A Randomized, Multicentre, Open-Label, Phase III Study of Lapatinib plus Capecitabine versus Trastuzumab plus Capecitabine in Patients with Anthracycline- or Taxane-Exposed ErbB2-Positive Metastatic Breast Cancer.

Phase 1

• Conditions: Metastatic breast cancer overexpressing ErbB2; MedDRA version: 9.1Level: LLTClassification code 10006202Term: Breast cancer stage IV

• Registration Number: EUCTR2008-000673-38-FR
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11-25
• Last Update Posted: 28 May 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 650

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Able to give signed written informed consent
2. Females age = 18 years old
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;
4. Life expectancy of at least 12 weeks
5. Subjects must have histologically or cytologically confirmed invasive breast cancer,
with Stage IV disease
• If the metastatic disease is restricted to a solitary lesion, its neoplastic nature
should be confirmed by cytology or histology.
6. ErbB2 overexpression in the invasive component of the primary or metastatic lesion as locally defined by:
• 3+ staining by immunohistochemistry (IHC);
• or 2+ staining by IHC in conjunction with ErbB2 gene amplification by FISH;
• ErbB2 gene amplification by FISH;
• subjects with a negative or equivocal overall result are not eligible for
participation in the trial.
7. Subjects must have evidence of metastatic disease, but measurable disease is not
mandatory.
8. Prior treatment with taxanes or anthracyclines is required. All treatment related
adverse events must be = Grade 1 at the time of randomization
9. Prior treatment with other chemotherapeutic agents is permitted provided that all
treatment related adverse events are = Grade 1 at the time of randomization
10. Prior treatment with trastuzumab is permitted provided that at least 6 weeks has
elapsed since the last dose of therapy and all treatment related adverse events are
= Grade 1 at the time of randomization
11. Prior treatment with endocrine therapy is permitted provided that therapy has been discontinued and all treatment related adverse events are = Grade 1 at the time of randomization
12. Prior treatment with radiation therapy is permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy and all treatment related adverse events are = Grade 1 at the time of randomization
13. Baseline LVEF = 50% and above the institutional lower limit of normal measured by echocardiography or MUGA scan
14. Concurrent treatment with bisphosphonates is permitted; however treatment must be initiated prior to the first dose of study therapy
15. Able to swallow and retain oral medications;
16. A female who is of:
• non-childbearing potential, including any female who has had hysterectomy, a bilateral oopheroctemy, bilateral tubular ligation or is post-menopausal (total cessation of menses for = 1 year
• childbearing potential who must have a negative serum pregnancy test within 2
weeks prior to the first dose of study treatment, preferably as close to the first
dose as possible, and agrees to use adequate contraception (for example,
intrauterine device [IUD], birth control pills unless clinically contraindicated, or
barrier device) beginning 2 weeks before the first dose of investigational product
and for 28 days after the final dose of investigational product.
17. Subjects must complete all screening assessments as outlined in the protocol
18. Subjects must have normal organ and marrow function.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1. History and/or current evidence of CNS metastases (including leptomeningeal
involvement). Absence of CNS metastases must be confirmed by a brain MRI scan
performed within 2 weeks prior to randomization
2. Concurrent treatment with an investigational agent or participation in another
treatment clinical trial
3. Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab
4. Prior treatment with capecitabine
5. Known dihydropyrimidine dehydrogenase (DPD) deficiency
6. ECOG Performance Status >2
7. Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy
(including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of
cancer
8. History of allergic reactions attributed to compounds of similar chemical
composition to lapatinib (quinazolines)
9. History of allergic reactions attributed to compounds chemically related to
capecitabine, fluorouracil or any excipients
10. Concurrent treatment with medications listed in the protocol (Section 4.11.2 Prohibited Medications and Non-Drug Therapies)
11. Concomitant use of CYP3A4 inhibitors or inducers
12. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
13. History of immediate or delayed hypersensitivity reaction to gadolinium contrast
agents, or other contraindication to gadolinium contrast
14. Compromised renal function that would exclude subjects from receiving gadolinium based contrast agents as guided by local institutional policy
15. Other known contraindication to MRI, such as a cardiac pacemaker, implanted
cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or
shrapnel
16. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety or compliance to study procedures
17. Current active hepatic or biliary disease (with exception of patients with Gilbert's
syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease
per investigator assessment)
18. Any on-going toxicity from prior anti-cancer therapy that is > Grade 1 and/or is
progressing in severity
19. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent, unless a legally acceptable
representative could provide informed consent
20. Active cardiac disease, defined as one or more of the following:
• History of uncontrolled or symptomatic angina
• History of arrhythmias requiring medications, or clinically significant
• Myocardial infarction < 6 months from study entry
• Uncontrolled or symptomatic congestive heart failure
• Cardiac angioplasty or stenting
• Ejection fraction below the institutional normal limit
• History of documented congestive heart failure (CHF) or systolic dysfunction;
• Clinically significant valvular heart disease
• Any other cardiac condition, which in the opinion of the treating physician
would make this protocol unreasonably hazardous for the patient.
21. Uncontrolled infection
22. History of other malignancy, except for curatively treated basal cell carcinoma or
squamous cell carcinoma of the skin, or carcinoma in situ of the cervix; subjects with
other malignancies who have been disease-free for at least 5 years are eligible;
23. Used an investigat

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effect of lapatinib plus capecitabine on incidence of CNS as site of first relapse as compared with trastuzumab plus capecitabine;Secondary Objective: To evaluate and compare the two treatment arms for the following:<br>• Progression free survival<br>• Time to first CNS progression<br>• Overall survival<br>• Overall response rate (CR or PR)<br>• Clinical benefit response rate (confirmed CR or PR at any time or SD for = 24<br>weeks )<br>• Duration of response<br>• Incidence of CNS progression at any time (brain scans will not be required following<br>non-CNS progression; therefore incidence of CNS progression at any time will<br>include progression documented by brain scan on study as well as CNS progression<br>as indicated by the investigator on follow-up eCRF page).<br>• The qualitative and quantitative toxicities.;Primary end point(s): Incidence of CNS as a site of first relapse of metastatic disease.