A Phase II, Randomized, Open-label Study of Lapatinib Plus Chemotherapy Versus Trastuzumab Plus Chemotherapy as First-line Treatment for Women With HER2-positive and p95HER2-positive Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Lapatinib
- Conditions
- Neoplasms, Breast
- Sponsor
- GlaxoSmithKline
- Primary Endpoint
- Progression-free survival
- Status
- Withdrawn
- Last Updated
- 13 years ago
Overview
Brief Summary
This is a Phase II, randomized, open-label, multi-center study evaluating the efficacy and safety of lapatinib in combination with chemotherapy versus trastuzumab in combination with chemotherapy in women with HER2-positive and p95HER2-positive metastatic breast cancer (MBC). Eligible subjects will have newly diagnosed metastatic breast cancer (Stage IV) either as a primary diagnosis or as a recurrence following treatment of curative intent; not have received systemic or local treatment for MBC and have breast cancer that is positive for HER2 and p95HER2. The primary objective is to compare progression-free survival (PFS) of lapatinib plus chemotherapy versus trastuzumab plus chemotherapy as first-line treatment in subjects with MBC exhibiting concurrent HER2 overexpression (and/or gene amplification) and expression of carboxy-terminal fragments of HER2 (p95HER2). The secondary objectives are to evaluate overall survival, overall response rate, clinical benefit response rate and the safety as well as tolerability of lapatinib plus chemotherapy and trastuzumab plus chemotherapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female ≥ 18 years of age
- •Histologically or cytologically confirmed invasive breast cancer with distant metastasis(ses) (designated as Stage IV or metastatic breast cancer)
- •Diagnosis with Stage IV or metastatic disease at either primary diagnosis or recurrence
- •Not received prior systemic or local treatment (e.g., chemotherapy, endocrine or radiotherapy) for Stage IV/metastatic breast cancer
- •Prior adjuvant and/or neo-adjuvant therapy is permitted
- •Documentation of HER2 overexpression or gene amplification, in the invasive component of either a metastatic disease site or primary tumor, defined as: 3+ by IHC and/or HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization \[FISH, CISH or SISH; \>6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of ≥2.0\]
- •Documentation by the central laboratory of positive p95HER2 expression in the invasive component of either a metastatic disease site (preferred) or primary tumor
- •No history of CNS metastases (including leptomeningeal involvement) or stable CNS metastases (defined as asymptomatic and off steroids for ≥ 3 months)
- •Baseline Left Ventricular Ejection Fraction (LVEF) ≥50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA)
- •Recovered or stabilized from all adverse events associated with prior anti-cancer therapies, including radiotherapy, at the time of screening
Exclusion Criteria
- •History of other malignancy. Exception: Subjects who have been disease-free for 5 years or subjects with a history of completely resected non-melanoma skin cancer (basal or squamous) are eligible
- •Concurrent anti-cancer treatment or concurrent treatment with an investigational drug
- •Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment
- •Prior treatment with anti-HER2 therapy, except trastuzumab or lapatinib (time from last dose of trastuzumab or lapatinib to randomization must be ≥3 months)
- •Serious cardiac illness or medical condition including but not confined to:
- •Uncontrolled arrhythmias
- •Uncontrolled or symptomatic angina
- •History of congestive heart failure (CHF)
- •Documented myocardial infarction \<6 months from study entry
- •Current active hepatic or biliary disease (with exception of Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
Arms & Interventions
Lapatinib plus Chemotherapy
Lapatinib (1250mg once daily) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Intervention: Lapatinib
Lapatinib plus Chemotherapy
Lapatinib (1250mg once daily) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Intervention: Docetaxel
Lapatinib plus Chemotherapy
Lapatinib (1250mg once daily) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Intervention: Paclitaxel
Lapatinib plus Chemotherapy
Lapatinib (1250mg once daily) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Intervention: Vinorelbine
Trastuzumab plus Chemotherapy
Trastuzumab (either 6mg/kg q3-weekly or 2mg/kg weekly) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Intervention: Trastuzumab
Trastuzumab plus Chemotherapy
Trastuzumab (either 6mg/kg q3-weekly or 2mg/kg weekly) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Intervention: Docetaxel
Trastuzumab plus Chemotherapy
Trastuzumab (either 6mg/kg q3-weekly or 2mg/kg weekly) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Intervention: Paclitaxel
Trastuzumab plus Chemotherapy
Trastuzumab (either 6mg/kg q3-weekly or 2mg/kg weekly) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Intervention: Vinorelbine
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: Time from randomization to disease progression
Secondary Outcomes
- Overall Survival(end of study)
- Overall response rate (ORR: complete response [CR] or partial response [PR])(end of study)
- Clinical benefit response rate (CBR: CR or PR at any time, or stable disease [SD] >=24 weeks(end of study)
- Safety and tolerability of lapatinib plus chemotherapy and trastuzumab plus chemotherapy(end of study)