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

NCT01985893 | Withdrawn Phase 2

• 1 other identifier: BNGO/01 THOR
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Keywords

Metastatic; breast; cancer

Outcome Measures

Primary Outcomes (1)

• 6 month progression-free-survival-rate (PFS6)

  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".

  6 months - from the date of randomization

Secondary Outcomes (1)

• Progression free survival (PFS)

  the complete duration of the study (up to 72 months)

Study Arms (2)

Lapatinib plus trastuzumab

OTHER

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

Lapatinib plus Capecitabine

OTHER

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

Interventions

Lapatinib plus trastuzumab DRUG

Comparison of the safety and efficacy of lapatinib plus trastuzumab and lapatinib plus capecitabine.

Also known as: Tyverb plus Herceptin

Lapatinib plus Capecitabine; Lapatinib plus trastuzumab

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Histologically confirmed and metastatic breast cancer.
• Hormone receptor-negative patients
• HER2-positive tumours with 3+ intensity on IHC staining for HER2 or amplification of the HER2 gene on ISH.
• Patients must have measurable metastatic disease by RECIST v1.1 with radiologic scans within 28 days of study registration.
• 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.
• Prior chemotherapy with anthracyclines and taxanes (unless clinically contraindicated, which must have been documented).
• 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

You may not qualify if:

• 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.
• Hormone receptor-positive patients
• Prior treatment with lapatinib within the last 6 months.
• More than 2 lines of trastuzumab-based treatment for advanced disease.
• 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.
• 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)
• 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)
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Hypersensitivity to trastuzumab, murine proteins or to any of the excipients.
• Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.

Sponsors & Collaborators

• Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.: lead
• OnkoDataMed GmbH: collaborator

Study Sites (17)

Charite Campus Mitte II. Medizinische Klinik Hämatologie und Onkologie

Berlin, 10117, Germany

Location

Gynäkologische Praxis Dr. Jörg Schilling

Berlin, 10317, Germany

Location

MediOnko Institut GbR Dr. Klare

Berlin, 10367, Germany

Location

Gynäkologische Praxis Dr. Ruhmland

Berlin, 12683, Germany

Location

Gynäkologische Gemeinschaftspraxis Morack/Letschert

Berlin, 13156, Germany

Location

Gynäkologische Praxis Dr. Jungberg

Chemnitz, 09117, Germany

Location

UK, Frauenheilk. u. Geburtsklinik Prof. Dr. med. Pauline Wimberger

Dresden, 01307, Germany

Location

Kliniken Essen-Mitte PD Dr. Kümmel

Essen, 45136, Germany

Location

Gynäkologische Praxis Dr. Heinrich

Fürstenwalde, 15517, Germany

Location

Gynäkologische Praxis Dr. Busch

Mühlhausen, 99974, Germany

Location

Gemeinschaftspraxis "Gynäkologie Arabella" Dr. Prechtl

München, 81925, Germany

Location

Praxis für Innere Medizin Dr. Uhlig

Naunhof, 14683, Germany

Location

Gynäkologische Praxis Dr. Guth

Plauen, 08525, Germany

Location

Gynäkologische Praxis Dr. Dietz

Salzgitter, 38226, Germany

Location

g.sund Kompetenzzentrum Dr. Hielscher

Stralsund, 18435, Germany

Location

Asklepios Kliniken Weißenfels Dr. Lampe

Weißenfels, 06667, Germany

Location

Gynäkologische Praxis Dr. Guido Augustinus Süttmann

Wunstorf, 31515, Germany

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dirk Elling, Professor

  Frauenklinik, Sana Klinikum Lichtenberg, Fanningerstr. 32, D-10365 Berlin, Germany

  STUDY CHAIR

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: November 10, 2013
• First Posted: November 15, 2013
• Study Start: September 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: January 14, 2016

Record last verified: 2016-01

Locations

DE (17)