Breast Cancer (with ErbB2 Overexpressing Metastatic Breast Cancer) MedDRA version: 15.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to registration. 2. Considered by the investigator to have a life expectancy of =12 weeks. 3. Subjects must be female and have histologically-confirmed invasive breast cancer with Stage IV disease at primary diagnosis or at relapse after curative-intent surgery. Where the disease is restricted to a solitary lesion, the neoplastic nature of the lesion should be confirmed by cytology or histology. 4. Documented overexpression of ErbB2 by 3+ immunohistochemistry or a positive score by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridisation (CISH) using a local laboratory result on a specimen from the primary tumour or visceral metastatic site. Verification by a central laboratory is not required. 5. Subjects should have progressive disease following prior therapy which may include anthracyclines, taxanes, and trastuzumab. Subjects who have not received prior treatment for MBC must fulfill one or more of the following conditions: 1) Relapse following receipt of trastuzumab-based therapy in the adjuvant setting, 2) Contraindication to receiving trastuzumab or documented medical reason for trastuzumab not being appropriate, as determined by the study investigator, or 3) Unsuitable for taxane-based chemotherapy as determined by the study investigator. 6. All prior chemotherapy, immunotherapy, biologic therapy, or surgery (except for minor surgical procedures) must be discontinued or completed at least 4 weeks prior to first dose of randomized study medication. Hormonal therapy must be discontinued at least 1 week prior to first dose. 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. 7. Prior diagnosis of non-breast cancer is allowed as long as the subject is free of disease and has not received treatment for prior malignancies for at least 5 years. Subjects with completely resected basal or squamous cell skin cancer or successfully treated cervical carcinoma in situ will be allowed if it has been 1 year or longer since definitive and curative surgery. 8. Females aged =18 years with any menopausal status: • Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal). • Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility): This category includes women with oligomenorrhea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following: • Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or • Consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female subject; any intrauterine device or contraceptive method with a documented failure rate of less than 1% per year 9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1. 10. Subjects must have adequate organ and marrow function as defined view protocol for further information. 11. Su
Exclusion criteria
Exclusion criteria: 1. Subjects taking medications listed in Section 5.9.2 of the protocol are not eligible for the study. This includes human immunodeficiency virus-positive subjects receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with lapatinib. 2. Therapy with lapatinib, vinorelbine, or capecitabine prior to randomization into this study. 3. Prior therapy with more than one chemotherapeutic regimen for metastatic breast cancer. 4. Concurrent anticancer or concomitant radiotherapy treatment. 5. History of uncontrolled or symptomatic angina; history of arrhythmias requiring medications; clinically significant myocardial infarction <6 months from study entry; uncontrolled or symptomatic congestive heart failure; ejection fraction below the institutional normal limit; or any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. 6. Have 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). 7. Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of investigational treatment, or, concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents. 8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the agents used in this study or their excipients that in the opinion of the investigator or GSK Medical Monitor contraindicates their participation. 9. Known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD). 10. Known history of uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 11. Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject’s safety. 12. Pregnant or lactating females at any time during the study (due to the potential teratogenic or abortifacient effects of lapatinib and breastfeeding). 13. Subjects with diseases affecting gastrointestinal function resulting in an inability to take oral medication, including; malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, small bowel, or colon. Subjects with inflammatory bowel disease or ulcerative colitis are also excluded. 14. Peripheral neuropathy of Grade 2 or greater. 15. Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment. 16. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate progression-free survival (PFS) in women with ErbB2-overexpressing MBC treated with lapatinib in combination with vinorelbine or lapatinib in combination with capecitabine, who have received no more than 1 prior chemotherapeutic regimen in the metastatic setting.;Secondary Objective: To evaluate the two treatment arms for the following: • Overall response rate (ORR) [complete response (CR) and partial response (PR)] • Overall survival (OS) • Duration of response • Time to response • Clinical Benefit Rate (CBR) • Qualitative and quantitative toxicities • To characterize the PK of vinorelbine alone and in combination with lapatinib in a subgroup of subjects (at selected sites) receiving this combination Exploratory Objectives • For patients who experience disease progression on their randomized treatment arm and elect to continue in the post-progression cross-over phase, time to second progression following cross-over will be evaluated as an exploratory objective. • This study will collect pharmacogenetics samples for exploratory research, as described in Appendix 3 of the protocol.;Primary end point(s): The primary efficacy analysis will be based on PFS. PFS is the primary endpoint and is defined as the interval between the date of randomization and the date of objective disease progression or death from any cause. Disease progression will be based on the assessments from the investigator review of objective evidence of progression (e.g., radiological scans and medical photographs). | — |
Countries
Bulgaria, France, Germany, Greece, Italy, Spain
Outcome results
None listed