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Safety and Efficacy of Lapatinib Plus Trastuzumab or Lapatinib Plus Capecitabine in Metastatic Breast Cancer (THOR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.
Sponsor:
Collaborator:
OnkoDataMed GmbH
Information provided by (Responsible Party):
Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.
ClinicalTrials.gov Identifier:
NCT01985893
First received: November 10, 2013
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to estimate the clinical benefit of lapatinib plus trastuzumab compared to lapatinib plus capecitabine as measured by investigator-assessed progression-free survival, tumour response and overall survival.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Lapatinib plus trastuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised, Open-label Phase II Study to Compare the Safety and Efficacy of Lapatinib Plus Trastuzumab or Lapatinib Plus Capecitabine in Trastuzumab-resistant HER2-overexpressing Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.:

Primary Outcome Measures:
  • 6 month progression-free-survival-rate (PFS6) [ Time Frame: 6 months - from the date of randomization ] [ Designated as safety issue: No ]

    The primary outcome measure for this study is:

    • The 6-month PFS-rate (PFS6) The 6-month PFS-rate (PFS6) will be the number of patients without disease progression or death within 6 months from the date of randomization, divided by the number of patients in the respective analysis population. For the purpose of the analysis patients who are lost to follow-up or deceased in at or before 6 months after randomization will be counted as "disease progression".



Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: the complete duration of the study (up to 72 months) ] [ Designated as safety issue: No ]
    Progression free survival (PFS), defined as the time from randomisation to disease progression (as assessed by the site radiologist and/or investigator, using the Response Evaluation Criteria in Solid Tumours (RECIST1.1)) or death on study from any cause (defined as death within 30 days of the last study treatment), whichever occurs first. Data for patients who experienced no progress or who are lost to follow-up will be treated as censored on the last date the patient was known to be progression free.


Estimated Enrollment: 100
Study Start Date: September 2013
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Lapatinib plus trastuzumab
Drug intervention: Lapatinib IMP, Trastuzumab on prescription. Lapatinib 1000 mg p.o. once daily for 21 days. Trastuzumab i.v. infusion 8 mg/kg loading dose; 6 mg/kg on Day 1 of each subsequent 3 weekly cycle.
Drug: Lapatinib plus trastuzumab
Comparison of the safety and efficacy of lapatinib plus trastuzumab and lapatinib plus capecitabine.
Other Name: Tyverb plus Herceptin
Lapatinib plus Capecitabine
Drug intervention: Lapatinib and Capecitabine on prescription. Lapatinib 1250 mg p.o. once daily. Capecitabine 2000 mg/m2 p.o. in two divided doses on days 1 to 14 of a 21 day cycle.
Drug: Lapatinib plus trastuzumab
Comparison of the safety and efficacy of lapatinib plus trastuzumab and lapatinib plus capecitabine.
Other Name: Tyverb plus Herceptin

Detailed Description:

This is an open-label, randomized, explorative phase II trial of lapatinib plus trastuzumab or lapatinib plus capecitabine in patients with HER2 overexpressing metastatic breast cancer. The trial is designed to obtain some evidence wether chemotherapy-free combined HER2-directed therapy with lapatinib and trastuzumab provides a similar efficacy as the established combination of lapatinib with capecitabine and a more favourable toxicity profile. This study will also assess the relationship between the anticipated anti-tumour activity of the treatment regimens and biological characteristics of subjects' tumour at baseline.

The purpose of this study is to estimate the clinical benefit of lapatinib plus trastuzumab compared to lapatinib plus capecitabine as measured by investigator-assessed progression-free survival, tumour response and overall survival.

The purpose of this study ist further

  • to characterize the safety and tolerability of lapatinib plus trastuzumab in this population.
  • to identify predictors of sensitivity to lapatinib and trastuzumab therapy. and
  • to compare the differences in health-related quality of life (HRQL) and pain symptoms for patients by treatment assignment.
  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed and metastatic breast cancer.
  2. Hormone receptor-negative patients
  3. HER2-positive tumours with 3+ intensity on IHC staining for HER2 or amplification of the HER2 gene on ISH.
  4. Patients must have measurable metastatic disease by RECIST v1.1 with radiologic scans within 28 days of study registration.
  5. Prior anti-HER based therapy:

    • Received at least 1 but no more than 2 prior anti-HER2 based regimens for metastatic disease.
    • Prior treatment with trastuzumab-DM1 (TDM1) is allowed (T-DM1 represents one line of anti-HER2 and one line of chemotherapy).
    • Radiological evidence of confirmed progressive disease per RECIST while receiving trastuzumab as a single agent or in combination with chemotherapy for at least 6 weeks either as first line or second line therapy, for an interval of at least 6 weeks at any time.
    • Prior treatment with Lapatinib is permitted provided that at least 6 month have elapsed since the last dose.
  6. Prior chemotherapy with anthracyclines and taxanes (unless clinically contraindicated, which must have been documented).
  7. Patients must have the following laboratory values:

    • Absolute Neutrophil count (ANC) ≥ 1.5 x 109/L
    • Platelets ≥ 100 x 109/L
    • AST and ALT ≤ 2.5 x ULN
    • Bilirubin level ≤ 1.25 X ULN
    • Serum creatinine < 1.5 X ULN or calculated creatinine clearance ≥ 40ml/min
  8. Normal cardiac function with a left ventricular ejection fraction of at least 50% (as assessed by quantitative echocardiogram)
  9. ECOG performance status 0-1
  10. Age ≥ 18 years
  11. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had hysterectomy, a bilateral oophorectomy, bilateral tubular ligation or is post-menopausal (total cessation of menses for ≥ 1 year; if the patient is of childbearing potential, she must have a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception (for example, intrauterine device [IUD], birth control pills unless clinically contraindicated, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product.
  12. Written informed consent prior to admission to this study.

Exclusion Criteria:

  1. Patients with confirmed brain metastases or a history of primary central nervous system tumours or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases. Patients with treated brain metastases that are asymptomatic and have been clinically stable for 3 months will be eligible for protocol participation.
  2. Hormone receptor-positive patients
  3. Prior treatment with lapatinib within the last 6 months.
  4. More than 2 lines of trastuzumab-based treatment for advanced disease.
  5. Significant cardiovascular disease, such as

    • History of myocardial infarction, acute coronary syndromes (including unstable angina), or history of coronary angioplasty/stenting/bypass grafting within past 6 months.
    • History of symptomatic congestive heart failure (CHF) New York Heart Association (NYHA) Classes II-IV or LVEF <50% by ECHO.
    • Severe cardiac arrhythmia requiring medication or severe conduction abnormalities.
    • Poorly controlled hypertension (resting diastolic blood pressure >100 mmHg)
    • Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, or cardiomyopathy.
  6. QTc prolongation defined as a QTc interval > 460 msec or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate < 50 beats/min)
  7. Subjects who have current active hepatic or biliary disease or severe hepatic impairment (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
  8. Malabsorption syndrome or other condition that would interfere with enteral absorption
  9. Hypersensitivity to trastuzumab, murine proteins or to any of the excipients.
  10. Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
  11. History of severe and unexpected reactions to fluoropyrimidine therapy.
  12. Hypersensitivity to capecitabine or to any of the excipients or fluorouracil.
  13. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
  14. Severe leucopenia, neutropenia or thrombocytopenia.
  15. Severe renal impairment (creatinine clearance < 40 ml/min.).
  16. Treatment with sorivudine or its chemically related analogues, such as brivudine.
  17. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
  18. Contraindications to any of the medicinal products in the combination regimen.
  19. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
  20. Patients accommodated in a closed institution by authority or court order.
  21. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry.
  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: NCT01985893

Contacts
Contact: Anne-Katrin Ullner +49 3342 42689 10 info@onkodatamed.de

Locations
Germany
MediOnko Institut GbR Dr. Klare Recruiting
Berlin, Germany, 10367
Contact: Peter Klare, MD       studien@medionko.de   
Principal Investigator: Peter Klare, MD         
Sub-Investigator: Steffen Gläser, MD         
Gynäkologische Gemeinschaftspraxis Morack/Letschert Recruiting
Berlin, Germany, 13156
Contact: Dörthe Morack, MD       info@onko-gyn-praxis.de   
Principal Investigator: Dörthe Morack, MD         
Sub-Investigator: Christine Letschert         
Gynäkologische Praxis Dr. Jörg Schilling Recruiting
Berlin, Germany, 10317
Contact: Jörg Schilling, MD       dr.joerg.schilling@t-online.de   
Principal Investigator: Jörg Schilling, MD         
Sub-Investigator: Angelika Till, MD         
Charite Campus Mitte II. Medizinische Klinik Hämatologie und Onkologie Recruiting
Berlin, Germany, 10117
Contact: Jan Eucker, MD       jan.eucker@charite.de   
Principal Investigator: Jan Eucker, MD         
Sub-Investigator: Jan-Piet Habbel, MD         
Gynäkologische Praxis Dr. Ruhmland Recruiting
Berlin, Germany, 12683
Contact: Birgit Ruhmland, MD       info@praxis-ruhmland.de   
Principal Investigator: Birgit Ruhmland, MD         
Sub-Investigator: Sophia Bossenz         
Gynäkologische Praxis Dr. Jungberg Recruiting
Chemnitz, Germany, 09117
Contact: Peter Jungberg, MD       jungberg@arcor.de   
Principal Investigator: Peter Jungberg, MD         
Sub-Investigator: Dagmar Guth, MD         
UK, Frauenheilk. u. Geburtsklinik Prof. Dr. med. Pauline Wimberger Recruiting
Dresden, Germany, 01307
Contact: Pauline Wimberger, MD       pauline.wimberger@uniklinikum-dresden.de   
Principal Investigator: Pauline Wimberger, MD         
Sub-Investigator: Karin Kast, MD         
Kliniken Essen-Mitte PD Dr. Kümmel Recruiting
Essen, Germany, 45136
Contact: Sherko Kümmel, MD       s.kuemmel@kliniken-essen-mitte.de   
Principal Investigator: Sherko Kümmel, MD         
Sub-Investigator: Hanns Schwanke-Theißen, MD         
Gynäkologische Praxis Dr. Heinrich Recruiting
Fürstenwalde, Germany, 15517
Contact: Georg Heinrich, MD       drheinrich@praxis-heinrich.de   
Principal Investigator: Georg Heinrich, MD         
Sub-Investigator: Marek Budner, MD         
Gynäkologische Praxis Dr. Busch Recruiting
Mühlhausen, Germany, 99974
Contact: Steffi Busch, MD       dr.steffi.busch@telemed.de   
Principal Investigator: Steffi Busch, MD         
Sub-Investigator: Nadine Mosebach, MD         
Gemeinschaftspraxis "Gynäkologie Arabella" Dr. Prechtl Recruiting
München, Germany, 81925
Contact: Anita Prechtl, MD       praxis@gynaekologie-arabella.de   
Principal Investigator: Anita Prechtl, MD         
Sub-Investigator: Daniel Sattler, MD         
Praxis für Innere Medizin Dr. Uhlig Recruiting
Naunhof, Germany, 14683
Contact: Jens Uhlig, MD       dr.uhlig@onkologie-muldental.de   
Principal Investigator: Jens Uhlig, MD         
Sub-Investigator: Bettina Peuser, MD         
Gynäkologische Praxis Dr. Guth Recruiting
Plauen, Germany, 08525
Contact: Dagmar Guth, MD       dr.guth@online.de   
Principal Investigator: Dagmar Guth, MD         
Sub-Investigator: Peter Jungberg, MD         
Gynäkologische Praxis Dr. Dietz Recruiting
Salzgitter, Germany, 38226
Contact: Wolfgang Dietz, MD       witte-dietz@t-online.de   
Principal Investigator: Wolfgang Dietz, MD         
Sub-Investigator: Gudrun Witte-Dietz         
g.sund Kompetenzzentrum Dr. Hielscher Recruiting
Stralsund, Germany, 18435
Contact: Carsten Hielscher, MD       hielscher@gyn-stralsund.de   
Principal Investigator: Carsten Hielscher, MD         
Sub-Investigator: Frank Ruhland, MD         
Asklepios Kliniken Weißenfels Dr. Lampe Recruiting
Weißenfels, Germany, 06667
Contact: Dieter Lampe, MD       d.lampe@asklepios.com   
Principal Investigator: Dieter Lampe, MD         
Sub-Investigator: Ute Wirth         
Gynäkologische Praxis Dr. Guido Augustinus Süttmann Recruiting
Wunstorf, Germany, 31515
Contact: Guido A. Süttmann, MD       info@suettmann-makowski.de   
Principal Investigator: Guido Augustinus Süttmann, MD         
Sub-Investigator: Lars Makowski, MD         
Sponsors and Collaborators
Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.
OnkoDataMed GmbH
Investigators
Study Chair: Dirk Elling, Professor Frauenklinik, Sana Klinikum Lichtenberg, Fanningerstr. 32, D-10365 Berlin, Germany
  More Information

No publications provided

Responsible Party: Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.
ClinicalTrials.gov Identifier: NCT01985893     History of Changes
Other Study ID Numbers: BNGO/01 THOR
Study First Received: November 10, 2013
Last Updated: August 29, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.:
Metastatic
breast
cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Lapatinib
Trastuzumab
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014