Clinical trial NCT00464893: Phase II Study With Catumaxomab in Patients With Gastric Cancer After Neoadjuvant CTx and Curative Resection
Official title: Multicenter, Open-label Phase II Study to Evaluate the Safety and Efficacy of the Trifunctional Bispecific Antibody Catumaxomab (Anti-EpCAM x Anti-CD3) in Patients With Gastric Adenocarcinoma After Neoadjuvant Chemotherapy and Intended Curative Resection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Cancer
Gastric Adenocarcinoma
Keywords: gastric cancer
catumaxomab
neoadjuvant chemotherapy
phase II
interoperative
trifunctional antibody
Lead sponsor: Neovii Biotech
Sponsor class: INDUSTRY
First posted: 2007-04-24
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary evaluation of the safety, tolerability and feasibility regarding specific postoperative complications of an adjuvant treatment with catumaxomab administered after curative tumor resection subsequent to a neoadjuvant chemotherapy.

Detailed description: An open-label, multi-center phase II study in surgically resectable patients after neoadjuvant ECX-chemotherapy, with confirmed diagnosis of gastric adenocarcinoma and with a high risk of disseminated tumor cells due to serosal infiltration or positive lymph nodes after curative gastrectomy.

Treatment with catumaxomab will consist of an initial dose of 10 µg given intraoperatively as an intraperitoneal bolus and of four postoperative ascending doses (10-20-50-150 µg)which will be administered as an i.p.-infusion using an installed abdominal i.p.-port on the postoperative days 7, 10, 13 and 16.

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
* male or female patient at an age of 18 years or older
* patient has a primary diagnosis of a histologically confirmed gastric adenocarcinoma (including GE junction Siewert-Type 2 or 3)
* TNM-staging at screening of T3/T4, N+/-, M0 or T2, N+, M0
* indication and eligibility for a neoadjuvant chemotherapeutic regimen featuring three cycles of ECX with 21 days per cycle
* intended curative gastrectomy
* Karnofsky index \> 70

Exclusion Criteria:

* Exposure to prior cancer therapy or planned adjuvant chemo- or radiotherapy of the current gastric cancer
* prior diagnosis of any malignancy not cured by surgery alone less than 5 years before study entry
* previous use of non-humanized monoclonal mouse or rat antibodies
* treatment with another investigational product during this study or during the last 30 days prior to study start
* presence of distant metastases
* presence of constant immunosuppressive therapy
* history of pancreas resection (also partial) or thoracotomy
* presence of any acute or chronic systemic infection
* patient with a bowel obstruction within the last 30 days
* known contraindications to any of the planned ECX chemotherapeutics

Primary outcomes:
measure: rate of all specific postoperative complications newly observed during a period of 30 days after surgery in those study patients who received at least the first 3 doses of catumaxomab
timeFrame: 30 days after last catumaxomab administration
Secondary outcomes:
measure: frequency, relationship and seriousness of adverse events
timeFrame: 30 days after last catumaxomab administration
measure: surgical resection rate
timeFrame: after surgery
measure: chemotherapeutic response rate
timeFrame: after neoadjuvant CTx
measure: overall survival at 3, 6, 9, 12 and 24 month after EOT, defined as the time from study enrolment until death
timeFrame: 2 years
measure: disease-free survival at 3, 6, 9, 12 18 and 24 months after EOT, defined as the time from study enrolment to the point of diagnosis of recurrent disease or death, whichever occurred first
timeFrame: 2 years
Other outcomes:
Locations:
city: Innsbruck
country: Austria
city: Hamburg, Berlin, Heidelberg, Köln, Halle
country: Germany
city: Terrassa
country: Spain
city: Nottingham
country: United Kingdom
Study officials:
affiliation: University Clinic of Hamburg-Eppendorf; 20246 Hamburg / Germany
name: Carsten Bokemeyer, Prof MD
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.