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

This study has been terminated.
(Changes of SoC for third line therapy resulting in poor recruitment)
Sponsor:
Information provided by (Responsible Party):
National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier:
NCT01145404
First received: May 21, 2010
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
GastroEsophageal Cancer
Drug: Lapatinib
Drug: Lapatinib plus capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Lapatinib Versus Lapatinib With Capecitabine as Second-line Treatment in Her2-Overexpressing Metastatic Gastro-Esophageal Cancer: A Randomized Phase II Trial

Resource links provided by NLM:


Further study details as provided by National Center for Tumor Diseases, Heidelberg:

Primary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: about 10 month (until progression) ] [ Designated as safety issue: No ]

    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)



Secondary Outcome Measures:
  • Time to tumor progression [ Time Frame: about 10 month (until tumor progression) ] [ Designated as safety issue: No ]
    Time to tumor progression

  • Overall survival [ Time Frame: about 16 month (6 month after progression) ] [ Designated as safety issue: No ]
    Overall survival

  • Safety and tolerability of study treatment (for parameters see description) [ Time Frame: about 10 month (until progression) ] [ Designated as safety issue: Yes ]
    recording of AEs/SAEs, vital signs, ECG, LVEF, physical exams, lab values

  • Biomarker analysis [ Time Frame: 1 month (during screening period) ] [ Designated as safety issue: No ]
    the definition of biomarkers that are associated with response or resistance to treatment


Estimated Enrollment: 76
Study Start Date: June 2010
Study Completion Date: October 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Lapatinib
Lapatinib (Tyverb) po 1500mg daily d1-21, new cycle will be started on day 22 until progression.
Drug: Lapatinib
Lapatinib (Tyverb) po 1500mg daily d1-21, new cycle will be started on day 22 until progression.
Other Name: Tyverb
Experimental: Arm B
Lapatinib po 1250mg daily d1-21; new cycle will be started on day 22 until progression
Drug: Lapatinib plus capecitabine
Lapatinib po 1250mg daily d1-21; new cycle will be started on day 22 until progression
Other Name: Tyverb, Xeloda

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Ability to understand and the willingness to sign a written informed consent document
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

  • 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
      • Uncontrolled or symptomatic congestive heart failure (> New York Heart Association score 2)
      • Ejection fraction below the institutional normal limit
      • Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
  • Pregnancy and lactation
  • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01145404

Locations
Germany
CHARITÉ CAMPUS, VIRCHOW-KLINIKUM, UNIVERSITÄTSMEDIZIN BERLIN, Centrum 14, Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie
Berlin, Germany, 13353
Evangelisches Krankenhaus Bielefeld gGmbH, Klinik für Innere Medizin, Hämatologie/Onkologie und Palliativmedizin
Bielefeld, Germany, 33611
Medizinische Uniklinik, Knappschaftskrankenhaus Bochum
Bochum, Germany, 44892
Evangelische Kliniken Bonn gGmbH, Johanniter-Krankenhaus
Bonn, Germany, 53113
Städtisches Klinikum Braunschweig gGmbH
Braunschweig, Germany, 38114
Kliniken Essen Mitte, Department of Medical Oncology and Hematology
Essen, Germany, 45136
Klinikum Esslingen, Klinik für Allgemeine Innere Medizin, Onkologie und Gastroenterologie
Esslingen, Germany, 73730
Krankenhaus Nord West
Frankfurt, Germany, 60488
Universitätsklinikum Halle, Klinik für Innere Medizin IV
Halle, Germany, 06120
OncoResearch Lerchenfeld UG
Hamburg, Germany, 22081
Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie, Endokrinologie
Hannover, Germany, 30625
NCT Heidelberg
Heidelberg, Germany, 69120
I. Med. Klinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität
Mainz, Germany, 55101
Universitätsklinikum Gießen und Marburg GmbH
Marburg, Germany, 35043
Klinikum rechts der Isar
München, Germany, 81675
Klinikum Regensburg, Klinik und Poliklinik für Innere Medizin I
Regensburg, Germany, 93042
Sponsors and Collaborators
National Center for Tumor Diseases, Heidelberg
Investigators
Study Director: Florian Lordick, MD Städtisches Klinikum Braunschweig
  More Information

No publications provided

Responsible Party: National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier: NCT01145404     History of Changes
Other Study ID Numbers: NCT-2008-11-01-1015
Study First Received: May 21, 2010
Last Updated: July 1, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by National Center for Tumor Diseases, Heidelberg:
Her2 Gastro Gastric Esophageal Cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Capecitabine
Lapatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014