Clinical trial NCT00377429: Safety and Efficacy Study of Catumaxomab to Treat Ovarian Cancer After a Complete Response to Chemotherapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Epithelial Cancer
Epithelial Carcinoma
Epithelial Ovarian Cancer
Epithelial Ovarian Carcinoma
Fallopian Tube Cancer
Fallopian Tube Carcinoma
Ovarian Cancer
Ovarian Carcinoma
Ovarian Epithelial Cancer
Ovarian Epithelial Carcinoma
Peritoneal Cancer
Peritoneal Carcinoma
Advanced Epithelial Ovarian Cancer
Lead sponsor: Neovii Biotech
Sponsor class: INDUSTRY
Collaborators: name: Fresenius Biotech North America
First posted: 2006-09-18
Enrollment: 47
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 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Completed a 4-dose Series of Catumaxomab Infusions (Defined as 10-20-50-150 Micrograms) Within 21 Days
timeFrame: 21 days
Secondary outcomes:
measure: Number of Participants With Negative (Undetectable) Humoral Immune Responses to Catumaxomab Therapy
timeFrame: 2 months
measure: Number of Participants With no Residual Disease Prior to Catumaxomab Treatment Via 2nd-look Laparoscopy or Laparotomy (These Procedures Are Optional)
timeFrame: Baseline
measure: Median Time of Progression-free Survival in Weeks (Post-study for 24 Months)
timeFrame: 2 years
measure: Number of Participants Who Survived (Post-study at 24 Month Visit)
timeFrame: 2 years
measure: Number of Participants With no Residual Disease at 3 Months After Catumaxomab Treatment Via 3rd-look Laparoscopy or Laparotomy (These Procedures Are Optional)
timeFrame: 3 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Stanford
country: United States
facility: Stanford University of Obstetrics and Gynecology
state: California
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Hinsdale
country: United States
facility: Gynecologic Oncology - Hinsdale
state: Illinois
city: South Bend
country: United States
facility: Michiana Hematology Oncology P.C.
state: Indiana
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Pittsburg
country: United States
facility: Magee-Women Hospital of UPMC
state: Pennsylvania
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
Study officials:
affiliation: Massachusetts General Hospital
name: Michael V Seiden, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
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.