TrasGEX™: Dose Escalation Study

• ClinicalTrials.gov Identifier: NCT01409343
• Recruitment Status: Completed
• First Posted: August 4, 2011
• Last Update Posted: December 20, 2013
• Sponsor: Glycotope GmbH
• Collaborator: Glycotope Biotechnology GmbH
• Information provided by: Glycotope GmbH

Study Description

Brief Summary:

This is a prospective, open label, multicenter study evaluating the safety, tolerability and pharmacokinetics of TrasGEX™ after intravenous administration in patients with HER-2 positive cancers. The effect of TrasGEX™ on the development of anti-drug antibodies and on tumour response will also be evaluated.

Condition or disease	Intervention/treatment	Phase
Solid Tumors	Drug: TrasGEX™	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Dose-Escalation and Pharmacokinetic Study of TrasGEX™ in Patients With Locally Advanced or Metastatic HER-2-positive Cancer
• Study Start Date: July 2011
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. optimal dose and regimen of TrasGEX™ [ Time Frame: up to at least 8 weeks after the first TrasGEX™ administration ]
   The primary objective of this first-in-man study is to determine the optimal dose and regimen of TrasGEX™ in patients with locally advanced or metastatic human epidermal growth factor receptor-2 (HER-2)-positive cancer. The recommended phase II dose needs to have an acceptable safety profile and provides evidence for efficacy based on clinical observations or the pharmacokinetic profile.

Secondary Outcome Measures :

1. To determine preliminary evidence of activity [ Time Frame: approx. every 8 weeks ]
   CT or MRI imaging will be performed. Assessment of tumor response (SD, PR, CR. PD) will be performed following a modified version of the revised RECIST guidelines, version 1.1. Basically, patients will receive treatment with TrasGEX™ until progression of disease and/or unacceptable toxicities are observed.
2. safety and tolerability of TrasGEX™ [ Time Frame: until 4 weeks after the last treatment with TrasGEX™ ]
   To assess the safety and tolerability of TrasGEX™ in patients with advanced and/or metastatic HER-2-positive cancer at various dose levels considering observed adverse events, laboratory values, vital signs, ECOG performance status and physical examination.
3. To assess the pharmacokinetic (PK) profile of TrasGEX™ (part I) [ Time Frame: prior to 1st infusion until the end of 5th infusion ]
   c(max): to determine the PK profile samples will be taken before the first infusion and up to 24 h after after infusion, followed by weekly samples for the first infusion and samples immediately before and after infusion for the following infusions
4. To assess the pharmacokinetic (PK) profile of TrasGEX™ (part II) [ Time Frame: prior to 1st infusion until the end of 5th infusion ]
   t(1/2): to determine the PK profile samples will be taken before the first infusion and up to 24 h after after infusion, followed by weekly samples for the first infusion and samples immediately before and after infusion for the following infusions

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Main Inclusion Criteria:

1. Signed written informed consent granted prior to initiation of any study-specific procedures;
2. Male or female patients of ≥18 years of age;
3. ERBB2 (HER-2) gene amplification or ERBB2 overexpression
4. Histologically or cytologically confirmed cancer, either locally advanced or metastatic;
5. No anti-tumor therapy of proven benefit available at study enrollment;
6. Life expectancy of >=3 months;
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) <=2;
8. Male or female patients of child-producing potential must agree to use contraceptive measures or oral contraception during the study and for 28 days after the last dose of TrasGEX™;
9. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of TrasGEX™;

and

Main Exclusion Criteria:

1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks of the first dose of TrasGEX™;
2. Major surgery within four weeks of the first dose of TrasGEX™;
3. Newly diagnosed brain metastases, metastases that have been documented to be stable for <3 months, or metastases for which systemic corticosteroids are required;
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition as TrasGEX™;
5. History of myocardial infarction within 12 months of the administration of the first dose of TrasGEX™;
6. History of congestive heart failure defined as Class II to IV per New York Heart Association classification within 12 months of the administration of the first dose of TrasGEX™;
7. Left ventricular ejection fraction <50%;
8. Previous malignancy other than the current diagnosis within 5 years of the first dose of TrasGEX™;
9. Pregnancy or lactation; and
10. Concurrent uncontrolled significant illness

Contacts and Locations

Locations

Austria

Glycotope Investigational Site

Graz, Austria, 8036

Glycotope Investigational Site

Innsbruck, Austria, 6020

Sponsors and Collaborators

Glycotope GmbH

Glycotope Biotechnology GmbH

Investigators

• Study Director: Glycotope GmbH; Glycotope GmbH

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fiedler W, Stoeger H, Perotti A, Gastl G, Weidmann J, Dietrich B, Baumeister H, Danielczyk A, Goletz S, Salzberg M, De Dosso S. Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours. ESMO Open. 2018 Jun 23;3(4):e000381. doi: 10.1136/esmoopen-2018-000381. eCollection 2018.

• Responsible Party: Glycotope GmbH, Study Director, Glycotope GmbH
• ClinicalTrials.gov Identifier: NCT01409343
• Other Study ID Numbers: GEXMab73101
• First Posted: August 4, 2011
• Last Update Posted: December 20, 2013
• Last Verified: December 2013

Keywords provided by Glycotope GmbH:

advanced solid cancers; metastatic solid cancers