Safety and Efficacy Study of Catumaxomab to Treat Ovarian Cancer After a Complete Response to Chemotherapy

An Open-Label, Single-Arm, Phase II Safety and Tolerability Study of Catumaxomab (Anti-EpCAM x Anti-CD3) in Women With Advanced Epithelial Ovarian Cancer After a Complete Response to Chemotherapy

The purpose of this study is to determine whether the investigational drug catumaxomab delivered in the planned treatment schedule is a safe and effective treatment for women with advanced ovarian cancer who experience a complete response to chemotherapy.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: catumaxomab

Detailed Description

A multi-center, phase II study of catumaxomab in ovarian cancer patients who experience a complete response to chemotherapy. Each eligible patient will receive four ascending doses of catumaxomab, administered intraperitoneally via an indwelling catheter or port. 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 4 months (includes the baseline screening period, 11 to 21 days treatment period, and up to 90 days/3 months follow-up), with post-study follow-up every 3 months for 2 years.

Catumaxomab is a trifunctional antibody targeting epithelial cell adhesion molecule (EpCAM) on tumor cells and CD3 (cluster of differentiation 3) 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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • California
    • Stanford, California, United States, 94305
      • Stanford University of Obstetrics and Gynecology
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Gynecologic Oncology - Hinsdale
  • Indiana
    • South Bend, Indiana, United States, 46617
      • Michiana Hematology Oncology P.C.
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Pittsburg, Pennsylvania, United States, 15213
      • Magee-Women Hospital of UPMC
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Signed and dated informed consent form before any protocol-specific screening procedures
• Histologically confirmed diagnosis of epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIb - IV
• Optimal or sub-optimal cytoreductive surgery
• Clinical complete response to platinum and taxane-based therapy consisting of at least four cycles, based on computed tomography (CT) scan and a CA-125 (cancer antigen 125) level below 35 U/mL
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Last dose of platinum and taxane-based therapy completed within 6 weeks prior to the start of catumaxomab treatment
• 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 chemotherapy, radiotherapy, immunotherapy or investigational anti-cancer therapy within 6 weeks of first dose of catumaxomab other than last regimen of platinum and taxane chemotherapy as outlined in protocol
• Known human immunodeficiency virus (HIV) infection
• Previous treatment with non-humanized murine (rat or mouse) monoclonal antibodies (mAb)
• Inadequate renal function (creatinine > 1.5 x upper limit of normal [ULN])

• Inadequate hepatic function:

  • Alanine aminotransferase (ALT) > 2.5 x ULN or
  • Aspartate aminotransferase (AST) > 2.5 x ULN or
  • Bilirubin > 1.5 x ULN
• Platelets < 100,000 cells/mm^3
• Absolute neutrophil count (ANC) < 1,500 cells/mm^3
• History of myocardial infarction, congestive heart failure or relevant cardiac arrhythmia within the last 6 months
• No other malignancy within the past 5 years except non-melanoma skin cancer or carcinoma in situ of the cervix if adequately treated
• No history of brain metastases
• Any further condition or disease that would, in the opinion of the Investigator, expose the patient to undue risk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: catumaxomab	Drug: catumaxomab; Catumaxomab administered as four 3-hour, constant-rate, intraperitoneal (IP) infusions of 10, 20, 50, 150 microgram (mcg).; Other Names: Removab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Completed a 4-dose Series of Catumaxomab Infusions (Defined as 10-20-50-150 Micrograms) Within 21 Days	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Negative (Undetectable) Humoral Immune Responses to Catumaxomab Therapy	Humoral immune response of participants with functional immune system to catumaxomab can provide important information regarding why a therapy may work for some participants and not for others. An undetectable humoral response by itself does not necessarily imply lack of study drug activity. Humoral response is one of the possible selected measurements of the study drug activity at a time point in the study.	2 months
Number of Participants With no Residual Disease Prior to Catumaxomab Treatment Via 2nd-look Laparoscopy or Laparotomy (These Procedures Are Optional)		Baseline
Median Time of Progression-free Survival in Weeks (Post-study for 24 Months)		2 years
Number of Participants Who Survived (Post-study at 24 Month Visit)	Number of participants who survived (post-study at 24 month visit) is the number of participants who did not die	2 years
Number of Participants With no Residual Disease at 3 Months After Catumaxomab Treatment Via 3rd-look Laparoscopy or Laparotomy (These Procedures Are Optional)		3 months

Collaborators and Investigators

• Sponsor: Neovii Biotech
• Collaborators: Fresenius Biotech North America
• Investigators: Principal Investigator: Michael V Seiden, MD, Ph.D, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (ACTUAL): February 1, 2008
• Study Completion (ACTUAL): February 1, 2008

Study Registration Dates

• First Submitted: September 15, 2006
• First Submitted That Met QC Criteria: September 15, 2006
• First Posted (ESTIMATE): September 18, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): July 19, 2012
• Last Update Submitted That Met QC Criteria: July 16, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Epithelial Ovarian Cancer; Ovarian Cancer; Ovarian Epithelial Cancer; Ovarian Carcinoma; Peritoneal Cancer; Fallopian Tube Cancer; Epithelial Cancer; Epithelial Carcinoma; Epithelial Ovarian Carcinoma; Fallopian Tube Carcinoma; Ovarian Epithelial Carcinoma; Peritoneal Carcinoma; Advanced Epithelial Ovarian Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Gastrointestinal Agents; Catumaxomab
• Other Study ID Numbers: IP-CAT-OC-01