Status:

TERMINATED

Continued HER2 Suppression With Lapatinib Plus Trastuzumab Versus Trastuzumab Alone

Lead Sponsor:

Novartis Pharmaceuticals

Conditions:

Cancer

Eligibility:

FEMALE

18+ years

Phase:

PHASE3

Brief Summary

This was a randomized, open-label, multi-center Phase III study evaluating the efficacy and safety of lapatinib in combination with trastuzumab versus trastuzumab alone as continued HER2 suppression t...

Eligibility Criteria

Inclusion

  • Signed the informed consent form (ICF)
  • Female, ≥18 years of age
  • Histologically verified breast cancer with distant metastases (metastatic breast cancer)
  • Documentation of HER2 overexpression or gene amplification in the invasive component of either the primary tumor or metastatic disease site defined as:
  • 3+ by IHC and/or
  • HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization \[FISH, CISH or SISH; \>6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH HER2 gene copies to chromosome 17 signal ratio of ≥2.0\]
  • Completed 12 to 24 weeks of first- or second-line treatment with trastuzumab in combination with chemotherapy
  • Either complete disappearance of all lesions, or persistence of metastatic disease (stable disease) without unequivocal progression or the occurrence of new lesions
  • Documentation of lesion response during the course of therapy received prior to randomization (i.e., improvement or no worsening of tumor burden; the absence of new lesions)
  • Measurable disease is not required for study participation
  • No known or suspected (associated neurological signs and symptoms) brain metastases (including leptomeningeal involvement)
  • Stable brain metastasis (defined as asymptomatic and off steroids ≥3 months) are permitted in subjects on second-line treatment (completed 12-24 weeks of second-line treatment with trastuzumab plus chemotherapy)
  • Baseline of Left Ventricular Ejection Fraction (LVEF) ≥50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA)
  • Completion of screening assessments
  • Have adequate marrow and organ function

Exclusion

  • History of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of completely resected non-melanoma skin cancer (basal or squamous) are eligible
  • Eastern Cooperative Oncology Group (ECOG) Performance Status \>2
  • Concurrent anti-cancer treatment, except anti-hormonal therapy for subjects with hormone receptor positive breast cancer
  • Concurrent treatment with an investigational agent
  • Prior treatment with anti-HER2 therapy, except trastuzumab or lapatinib
  • Concurrent treatment with protocol-defined prohibited medications (refer to protocol for details)
  • Serious cardiac illness or medical condition including but not confined to:
  • Uncontrolled arrhythmias
  • Uncontrolled or symptomatic angina
  • History of congestive heart failure (CHF)
  • Myocardial infarction \<6 months from study entry
  • Acute or current active (requiring anti-viral therapy) hepatic or biliary disease (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
  • Concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent)
  • Women of childbearing potential, including women whose last menstrual period was \<12 months ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during the study treatment period. Adequate contraception includes intra-uterine device, barrier methods with spermicide, or oral contraceptives (unless clinically contraindicated for the subject population or per local practice, refer to protocol for further details)
  • Pregnant or lactating females
  • Any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients that, in the opinion of the Investigator or GSK medical monitor , contra-indicates participation

Key Trial Info

Start Date :

January 20 2010

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

March 30 2018

Estimated Enrollment :

37 Patients enrolled

Trial Details

Trial ID

NCT00968968

Start Date

January 20 2010

End Date

March 30 2018

Last Update

June 10 2019

Active Locations (116)

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Page 1 of 29 (116 locations)

1

Novartis Investigative Site

Chandler, Arizona, United States, 85224

2

Novartis Investigative Site

Flagstaff, Arizona, United States, 86001

3

Novartis Investigative Site

Gilbert, Arizona, United States, 85297

4

Novartis Investigative Site

Mesa, Arizona, United States, 85202