A study to compare the safety and efficacy of an aromatase inhibitor in combination with lapatinib, trastuzumab or both for the treatment of hormone receptor positive, HER2+ metastatic breast cancer

Phase 3

Suspended

• Conditions: Hormone receptorpositive, HER2-positive metastatic breast cancer (MBC)

• Registration Number: CTRI/2012/11/003101
• Lead Sponsor: GlaxoSmithKline Pharmaceuticals Ltd

Brief Summary

Breast cancer is the most common form of cancer and the second leading cause of cancer-related deaths (after lung cancer) in women. Despite significant improvements in early diagnosis, all patients withMBC, and up to 40% of patients receiving adjuvant endocrine therapy, progress and die from the disease, demonstrating a medical need for improved therapies.

The current protocol, EGF114299 is designed to demonstrate a benefit in overall survival (OS) provided by lapatinib in HR+/HER2-positive patients who have been previously exposed to neoadjuvant and/or adjuvant trastuzumab. It will also provide further data to understand the role of dual HER2 suppression in this patient population. This study will enroll post-menopausal women who have recurrent disease after neoadjuvant and/or adjuvant therapy including trastuzumab and endocrine therapy which is being undertaken as a postmarketing requirement with regulatory authorities.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-02-16
• Last Update Posted: 2016-03-04

Recruitment & Eligibility

• Status: Suspended
• Sex: Female
• Target Recruitment: 525

Inclusion Criteria

• 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 prior neoadjuvant and/or adjuvant trastuzumab 7.
• Subject must have received prior neoadjuvant and/or adjuvant endocrine therapy 8.
• Subjects who have a life expectancy of > 6 months as assessed by the treating investigator 9.
• Have baseline of Left Ventricular Ejection Fraction (LVEF) ≥50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA) 10.
• ECOG performance status of 0-1 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.

Exclusion Criteria

• Deviations from exclusion 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 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.
• 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.
• Subjects who received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or anti-HER2 therapy for advanced or metastatic disease 4.
• 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 5.
• Known history of, or clinical evidence of, central nervous system (CNS)metastases or leptomeningeal carcinomatosis 6.
• Current active hepatic or biliary disease (with exception of subjects with Gilberts syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 7.
• 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) 8.
• Have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels 9.
• 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 10.
• Any prohibited medication 11.
• 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
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Demonstrate superiority of lapatinib/trastuzumab/AI combination (Treatment Group A) vs. trastuzumab/AI combination (Treatment Group B) for overall survival.	Death.

Secondary Outcome Measures

Name	Time	Method
To compare OS in Treatment Group B (trastuzumab/AI) vs. Treatment Group C (lapatinib/AI) and Treatment Group A (trastuzumab/lapatinib/AI) vs. Treatment Group C (lapatinib/AI)	Death.
To compare progression free survival (PFS) in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C ( lapatinib/AI) vs. Treatment Group B (trastuzumab/AI)	Disease Progression
To compare overall response rate (complete or partial response), time to response, and duration of response in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI)	Disease Progression
To compare clinical benefit (complete response, partial response, or stable disease for at least 6 months) in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI)	Disease Progression
To evaluate the safety and tolerability of all three	treatment groups (lapatinib/trastuzumab/AI, trastuzumab/ AI, or lapatinib/AI)
To compare Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI) with respect to change in quality of life (QoL) status relative to baseline.	Day 1 pre-dose, every 12 weeks, and at discontinuation of study treatment

Trial Locations

Locations (7)

Apollo Hospital Educational & Research Foundation; 🇮🇳 South, DELHI, India

Bharat Cancer Hospital & Research Institute; 🇮🇳 Surat, GUJARAT, India

Central India Cancer Research Institute; 🇮🇳 Nagpur, MAHARASHTRA, India

Rajiv Gandhi Cancer Institute and Research Centre; 🇮🇳 North, DELHI, India

Ruby Hall Clinic; 🇮🇳 Pune, MAHARASHTRA, India

Sri Ramachandra Medical College; 🇮🇳 Chennai, TAMIL NADU, India

Vikram Hospital Bengaluru Private Limited; 🇮🇳 Bangalore, KARNATAKA, India

Apollo Hospital Educational & Research Foundation

🇮🇳South, DELHI, India

Dr Rakesh Chopra

Principal investigator

91-9810034598

rakc1@rediffmail.com