Clinical trial NCT00909025: Safety and Tolerability Study of Claudiximab in Patients With Advanced Gastroesophageal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2009-05-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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


Eligibility criteria: 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)

Primary outcomes:
measure: Determination of maximum tolerated dose of claudiximab (Phase I: toxicities as assessed by NCI CTCAE version 3.0)
timeFrame: Four weeks
Secondary outcomes:
measure: Determination of the safety profile
timeFrame: Four weeks
measure: Pharmacokinetic evaluation
timeFrame: Four weeks
measure: Overall tumor response as assessed by RECIST
timeFrame: Four weeks
measure: Evaluation of immunogenicity
timeFrame: Four weeks
measure: Determination of antitumoral efficacy
timeFrame: Four weeks
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Innere Klinik (Tumorforschung)
city: Heidelberg
country: Germany
facility: Universität Heidelberg, Nationales Centrum für Tumorerkrankungen (NCT)
city: Mainz
country: Germany
facility: Johannes Gutenberg Universität, 1.Med Klinik und Poliklinik
city: München
country: Germany
facility: Klinikum Rechts-der-Isar, III.Medizinische Klinik und Poliklinik
city: Liepaja
country: Latvia
facility: Piejuras Hospital
city: Riga
country: Latvia
facility: Pauls Stradins University
Study officials:
affiliation: Innere Klinik (Tumorforschung) Universitätsklinikum Essen Hufelandstr. 55 45122 Essen, GERMANY
name: Martin Schuler, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sahin U, Schuler M, Richly H, Bauer S, Krilova A, Dechow T, Jerling M, Utsch M, Rohde C, Dhaene K, Huber C, Tureci O. A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer. Eur J Cancer. 2018 Sep;100:17-26. doi: 10.1016/j.ejca.2018.05.007. Epub 2018 Jun 21.