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

Sponsor
National Center for Tumor Diseases, Heidelberg (Other)
Overall Status
Terminated
CT.gov ID
NCT01145404
Collaborator
(none)
76
Enrollment
16
Locations
2
Arms
40
Duration (Months)
4.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
76 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Jun 1, 2010
Actual Primary Completion Date :
Feb 1, 2013
Actual Study Completion Date :
Oct 1, 2013

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • Tyverb, Xeloda

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective response rate (ORR) [about 10 month (until progression)]

      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

    1. Time to tumor progression [about 10 month (until tumor progression)]

      Time to tumor progression

    2. Overall survival [about 16 month (6 month after progression)]

      Overall survival

    3. Safety and tolerability of study treatment (for parameters see description) [about 10 month (until progression)]

      recording of AEs/SAEs, vital signs, ECG, LVEF, physical exams, lab values

    4. Biomarker analysis [1 month (during screening period)]

      the definition of biomarkers that are associated with response or resistance to treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 CHARITÉ CAMPUS, VIRCHOW-KLINIKUM, UNIVERSITÄTSMEDIZIN BERLIN, Centrum 14, Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie Berlin Germany 13353
    2 Evangelisches Krankenhaus Bielefeld gGmbH, Klinik für Innere Medizin, Hämatologie/Onkologie und Palliativmedizin Bielefeld Germany 33611
    3 Medizinische Uniklinik, Knappschaftskrankenhaus Bochum Bochum Germany 44892
    4 Evangelische Kliniken Bonn gGmbH, Johanniter-Krankenhaus Bonn Germany 53113
    5 Städtisches Klinikum Braunschweig gGmbH Braunschweig Germany 38114
    6 Kliniken Essen Mitte, Department of Medical Oncology and Hematology Essen Germany 45136
    7 Klinikum Esslingen, Klinik für Allgemeine Innere Medizin, Onkologie und Gastroenterologie Esslingen Germany 73730
    8 Krankenhaus Nord West Frankfurt Germany 60488
    9 Universitätsklinikum Halle, Klinik für Innere Medizin IV Halle Germany 06120
    10 OncoResearch Lerchenfeld UG Hamburg Germany 22081
    11 Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie, Endokrinologie Hannover Germany 30625
    12 NCT Heidelberg Heidelberg Germany 69120
    13 I. Med. Klinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany 55101
    14 Universitätsklinikum Gießen und Marburg GmbH Marburg Germany 35043
    15 Klinikum rechts der Isar München Germany 81675
    16 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Center for Tumor Diseases, Heidelberg
    ClinicalTrials.gov Identifier:
    NCT01145404
    Other Study ID Numbers:
    • NCT-2008-11-01-1015
    First Posted:
    Jun 16, 2010
    Last Update Posted:
    Jul 2, 2014
    Last Verified:
    Jul 1, 2014
    Keywords provided by National Center for Tumor Diseases, Heidelberg
    Her2 Gastro Gastric Esophageal Cancer
    Additional relevant MeSH terms:
    Esophageal Neoplasms
    Capecitabine
    Lapatinib

    Study Results

    No Results Posted as of Jul 2, 2014