A Phase III trial to compare the safety and efficacy of lapatinib plus trastuzumab plus an aromatase inhibitor (AI) versus trastuzumab plus an AI versus lapatinib plus an AI as first-line therapy in postmenopausal subjects with hormone receptorpositive, HER2-positive metastatic breast cancer (MBC) who have received trastuzumab and endocrine therapy in the neoadjuvant and/or adjuvant setting
- Conditions
- HER2-positive metastatic breast cancer who have received trastuzumab and endocrine therapy in the neoadjuvant and/or adjuvant settingMedDRA version: 19.0Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2010-019577-16-HU
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 345
Refer to the authorized prescribing information for lapatinib [TYKERB
Package Insert, 2010], trastuzumab [HERCEPTIN Package Insert, 2009],
letrozole [FEMARA Package Insert, 2010], anastrozole [ARIMIDEX
Package Insert, 2009], and exemestane [AROMASIN Package Insert,
2008] for specific information regarding warnings, precautions,
contraindications, adverse events, and other pertinent information on the study treatment(s) that may impact subject eligibility.
Deviations from inclusion criteria are not allowed because they can
potentially jeopardize the scientific integrity of the study, regulatory
acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Signed written informed consent
2. Post-menopausal female subjects =18 years of age. Post-menopausal as defined
by any of the following:
• Age > 60 years
• Age = 45 years with amenorrhea > 12 months with an intact uterus
• Having undergone a bilateral oophorectomy or radiation castration with
amenorrhea for at least 6 months
• FSH and estradiol levels in postmenopausal range (utilizing ranges from the
local laboratory facility). In subjects who have previously been treated with
an GnRH/LHRH analogue, the last injection must have been administered >
4 months prior to randomization and menses must not have restarted
3. Histologically confirmed Stage IV invasive breast cancer
• Subjects may have either measurable or non-measurable disease per Response
Evaluation Criteria in Solid Tumors (RECIST 1.1) [Eisenhauer, 2009]
4. Tumors that are ER+ and/or PgR+ by local laboratory
5. Documentation of HER2 overexpression or gene amplification, in the invasive
component of either the primary tumor or metastatic disease site as defined as:
• 3+ by Immunohistochemistry (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 test ratio (HER2 gene copies to chromosome 17
signals) of =2.0]
6. Subject must have received at least one prior regimen containing
trastuzumab in combination with chemotherapy for breast cancer:.
- Subject has ONLY received prior trastuzumab in combination with
chemotherapy as neoadjuvant and/or adjuvant treatment.
OR
- Subject has received ONE prior trastuzumab-containing regimen for
metastatic disease (and has progressed), and may or may not have
received prior trastuzumab in combination with chemotherapy as
neoadjuvant and/or adjuvant treatment
7. Subject must have received prior endocrine therapy (such as aromatase inhibitors or selective estrogen receptor modulators).
8. Subjects who have a life expectancy of > 6 months as assessed by the treating
investigator
9. Subjects must have baseline Left Ventricular Ejection Fraction (LVEF)
>=50% measured by echocardiography (ECHO) or multi-gated
acquisition scan (MUGA)
10. Subject must have an ECOG performance status of 0-1 (Section 12.2, Appendix 2)
11. All prior treatment related toxicities must be CTCAE (Version 4.0) = Grade 1 [NCI, 2009] at the time of randomization
12. Completion of screening assessments
13. Adequate baseline organ function defined by: (Refer to Table 1)
14. Subjects must meet all of the following criteria:
- QTc <450msec or
- QTc <480msec for subjects with bundle branch block
The QTc is
Subjects meeting any of the following criteria must not be enrolled in the study:
1. History of another malignancy.
Exception: Subjects who have been disease-free for 5 years, or subjects with a
history of completely resected non-melanoma skin cancer or successfully treated
in situ carcinoma are eligible.
2. Subjects with extensive symptomatic visceral disease including hepatic
involvement and pulmonary lymphangitic spread of tumor, or the disease is
considered by the investigator to be rapidly progressing or life threatening
(subjects who are intended for chemotherapy)
3. Serious cardiac illness or medical condition including but not confined to:
• Uncontrolled arrhythmias
• Uncontrolled or symptomatic angina
• History of congestive heart failure (CHF)
• Documented myocardial infarction <6 months from study entry
4. Known history of, or clinical evidence of, central nervous system (CNS)
metastases or leptomeningeal carcinomatosis
5. Have acute or currently 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)
6. Have a 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)
7. Have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
8. Have a 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, contraindicates their participation
9. Any prohibited medication as described in Section 6.2.
10. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method