Solid Tumors
Conditions
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
Interventions
DRUGClaudiximab
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.
Sponsors
Ganymed Pharmaceuticals GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determination of maximum tolerated dose of claudiximab (Phase I: toxicities as assessed by NCI CTCAE version 3.0) | Four weeks |
Secondary
| Measure | Time frame |
|---|---|
| Determination of the safety profile | Four weeks |
| Pharmacokinetic evaluation | Four weeks |
| Overall tumor response as assessed by RECIST | Four weeks |
| Evaluation of immunogenicity | Four weeks |
| Determination of antitumoral efficacy | Four weeks |
Countries
Germany, Latvia
Outcome results
None listed