A Multicenter, Open-Label, Phase II Study of Lapatinib in Combination With Vinorelbine in Subjects With ErbB2 Amplified Recurrent and Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- lapatinib and Vinorelbine
- Conditions
- Cancer
- Sponsor
- GlaxoSmithKline
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Number of Participants (Par.) With Clinical Benefit (CB) at Week 12 and Week 24
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This is a Multicenter, Open-Label, Phase II Study of lapatinib in Combination with Vinorelbine in women with documented evidence of HER2/neu positive breast cancer which is metastatic or recurrent and with or without prior chemotherapy or anti-HER2/neu targeted therapy in the metastatic and relaps setting.
Detailed Description
This is a Multicenter, Open-Label, Phase II Study of lapatinib in Combination with Vinorelbine in women with documented evidence of HER2/neu positive breast cancer which is metastatic or recurrent and with or without prior chemotherapy or anti-HER2/neu targeted therapy in the metastatic and relaps setting. Patients will receive 1250mg lapatinib once a day and vinorelbine 25mg/sqm IV Day 1and Day 8, every 3 week for 24 weeks. The study treatment will continue until patients experience disease progression or unacceptable toxicity. The primary objective of the study is the objective response rate (ORR, defined as CR + PR) and toxicity. Secondary objectives include DFS, duration of response.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed adenocarcinoma of the breast.
- •Patients must be \> 18 years of age
- •Metastatic breast cancer (stage IV) at primary diagnosis or at relapse after curative intent therapy.
- •Laboratory confirmed HER2/neu overexpressing and/or amplified disease in the invasive component of the primary or metastatic lesion
- •Patients must have evidence of metastatic disease, but measurable disease is not mandatory.
- •The patients may have received or not prior treatment with chemotherapeutic agents including taxanes, trastuzumab or anthracycline in the adjuvant or metastatic setting is permitted.
- •Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are permitted provided that at least 4 weeks have elapsed since the last fraction of radiation therapy and all treatment related adverse events are \< grade 1 at the time of enrollment.
- •Prior radiation to a solitary metastatic lesion is permitted provided that progression post radiation has been documented.
- •Patients must have life expectancy \> 3 months.
- •ECOG performance status 0, 1 or 2 (see Appendix II).
Exclusion Criteria
- •Patients with a history of other malignancies, except: adequately treated DCIS, adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours (non-breast) curatively treated with no evidence of disease for \> 5 years.
- •Patients receiving ongoing anticancer treatment or other investigational anti-cancer agents for breast cancer or patients who have used an investigational drug within 30 days or 5 half-lives (if known), whichever is longer, preceding the date of enrollment.
- •Patients with symptomatic CNS metastases (including leptomeningeal involvement).
- •Patients with only bone metastasis.
- •Patients with serious cardiac illness or condition including, but not limited to:
- •history of documented congestive heart failure (CHF) or systolic dysfunction (LVEF\<50%) high risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled) unstable angina pectoris requiring anti-anginal medication clinically significant valvular heart disease evidence of transmural infarction on ECG inadequately controlled hypertension (systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 100 mmHg).
- •New York Heart Association (NYHA) Class III or IV functional status (see Appendix X)
- •Patients who have received vinorelbine as a prior therapy in the metastatic and recurrent setting.
- •Patients with serious illness or medical condition which would not permit the patient to be managed according to the protocol including, but not limited to:
- •History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
Arms & Interventions
lapatinib 1250mg
Patients will receive 1250mg lapatinib once a day for 24 weeks.
Intervention: lapatinib and Vinorelbine
Vinorelbine 25mg/sqm
Patients will receive vinorelbine 25mg/sqm IV Day 1 and Day 8, every 3 week for 24 weeks.
Intervention: lapatinib and Vinorelbine
Outcomes
Primary Outcomes
Number of Participants (Par.) With Clinical Benefit (CB) at Week 12 and Week 24
Time Frame: Week 12 and Week 24
Par. with CB are defined as those with complete response (CR), partial response (PR), or stable disease (SD) for \>=12 or 24 weeks. Per Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1, CR is defined as the disappearance of all target lesions, PR is defined as a \>=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD, and SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as a reference the smallest sum LD since the treatment started.
Secondary Outcomes
- Progression-free Survival(From the start of treatment until disease progression, death, or discontinuation from the study (average of 102.7 months))
- Duration of Response(From the start of treatment until a complete response or partial response was reached (up to Week 90; average of 21.3 weeks))