Trial of Lapatinib Versus Lapatinib With Capecitabine in Her2+ Metastatic Gastro-Esophageal Cancer

NCT01145404 | Terminated Phase 2 DMC

• 1 other identifier: NCT-2008-11-01-1015
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 16

Brief Summary

Combining Erb inhibitors, such lapatinib, and TS inhibitors, such as capecitabine, may be a beneficial contribution to current treatment paradigms since preclinical data suggest that lapatinib alone can decrease TS mRNA and is synergistic with capecitabine in some cell lines, which may contribute to clinical benefit. The study described in this protocol has been designed to establish the anti-tumor activity of Lapatinib with or without capecitabine in the treatment of Her2 overexpressing metastatic gastric- and gastro-esophageal cancer, and to search for molecular correlates that may be associated with response to this compound. The majority of patients with metastatic gastric and gastro-esophageal cancer undergo first-line combined chemotherapy (e.g. platin derivates and fluoropyrimidines, sometimes combined to a taxane), but the role of second-line chemotherapy has not yet been defined. Therefore, progression during or shortly after first-line chemotherapy is a medical condition no standard medical approach exists. The overexpression of EGFR and Her2 in gastric and gastroesophageal cancer make these indications prime candidate for treatment with the dual ErbB1/2 tyrosine kinase inhibitor (TKI) Lapatinib.

Conditions

GastroEsophageal Cancer

Keywords

Her2 Gastro Gastric Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Objective response rate (ORR, complete and partial remission according to RECIST criteria \- all to be confirmed by at least two consecutive tumor response assessments within no shorter than 4 weeks)

  about 10 month (until progression)

Secondary Outcomes (4)

• Time to tumor progression

  about 10 month (until tumor progression)

• Overall survival

  about 16 month (6 month after progression)

• Safety and tolerability of study treatment (for parameters see description)

  about 10 month (until progression)

• Biomarker analysis

  1 month (during screening period)

Study Arms (2)

Arm A: Lapatinib

EXPERIMENTAL

Lapatinib (Tyverb) po 1500mg daily d1-21, new cycle will be started on day 22 until progression.

Drug: Lapatinib

Arm B

EXPERIMENTAL

Lapatinib po 1250mg daily d1-21; new cycle will be started on day 22 until progression

Drug: Lapatinib plus capecitabine

Interventions

Lapatinib DRUG

Lapatinib (Tyverb) po 1500mg daily d1-21, new cycle will be started on day 22 until progression.

Also known as: Tyverb

Arm A: Lapatinib

Lapatinib plus capecitabine DRUG

Lapatinib po 1250mg daily d1-21; new cycle will be started on day 22 until progression

Also known as: Tyverb, Xeloda

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the stomach, including adenocarcinoma of the gastroesophageal junction and esophagus
• Metastatic disease
• Measurable disease (according to RECIST criteria)
• At least one prior chemotherapy for metastatic disease with progression during or no later than 6 months after last administration of chemotherapy. Chemotherapy must have contained a platinum compound (cisplatin or oxaliplatin)
• Her2 overexpression measured by FISH (amplification or increased gene copy number). Immunohistochemistry (ICH) 3+ can be included in case of an uncertain FISH test.
• Patient willing to allow for biomarker analyses on his tumor tissue.
• Written informed consent given prior to any protocol specific procedures according to the local regulatory requirements
• Age \>= 18 years
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) \<= 2
• Life expectancy \> 3 months
• Adequate hematological, hepatic and renal function defined by: Hematology: Neutrophils \>1.5x109/L; Platelets \>100x109/L; Hemoglobin \>8g/dL Hepatic function: Total bilirubin \<=1.5xULN; ASAT (SGOT) and ALAT (SGPT) \<= 2.5xULN; Alkaline phosphatase \<5xULN. Renal function: The calculated creatinine clearance should be .60 mL/min
• Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the local Principal Investigator. A list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided in: Cytochrome P-450 Enzymes and Drug metabolism. In: Lacy CF, Armstrong LL, Goldman MP, Lance LL eds. Drug Information Handbook 8TH ed. Hudson, OH; LexiComp Inc. 2000: 1364-1371
• Able to swallow and retain oral medication
• Negative pregnancy test (urine or serum) within 28 days prior to randomization for all women of childbearing potential (has to be verified within 7 days prior to randomization and during the study according the judgement of the investigator)
• Willingness to perform double-barrier contraception during study and 6 months after end of treatment

You may not qualify if:

• Previous non curatively treated malignant disease other than the current gastroesophageal cancer with a disease-free survival of less than 5 years
• History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
• History of active Hepatitis B or C or history of an HIV infection
• Active uncontrolled infection
• Treatment within any other clinical trial parallel to the treatment phase of the current study within 30 days prior to randomisation.
• Concurrent treatment with any other anti-cancer drug. Presence of other medication that may interfere with study treatment or the action of the investigational product or confuse the assessment of study results
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or to any excipients
• History of allergic reactions attributed to compounds of similar chemical composition to capecitabine, fluorouracil or to any excipients
• Known DPD deficiency
• Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors
• Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Active cardiac disease, defined as:
• History of uncontrolled or symptomatic angina
• History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation
• Myocardial infarction \< 6 months from randomization

Sponsors & Collaborators

• National Center for Tumor Diseases, Heidelberg: lead

Study Sites (16)

CHARITÉ CAMPUS, VIRCHOW-KLINIKUM, UNIVERSITÄTSMEDIZIN BERLIN, Centrum 14, Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie

Berlin, 13353, Germany

Location

Evangelisches Krankenhaus Bielefeld gGmbH, Klinik für Innere Medizin, Hämatologie/Onkologie und Palliativmedizin

Bielefeld, 33611, Germany

Location

Medizinische Uniklinik, Knappschaftskrankenhaus Bochum

Bochum, 44892, Germany

Location

Evangelische Kliniken Bonn gGmbH, Johanniter-Krankenhaus

Bonn, 53113, Germany

Location

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, 38114, Germany

Location

Kliniken Essen Mitte, Department of Medical Oncology and Hematology

Essen, 45136, Germany

Location

Klinikum Esslingen, Klinik für Allgemeine Innere Medizin, Onkologie und Gastroenterologie

Esslingen am Neckar, 73730, Germany

Location

Krankenhaus Nord West

Frankfurt, 60488, Germany

Location

Universitätsklinikum Halle, Klinik für Innere Medizin IV

Halle, 06120, Germany

Location

OncoResearch Lerchenfeld UG

Hamburg, 22081, Germany

Location

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie, Endokrinologie

Hanover, 30625, Germany

Location

NCT Heidelberg

Heidelberg, 69120, Germany

Location

I. Med. Klinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität

Mainz, 55101, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Marburg, 35043, Germany

Location

Klinikum rechts der Isar

München, 81675, Germany

Location

Klinikum Regensburg, Klinik und Poliklinik für Innere Medizin I

Regensburg, 93042, Germany

Location

Related Publications (1)

• Lorenzen S, Riera Knorrenschild J, Haag GM, Pohl M, Thuss-Patience P, Bassermann F, Helbig U, Weissinger F, Schnoy E, Becker K, Stocker G, Ruschoff J, Eisenmenger A, Karapanagiotou-Schenkel I, Lordick F. Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Eur J Cancer. 2015 Mar;51(5):569-76. doi: 10.1016/j.ejca.2015.01.059. Epub 2015 Feb 16.

  PMID: 25694417 DERIVED

MeSH Terms

Interventions

Lapatinib; Capecitabine

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Florian Lordick, MD

  Academic Teaching Hospital Braunschweig

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2010
• First Posted: June 16, 2010
• Study Start: June 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: October 1, 2013
• Last Updated: July 2, 2014

Record last verified: 2014-07

Locations

DE (16)