Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer
- Conditions
- Estrogen Receptor Positive Breast CancerHER-2 Positive Breast Cancer
- Interventions
- Registration Number
- NCT02947685
- Lead Sponsor
- Alliance Foundation Trials, LLC.
- Brief Summary
The primary objective of this study is to demonstrate that the combination of palbociclib with anti-HER2 therapy plus endocrine therapy is superior to anti-HER2-based therapy plus endocrine therapy alone in improving the outcomes of subjects with hormone receptor-positive, HER2+ metastatic breast cancer.
- Detailed Description
Subjects will be randomized into one of two treatment arms following minimum of 4 and maximum of 8 cycles of induction treatment with anti-HER2 therapy. Arm A subjects will receive the experimental therapy, palbociclib, in addition to their current anti-HER2 therapy and endocrine therapy. Arm B subjects will continue to receive the anti-HER2 therapy. It is expected that the addition of palbociclib to the first-line treatment of HER2 disease will delay the onset of therapeutic resistance and ultimately prolong the survival of patients with metastatic breast cancer. The study is designed to treat the subset of patients with HER2+ disease who are also hormone receptor positive (HR+). It is also expected that palbociclib will modulate the endocrine resistance in HER2+/HR+ disease and potentiate the benefits of anti-HER2 therapy. Lastly, the current study includes a comprehensive molecular characterization of the disease at study entrance which will allow us to investigate the benefits of palbociclib in subsets of HER2+/HR+ disease such as PIK3CA mutant.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 518
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A palbociclib Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression Arm B Anastrozole AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression Arm B Fulvestrant AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression Arm A pertuzumab Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression Arm A trastuzumab Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression Arm A letrozole Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression Arm B pertuzumab AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression Arm A Anastrozole Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression Arm A Exemestane Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression Arm B letrozole AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression Arm A Fulvestrant Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression Arm B Exemestane AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) as assessed by Investigator 24 months
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) 24 months Defined as time from date of randomization to date of death due to any cause
Objective Response Rate (OR: CR or PR) 24 months Defined as complete response (CR) or partial response (PR) according to RECIST v1.1
Duration of Response (DOR) 24 months Defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death from any cause, whichever occurs first
Safety: Type incidence and severity (as graded by NCI CTCAE v 4.0) 24 months Seriousness and attribution to the study medications of AEs and any laboratory abnormalities
3 and 5 year survival probabilities 24 months Survival probabilities will be estimated using the Kaplan-Meier method
Incidence of CNS Metastasis 24 months Compare the incidence of CNS metastasis between treatment arms
Clinical Benefit Rate (CBR: CR or PR or SD ≥ 24 weeks 24 months The Clinical Benefit Rate (CBR) on each treatment arm will be estimated by dividing the number of patients with CR, PR, or SD/Non-CR and Non-PD (for patients with measurable disease) ≥ 24 weeks by the number of patients randomized to the treatment arm.
Patient Reported Outcomes 24 months Time to symptom progression (FACT-B PFB-TOI), breast cancer specific health treatment related quality of life and general health status
Trial Locations
- Locations (106)
UCSF
🇺🇸San Francisco, California, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Baycare Healthcare (Morton Plant Mease)
🇺🇸Clearwater, Florida, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Scroll for more (96 remaining)UCSF🇺🇸San Francisco, California, United States