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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00377429
• Other study ID #: IP-CAT-OC-01
• Status: Completed
• Phase: Phase 2
• First received: September 15, 2006
• Last updated: July 16, 2012
• Start date: September 2006
• Est. completion date: February 2008

Study information

• Verified date: July 2012
• Source: Neovii Biotech
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• catumaxomab
Catumaxomab administered as four 3-hour, constant-rate, intraperitoneal (IP) infusions of 10, 20, 50, 150 microgram (mcg).

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	Gynecologic Oncology - Hinsdale	Hinsdale	Illinois
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Magee-Women Hospital of UPMC	Pittsburg	Pennsylvania
United States	Michiana Hematology Oncology P.C.	South Bend	Indiana
United States	Stanford University of Obstetrics and Gynecology	Stanford	California
United States	Arizona Cancer Center	Tucson	Arizona
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Neovii Biotech	Fresenius Biotech North America

Country where clinical trial is conducted

United States, 

References & Publications (5)

Heiss MM, Ströhlein MA, Jäger 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. — View 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. — View 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. — View Citation

Zeidler R, Mysliwietz J, Csánady 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Completed a 4-dose Series of Catumaxomab Infusions (Defined as 10-20-50-150 Micrograms) Within 21 Days		21 days	Yes
Secondary	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	No
Secondary	Number of Participants With no Residual Disease Prior to Catumaxomab Treatment Via 2nd-look Laparoscopy or Laparotomy (These Procedures Are Optional)		Baseline	No
Secondary	Median Time of Progression-free Survival in Weeks (Post-study for 24 Months)		2 years	No
Secondary	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	No
Secondary	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	No

External Links

•   Link