Phase II Study With Catumaxomab in Patients With Gastric Cancer After Neoadjuvant CTx and Curative Resection - Full Text View

Purpose

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.

Condition	Intervention	Phase
Gastric Cancer Gastric Adenocarcinoma	Drug: Catumaxomab Drug: catumaxomab	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Stomach Cancer

U.S. FDA Resources

Further study details as provided by Fresenius Biotech GmbH:

Primary Outcome Measures:

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 [ Time Frame: 30 days after last catumaxomab administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

frequency, relationship and seriousness of adverse events [ Time Frame: 30 days after last catumaxomab administration ] [ Designated as safety issue: Yes ]
surgical resection rate [ Time Frame: after surgery ] [ Designated as safety issue: No ]
chemotherapeutic response rate [ Time Frame: after neoadjuvant CTx ] [ Designated as safety issue: No ]
overall survival at 3, 6, 9, 12 and 24 month after EOT, defined as the time from study enrolment until death [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	70
Study Start Date:	April 2007
Estimated Study Completion Date:	July 2013
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: catumaxomab arm Patients will get first the chemotherapeutic regimen (Epirubicin, Cisplatin and Capecitabine or 5-Fluorouracil) consisting of three 21-day cycles, starting on the weeks 1, 4 and 7. Four weeks after CTx the D2 surgery will take place. Treatment with catumaxomab will consist of an initial dose of 10µg given intraoperatively as in intraperitoneal bolus and of four postoperative ascending doses.	Drug: Catumaxomab 10 µg intraoperative and 4 ascending doses (10, 20, 50 and 150 µg) on day 7, 10, 13 and 16 Other Name: Removab Drug: catumaxomab 10 µg intraoperatively and 4 ascending doses: 10, 20, 50 and 150 µg Other Name: Removab

Arms

Assigned Interventions

Active Comparator: catumaxomab arm

Patients will get first the chemotherapeutic regimen (Epirubicin, Cisplatin and Capecitabine or 5-Fluorouracil) consisting of three 21-day cycles, starting on the weeks 1, 4 and 7. Four weeks after CTx the D2 surgery will take place. Treatment with catumaxomab will consist of an initial dose of 10µg given intraoperatively as in intraperitoneal bolus and of four postoperative ascending doses.

Drug: Catumaxomab

10 µg intraoperative and 4 ascending doses (10, 20, 50 and 150 µg) on day 7, 10, 13 and 16

Other Name: Removab

Drug: catumaxomab

10 µg intraoperatively and 4 ascending doses: 10, 20, 50 and 150 µg

Other Name: Removab

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00464893

Locations

Austria

Innsbruck, Austria
Germany

Hamburg, Berlin, Heidelberg, Köln, Halle, Germany
Spain

Terrassa, Spain
United Kingdom

Nottingham, United Kingdom

Sponsors and Collaborators

Fresenius Biotech GmbH

Investigators

Principal Investigator:

Carsten Bokemeyer, Prof MD

University Clinic of Hamburg-Eppendorf; 20246 Hamburg / Germany

More Information

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.

Ruf P, Lindhofer H. Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. Blood. 2001 Oct 15;98(8):2526-34.

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.

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.

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.

Responsible Party:	Fresenius Biotech GmbH
ClinicalTrials.gov Identifier:	NCT00464893 History of Changes
Other Study ID Numbers:	IP-CAT-GC-03, EudraCT-Nr.:2006-002727-16
Study First Received:	April 23, 2007
Last Updated:	October 2, 2012
Health Authority:	Germany: Paul-Ehrlich-Institut

Keywords provided by Fresenius Biotech GmbH:

gastric cancer
catumaxomab
neoadjuvant chemotherapy

phase II
interoperative
trifunctional antibody

Additional relevant MeSH terms:

Adenocarcinoma
Adenocarcinoma, Mucinous
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Gastrointestinal Neoplasms

Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013