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.
- Conditions
- Metastatic breast cancer overexpressing ErbB2MedDRA version: 9.1Level: LLTClassification code 10006202Term: Breast cancer stage IV
- Registration Number
- EUCTR2008-000673-38-GR
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 650
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. 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
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,CISH or SISH;
• ErbB2 gene amplification by FISH, CISH or SISH 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]
• 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.
NOTE: Pleural effusion or ascites (without cytologic verification) as the only
evidence of metastatic disease do not meet the eligibility criteria.
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 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 not lower than the institutional lower limit of normal
measured by echocardiography or MUGA scan;
NOTE: The same modality used at baseline must be used for repeat assessment
throughout study.
14. Concurrent treatment with bisphosphonates is permitted; however treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in subjects without bone disease is not permitted, except for the treatment of osteoporosis;
15. Able to swallow and retain oral medications;
16. A female who is of:
• non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
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 ha
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). or evidence of benign or malignant brain tumors and/or evidence of
spinal cord metastases at Baseline. Any evidence of brain metastases on Baseline
MRI scan (performed within 4 weeks prior to randomization) as determined by
Independent Reviewer;
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(including
but not limited to trastuzumab-DM1 and neratinib);
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 Section 4.11.2, Prohibited
Medications and Non-Drug Therapies;
11. Concomitant use of CYP3A4 inhibitors or inducers (also refer to Table 7 in protocol);
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. Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the 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 except alopecia;
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 (if in accord with the policies of the
local Ethics Committee);
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,
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