Phase II Study With Catumaxomab in Patients With Gastric Cancer After Neoadjuvant CTx and Curative Resection

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00464893
• Other study ID #: IP-CAT-GC-03
• Secondary ID: EudraCT-Nr.:2006
• Status: Completed
• Phase: Phase 2
• First received: April 23, 2007
• Last updated: December 3, 2013
• Start date: April 2007
• Est. completion date: April 2013

Study information

• Verified date: December 2013
• Source: Neovii Biotech
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: April 2013
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Adenocarcinoma
• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Catumaxomab
10 µg intraoperative and 4 ascending doses (10, 20, 50 and 150 µg) on day 7, 10, 13 and 16
• catumaxomab
10 µg intraoperatively and 4 ascending doses: 10, 20, 50 and 150 µg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Neovii Biotech

Countries where clinical trial is conducted

Austria,  Germany,  Spain,  United Kingdom, 

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