| CTRI Number |
CTRI/2012/11/003101 [Registered on: 09/11/2012] Trial Registered Prospectively |
| Last Modified On: |
03/04/2016 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
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Public Title of Study
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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 |
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Scientific Title of Study
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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 receptor positive, HER2-positive metastatic breast cancer (MBC) who have received trastuzumab and endocrine therapy in the neo/adjuvant setting. |
| Trial Acronym |
ALTERNATIVE |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| EGF114299 |
Other |
| NCT01160211 |
ClinicalTrials.gov |
| UM2010/00099/02 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Dr Vrishali Desai |
| Designation |
Medical Director |
| Affiliation |
GlaxoSmithKline Pharmaceuticals Limited |
| Address |
GlaxoSmithKline Pharmaceuticals Limited
400 030
India
252, Dr. Annie Besant Road, Worli
Mumbai
MAHARASHTRA
400030
India |
| Phone |
912224959581 |
| Fax |
912224946339 |
| Email |
vrishali.r.desai@gsk.com |
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Details of Contact Person
Public Query
Modification(s)
|
| Name |
Kedar Nayak |
| Designation |
Area Manager_In-Country Clinical Operations |
| Affiliation |
GlaxoSmithKline Pharmaceuticals Limited |
| Address |
GlaxoSmithKline Pharmaceuticals Ltd.
252, Dr. A.B. Road,
Worli
Mumbai
MAHARASHTRA
411 030
India |
| Phone |
91-22-24959508 |
| Fax |
91-22-24947415 |
| Email |
kedar.n.nayak@gsk.com |
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Source of Monetary or Material Support
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| GlaxoSmithKline Pharmaceuticals Ltd. |
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Primary Sponsor
|
| Name |
GlaxoSmithKline Pharmaceuticals Ltd |
| Address |
GlaxoSmithKline Pharmaceuticals Ltd. 252, Dr. A.B. Road, Mumbai 400030. India. |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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Countries of Recruitment
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India
Argentina
Australia
Belgium
Brazil
Bulgaria
Canada
Colombia
Croatia
Democratic People's Republic of Korea
Denmark
Finland
France
Germany
Greece
Hong Kong
Ireland
Israel
Italy
Japan
Lithuania
Norway
Peru
Philippines
Poland
Portugal
Romania
Russian Federation
Serbia
Singapore
South Africa
Spain
Taiwan
Ukraine
United Kingdom
United States of America |
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Sites of Study
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| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Rakesh Chopra |
Apollo Hospital Educational & Research Foundation |
Department of Medical Oncology, Basement Complex,
Indraprastha Apollo Hospitals,
Delhi Mathura Road,
Sarita Vihar,
New Delhi-110 076
South
DELHI |
91-9810034598
91-11-41677024
rakc1@rediffmail.com |
| Dr Tanveer Maksud |
Bharat Cancer Hospital & Research Institute |
Department of Medical Oncology,Surat-Bardoli Road, Saroli - 394601
Surat
GUJARAT |
91-9909918887
91-261-2641005
tanveermaksud@yahoo.com |
| Dr Ajay Mehta |
Central India Cancer Research Institute |
Department of Medical Oncology, 11 Shankar Nagar,
West High Court Road,
Nagpur 440010
Nagpur
MAHARASHTRA |
91-9823190192
91-712-2523404
ajayonco@hotmail.com |
| Dr Dinesh C Doval |
Rajiv Gandhi Cancer Institute and Research Centre |
Department of Medical Oncology, Sector V, Rohini,
New Delhi - 110 085
North
DELHI |
91-9810836274
91-11-27931342
ddoval07@gmail.com |
| Dr Minish Jain |
Ruby Hall Clinic |
Department of Medical Oncology, Cancer Centre,
40, Sassoon Road,
Pune- 411 001
Pune
MAHARASHTRA |
91-20-56012244
91-20-66455604
minishjain009@rubyhallclinic.com |
| Dr Anita Ramesh |
Sri Ramachandra Medical College |
Department of Medical Oncology,
No 1, Ramachandra Nagar,
Porur, Chennai – 600116
Chennai
TAMIL NADU |
91-9840758567
91-44-45928678
anitachandra100@hotmail.com |
| Dr Niti Narang |
Vikram Hospital Bengaluru Private Limited |
Department of Medical Oncology,
#71/1 Millers Road,
Bengaluru – 560052
Bangalore
KARNATAKA |
91-9611803014
91-80-45004699
nitiraizada@yahoo.co.uk |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 7 |
| Name of Committee |
Approval Status |
| Bangalore Ethics, Bengaluru |
Approved |
| Central India Cancer Research Institute Ethics Committee, Nagpur |
Approved |
| Ethical Trial of Health In Community (ETHIC) Committtee, Surat |
Approved |
| Ethics Committee on Clinical Trials, Indraprastha Apollo Hospitals, New Delhi |
Approved |
| Institutional Ethics Committee, Sri Ramachandra Medical College, Chennai |
Approved |
| Institutional Review Board, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi |
Approved |
| Poona Medical Research Foundation, Pune |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Hormone receptor
positive, HER2-positive metastatic breast cancer (MBC), |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Comparator Agent |
Aromatase Inhibitor |
Oral Administration. Choice of letrozole (2.5 mg) or anastrozole (1 mg) or exemestane (25 mg) given once daily in all 3 treatment arms (A, B and C). Study treatment will be administered until disease progression or discontinuation of study treatment due to unacceptable toxicity or other reasons (i.e., consent withdrawal, non-compliance) |
| Intervention |
Lapatinib |
Oral administration. Treatment Group A : 1000 mg and Treatment Group C : 1500 mg. Study treatment will be administered until disease progression or discontinuation of study treatment due to unacceptable toxicity or other reasons (i.e., consent withdrawal, non-compliance) |
| Comparator Agent |
Trastuzumab |
Trastuzumab:
Intravenous Administration of 8 mg/kg (loading dose) followed by 6 mg/kg every 3 weeks. Applicable only to Arms A and B. Study treatment will be administered until disease progression or discontinuation of study treatment due to unacceptable toxicity or other reasons (i.e., consent withdrawal, non-compliance) |
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Inclusion Criteria
Modification(s)
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| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Female |
| Details |
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 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 |
|
| ExclusionCriteria |
| Details |
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.
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. 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. |
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Method of Generating Random Sequence
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Computer generated randomization |
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Method of Concealment
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On-site computer system |
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Blinding/Masking
|
Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
| Demonstrate superiority of lapatinib/trastuzumab/AI combination (Treatment Group A) vs. trastuzumab/AI combination (Treatment Group B) for overall survival. |
Death. |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| 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) |
Death or Disease Progression |
| 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 |
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Target Sample Size
Modification(s)
|
Total Sample Size="525"
Sample Size from India="75"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
16/02/2013 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
05/05/2011 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
|
Years="15"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Suspended |
Publication Details
Modification(s)
|
Publication currently not available. |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
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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. |