Randomized Phase II Study of Lapatinib Plus Vinorelbine Versus Vinorelbine in Patients With HER2 Positive Metastatic Breast Cancer Progressed After Lapatinib and Trastuzumab Treatment
Overview
- Phase
- Phase 2
- Intervention
- Lapatinib
- Conditions
- Metastatic Breast Cancer
- Sponsor
- National Cancer Center, Korea
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- Progression free survival rate at 18 weeks
- Last Updated
- 12 years ago
Overview
Brief Summary
The investigators address the clinical efficacy of continuing lapatinib treatment combined with vinorelbine after the progression of both trastuzumab and lapatinib treatment compared with vinorelbine alone in HER2 positive metastatic breast cancer patients.
Detailed Description
This study is a multicenter, randomized, open label, phase II study. Patients will be randomized to either lapatinib plus vinorelbine (LV) arm or vinorelbine alone (V) arm, if they are satisfied by inclusion and exclusion criteria. The stratification factors are followings: 1) visceral metastasis vs. others, 2) previous response to lapatinib treatment, complete response(CR)+partial response(PR) vs. stable disease(SD)≥ 12wks. Patients in LV arm will receive daily lapatinib 1,000mg with vinorelbine 20mg/m2 day1 and day 8. Patients in V arm will receive vinorelbine 30mg/m2 day 1 and day 8. Treatment repeats every 21 days unless there is any evidence of disease progression or unacceptable toxicity or noncompliance by patient with protocol requirements. Response will be documented by physical examination, chest or abdomen CT prior to treatment as a baseline, and every 2 cycles (window period ± 1 week) after a start of treatment and at 18 weeks.
Investigators
Jungsil Ro
Chief, Center for Clinical Trials
National Cancer Center, Korea
Eligibility Criteria
Inclusion Criteria
- •Confirmed stage IV or recurrent breast cancer
- •Documented HER2 status and positive for HER2 in tumor cells by immunohistochemistry (3+) or FISH (The results of SISH or CISH are also allowed)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Age ≥ 20 years
- •Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1
- •Patients who were treated with anthracycline based regimens in the adjuvant/neoadjuvant or metastatic setting.
- •Patients who experienced disease progression after the treatment with lapatinib containing regimens whose response were more than stable disease (including CR, PR, SD≥ 12 weeks) during treatment. There is no limitation on the time interval between the stop of lapatinib treatment and the study enrollment.
- •Patients must have received 2 or 3 lines of prior anti-HER2 therapy in metastatic setting as follows regardless of the order
- •In case with trastuzumab: monotherapy or combined with taxane or combined with AI
- •In case with lapatinib: monotherapy or combined with capecitabine or combined with AI
Exclusion Criteria
- •Pregnant or lactating women or women of childbearing potential, including women whose last menstrual period was ,12 months ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during the study treatment period.
- •Patients who received vinorelbine treatment in metastatic setting.
- •Patients who received more than 3 lines of prior anti-HER2 therapy in metastatic setting
- •Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
- •Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative colitis)
- •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)
- •Concurrent disease or serious medical disorder,
- •Serious cardiac illness :
- •History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF \<50%) High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade atrioventricular (AV)-block,supraventricular arrhythmias, prolonged corrected QT (QTc) which are not adequately rate-controlled) Angina pectoris requiring antianginal medication Clinically significant valvular heart disease Evidence of transmural infarction on ECG Poorly controlled hypertension (e.g. systolic \>180mm Hg or diastolic \>100mm Hg)
- •known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients.
Arms & Interventions
Lapatinib+Vinorelbine
lapatinib 1000mg, once daily vinorelbine 20mg/m2, D1 and D8, every 3 weeks
Intervention: Lapatinib
Lapatinib+Vinorelbine
lapatinib 1000mg, once daily vinorelbine 20mg/m2, D1 and D8, every 3 weeks
Intervention: Vinorelbine
Outcomes
Primary Outcomes
Progression free survival rate at 18 weeks
Time Frame: The time point of 18 weeks from the initiation of study treatment.
The PFS rate at 18 weeks will be calculated as the ratio of patients on the study to Intent to treat (ITT) population at the time point of 18 weeks from the initiation of study treatment. The ITT population will consist of all patients who are randomized.
Secondary Outcomes
- Progression free survival (PFS)(From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months)
- Overall survival (OS)(From date of randomization until the date of death from any cause, assessed up to 36 months)
- toxicity(From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months)
- response rate(From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months)