at least a 4-fold increase in their puncture/paracentesis-free interval. The pretreatment interval is defined as the length of time between the patient's most recent paracentesis (baseline) and the subsequent paracentesis necessitated by her increasing ascites-related symptoms. The post-treatment interval is defined as the time between the last dose of catumaxomab plus 1 day to the time of recurrence of ascites requiring therapeutic paracentesis or death, whichever occurred sooner.

  6 months

• Increase of Paracentesis/Puncture-free Interval (Ratio)

  The parameter to be tested is the ratio of the post-treatment puncture/paracentesis-free interval divided by the pre-treatment puncture/paracentesis-free interval. The pre-treatment interval is defined as the length of time between the patient's most recent paracentesis (baseline) and the subsequent paracentesis necessitated by her increasing ascites-related symptoms. The post-treatment interval is defined as the time between the last dose of catumaxomab plus 1 day to the time of recurrence of ascites requiring therapeutic paracentesis or death, whichever occurred sooner.

  180 days

Secondary Outcomes (4)

• Puncture/Paracentesis-free Survival (PuFS)

  ≥6 months

• Overall Survival (OS)

  ≥ 6 months

• Ascites Signs and Symptoms

  6 months

• Ascites Volume

  6 months

Study Arms (1)

Catumaxomab

EXPERIMENTAL

Drug: catumaxomab

Interventions

catumaxomab 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).

Catumaxomab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Neovii Biotech: lead
• Fresenius Biotech North America: collaborator

Study Sites (18)

University of Arizona Cancer Center

Tucson, Arizona, United States

Location

University of San Diego

La Jolla, California, United States

Location

Stanford University Hospital and Clinics

Stanford, California, United States

Location

University of Miami

Miami, Florida, United States

Location

Florida Hospital Cancer Center

Orlando, Florida, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Location

University of Louisville Cancer Center

Louisville, Kentucky, United States

Location

Johns Hopkins Medical Institute

Baltimore, Maryland, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, United States

Location

Wayne State University

Detroit, Michigan, United States

Location

Dartmouth-Hitchock Medical Center

Lebanon, New Hampshire, United States

Location

Columbia University Cancer center

New York, New York, United States

Location

Wake-Forest University

Winston-Salem, North Carolina, United States

Location

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, United States

Location

Magee Women's Hospital, University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Location

The Methodist Hospital

Houston, Texas, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Location

Related Publications (8)

• 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.

  PMID: 15906359 BACKGROUND

• 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.

  PMID: 11588051 BACKGROUND

• 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.

  PMID: 11410615 BACKGROUND

• 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.

  PMID: 10901380 BACKGROUND

• 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.

  PMID: 10415020 BACKGROUND

• 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.

  PMID: 20473913 BACKGROUND

• 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.

  PMID: 20565453 BACKGROUND

• 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.

  PMID: 25254563 DERIVED

MeSH Terms

Conditions

Ascites; Carcinoma; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Ovarian Neoplasms; Neoplasms, Glandular and Epithelial; Peritoneal Neoplasms

Interventions

catumaxomab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Results Point of Contact

• Title: Manager, Regulatory Affairs
• Organization: Fresenius Biotech

bao.le@fresenius-biotech.com

781-699-4652

Study Officials

• Jonathan Berek, MD MMSc

  Stanford University Hospital and Clinics, Department of Obstetrics and Gynecology

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2006
• First Posted: May 17, 2006
• Study Start: June 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: August 1, 2010
• Last Updated: October 17, 2018
• Results First Posted: December 11, 2012

Record last verified: 2018-09

Locations

US (18)