Safety and Tolerability Study of Claudiximab in Patients With Advanced Gastroesophageal Cancer

Solid Tumors Clinical Trial

Official title:

Clinical First-in-human Single-dose Escalation Study Evaluating the Safety and Tolerability of Claudiximab (iMAB-362) in Hospitalized Patients With Advanced Gastroesophageal Cancer. A Multi-center, Phase I, Open-label, i.v. Infusion Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00909025
• Other study ID #: GM-IMAB-001
• Status: Completed
• Phase: Phase 1
• First received: May 18, 2009
• Last updated: June 30, 2017
• Start date: May 2009
• Est. completion date: May 2010

Study information

• Verified date: October 2012
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Claudiximab is a monoclonal antibody specific for gastric and gastroesophageal adenocarcinomas. Preclinically, claudiximab was shown to inhibit tumor growth and to kill cancer cells by indirect (complement-dependent cytoxicity, antibody-dependent cellular cytotoxicity) and direct mechanisms (antiproliferative and proapoptotic effects). The aim of this phase I study is to establish safety, toxicity and maximal tolerable dose of a single infusion of claudiximab in patients suffering from relapsing, advanced gastroesophageal and gastric adenocarcinoma

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Metastatic, refractory or recurrent disease of advanced gastroesophageal cancer (adenocarcinoma) proven by histology

• CLDN18.2 expression confirmed by immunohistochemistry

• Prior standard chemotherapy containing a fluoropyrimidine, a platinum compound and/or epirubicine, and - if clinically appropriate - docetaxel

• At least 1 measurable site of the disease according RECIST criteria (CT-scans or MRT not older than 6 weeks before study entry)

• Age = 18 years

• ECOG performance status (PS) 0-1 or Karnofsky Index 70-100%

• Life expectancy > 3 months

• Platelet count = 100,000/mm³

• Hemoglobin = 10 g/dl

• INR < 1.5

• Bilirubin normal

• AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)

• Creatinine < 1.5 x ULN

Exclusion Criteria:

• Pregnancy or breastfeeding

• Prior allergic reaction or intolerance to a monoclonal antibody

• Prior inclusion in the present study

• Less than 3 weeks since prior anti-tumor or radiation therapy

• Other investigational agents or devices concurrently or within 4 weeks prior to this study

• Other concurrent anticancer therapies

• History of positive test for human immunodeficiency virus (HIV) antibody

• Known Hepatitis.

• Uncontrolled or severe illness.

• Concurrent administration of anticoagulation agents with vitamin K antagonists

• Concurrent administration of therapeutic doses of heparin (prophylactic doses are acceptable)

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Claudiximab
Patients receive Claudiximab as intravenous infusion over 2 hours on day 1. Cohorts of 3-6 patients receive escalating doses of Claudiximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no dose-limiting toxicity (DLT) is diagnosed in 3 patients or no more than 1 out of 6 patients exhibits a DLT. After completion of study treatment, patients are followed for 4 weeks.

Locations

Country	Name	City	State
Germany	Universitätsklinikum Essen, Innere Klinik (Tumorforschung)	Essen
Germany	Universität Heidelberg, Nationales Centrum für Tumorerkrankungen (NCT)	Heidelberg
Germany	Johannes Gutenberg Universität, 1.Med Klinik und Poliklinik	Mainz
Germany	Klinikum Rechts-der-Isar, III.Medizinische Klinik und Poliklinik	München
Latvia	Piejuras Hospital	Liepaja
Latvia	Pauls Stradins University	Riga

Sponsors (1)

Lead Sponsor	Collaborator
Ganymed Pharmaceuticals GmbH

Countries where clinical trial is conducted

Germany,  Latvia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of maximum tolerated dose of claudiximab (Phase I: toxicities as assessed by NCI CTCAE version 3.0)		Four weeks
Secondary	Determination of the safety profile		Four weeks
Secondary	Pharmacokinetic evaluation		Four weeks
Secondary	Overall tumor response as assessed by RECIST		Four weeks
Secondary	Evaluation of immunogenicity		Four weeks
Secondary	Determination of antitumoral efficacy		Four weeks