A Study to Compare the Safety and Efficacy of an Aromatase Inhibitor in Combination With Lapatinib, Trastuzumab or Both for the Treatment of Hormone Receptor Positive, HER2+ Metastatic Breast Cancer
- Conditions
- Neoplasms, Breast
- Interventions
- Registration Number
- NCT01160211
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
A study to compare the safety and efficacy of an aromatase inhibitor in combination with lapatinib, trastuzumab or both for the treatment of hormone receptor positive, HER2+ metastatic breast cancer (MBC).
- Detailed Description
This Phase III, multicenter, open-label study randomized subjects to one of the three treatment arms:
1. Treatment group A: lapatinib 1000 mg PO once daily + trastuzumab (loading dose of 8 mg/kg) followed by the maintenance dose of 6 mg/kg IV q3weeks + an AI (either letrozole, anastrozole, or exemestane) of Investigator's choice PO once daily.
2. Treatment group B: trastuzumab (loading dose of 8 mg/kg) followed by maintenance dose of 6 mg/kg IV q3weeks + an AI (either letrozole, anastrozole, or exemestane) of Investigator's choice PO once daily.
3. Treatment group C: lapatinib 1500 mg PO once daily + an AI (either letrozole, anastrozole, or exemestane) of Investigator's choice PO once daily.
Treatment continued until disease progression, death, or unacceptable toxicities, whichever came first.
Subjects who discontinued study treatment for reasons other than disease progression were followed-up every 12 weeks until disease progression or death, until the start of post-study treatment anti-cancer therapy (including radiotherapy and surgery), withdrawal of consent, or lost to follow-up, whichever came first.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 369
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment group A Lapatinib Lapatinib 1000 mg PO once daily + Trastuzumab (loading dose of 8 mg/kg) followed by the maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks) + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. Treatment group A Trastuzumab Lapatinib 1000 mg PO once daily + Trastuzumab (loading dose of 8 mg/kg) followed by the maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks) + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. Treatment group A Aromatase Inhibitor Lapatinib 1000 mg PO once daily + Trastuzumab (loading dose of 8 mg/kg) followed by the maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks) + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. Treatment group B Trastuzumab Trastuzumab (loading dose of 8 mg/kg) followed by maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks) + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. Treatment group B Aromatase Inhibitor Trastuzumab (loading dose of 8 mg/kg) followed by maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks) + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. Treatment Group C Aromatase Inhibitor Lapatinib 1500 mg PO once daily + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily. Treatment Group C Lapatinib Lapatinib 1500 mg PO once daily + an Aromatase Inhibitor (AI) of Investigator's choice PO once daily.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Events in Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) vs. Trastuzumab + Aromatase Inhibitor (AI) From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 5 years The Number of Participants with Progression free survival (PFS) events in the Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) arm vs. Trastuzumab + Aromatase Inhibitor (AI) arm was based on assessments by the Investigator.
Median Kaplan Meier Estimates for PFS in Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) vs. Trastuzumab + Aromatase Inhibitor (AI) From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 5 years Progression free survival (PFS) was defined as the interval of time between the date of randomization and the earliest date of disease progression (with radiological evidence) or death from any cause, or to the date of censor. Disease progression was based on assessments by the Investigator.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 11 years Progression free survival (PFS) was defined as the interval of time between the date of randomization and the earliest date of disease progression (with radiological evidence) or death from any cause, or to the date of censor. Disease progression was based on assessments by the Investigator.
Overall Survival (OS) From date of randomization until date of death from any cause, assessed up approximately 11 years The Number of Participants with Overall Survival (OS) events was based on assessments by the Investigator.
Overall Response Rate (ORR) Up approximately 11 years Overall Response Rate (ORR) was defined as the proportion of participants achieving either a Complete Response (CR) or Partial Response (PR). The ORR was calculated from the Investigator's assessment of response based on RECIST 1.1. Subjects with an unknown or missing response were treated as non-responders; i.e. they were included in the denominator when calculating the percentages. Subjects who do not have measurable disease contributed to the Response Rate based analyses, for the evaluation of CR, SD and PD.
Clinical Benefit Rate (CBR) Up approximately 11 years Clinical Benefit Rate (CBR) was defined as the percentage of patients with evidence of Complete Response (CR), Partial Response (PR), or maintaining Stable Disease (SD) for at least 6 months while on study, according to the investigator assessment of response per RECIST 1.1 criteria.
Time to Response From date of randomization until the earliest date of Complete Response (CR) or Partial Response (PR), assessed up approximately 11 years Time to Response (TTR) was defined as the time from randomization to the earliest date of Complete Response (CR) or Partial Response (PR)
Duration of Response (DoR) From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up approximately 11 years Duration of Response (DOR) was defined as the duration between the date of first documented Complete Response (CR) or Partial Response (PR) and the date of first documented sign of Progressive Disease or Death, or to the date of censor.
Mean Change in the Quality of Life (QoL) Status Relative to Baseline FACT-B Overall and Subscale Scores at Last On Treatment Assessment Day 1 (pre-dose), up approximately 11 years Quality of life was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. It is a 37-item (27 general questions and 10 breast cancer specific questions) self-reporting instrument consisting of 5 dimensions: physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and a breast cancer subscale (BCS). The followings were the score ranges for each self-reporting subscale: • PWB : 0-28 • SWB : 0-28 • EWB : 0-24 • FWB : 0-28 • BCS : 0-40 FACT-B Total Outcome Index (TOI) = PWB + FWB + BCS (range:0 - 96) FACT-B Total Score = PWB + SWB + EWB + FWB + BCS (range:0-148) FACT-G Total Score = PWB + SWB + EWB + FWB (range:0-108). For all the FACIT scales and symptom indices, the higher the score the better QoL
Trial Locations
- Locations (1)
Novartis Investigative Site
🇬🇧Peterborough, United Kingdom