A study to compare the safety and efficacy of an aromatase inhibitor in combination with lapatinib or trastuzumab, or both for the treatment of hormone receptor positive, HER2+ metastatic breast cancer
- Conditions
- HER2-positive metastatic breast cancer who have received prior trastuzumab and endocrine therapiesMedDRA version: 16.1Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-019577-16-LT
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 525
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.
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Signed written informed consent. In Korea and Japan, subjects who are between =18 and <20 years of age must also have a legal representative sign the written informed consent.
2. Post-menopausal female subjects =18 years of age. Post-menopausal as defined by any of the following:
•Subjects at least 60 years of age.
•Subjects under 60 years of age and amenorrhic for at least 12 consecutive months AND follicle-stimulating hormone (FSH) and estradiol levels in postmenopausal range (utilizing ranges from the local laboratory facility).
•Prior bilateral oophorectomy.
•Prior radiation castration with amenorrhea for at least 6 months
3. Subjects must have a history of histologically confirmed breast cancer, with a clinically confirmed diagnosis of metastatic disease [confirmed by histology, cytology or other clinical means (e.g. CT, MRI)]. 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 Protocol page 27)
14. Subjects must meet all of the following criteria:
•QTc <450msec or
•QTc <480msec for subjects with bundle branch block
The QTc is the QT interval corrected for heart rate according to either Bazett’s formula (QTcB) or to Fridericia’s formula (QTcF),
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