Phase II Study With Catumaxomab in Patients With Gastric Cancer After Neoadjuvant CTx and Curative Resection
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 Names:
Drug: catumaxomab
10 µg intraoperatively and 4 ascending doses: 10, 20, 50 and 150 µg
Other Names:
|
Outcome Measures
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 [30 days after last catumaxomab administration]
Secondary Outcome Measures
- frequency, relationship and seriousness of adverse events [30 days after last catumaxomab administration]
- surgical resection rate [after surgery]
- chemotherapeutic response rate [after neoadjuvant CTx]
- overall survival at 3, 6, 9, 12 and 24 month after EOT, defined as the time from study enrolment until death [2 years]
- 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 [2 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
signed and dated informed consent
-
male or female patient at an age of 18 years or older
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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
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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
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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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Innsbruck | Austria | |||
| 2 | Hamburg, Berlin, Heidelberg, Köln, Halle | Germany | |||
| 3 | Terrassa | Spain | |||
| 4 | Nottingham | United Kingdom |
Sponsors and Collaborators
- Neovii Biotech
Investigators
- Principal Investigator: Carsten Bokemeyer, Prof MD, University Clinic of Hamburg-Eppendorf; 20246 Hamburg / Germany
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- Ruf P, Lindhofer H. Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. Blood. 2001 Oct 15;98(8):2526-34.
- 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.
- 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.
- IP-CAT-GC-03
- EudraCT-Nr.:2006-002727-16