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 - ND

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

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-31
• Last Update Posted: 5 August 2013

Recruitment & Eligibility

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

Inclusion Criteria

1.Signed written informed consent; 2.Females age ³ 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. To be considered evaluable for the overall response rate ( partial response), subjects must have at least one measurable lesion; 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 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; 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 proto

Exclusion Criteria

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 Section 4.11.2, Prohibited Medications and Non-Drug Therapies; 11. Concomitant use of CYP3A4 inhibitors or inducers (also refer to Table 7); 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 (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, 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 l

Study & Design

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