Study of Poziotinib in Participants With HER2-Positive Metastatic Breast Cancer
- Registration Number
- NCT02659514
- Lead Sponsor
- Spectrum Pharmaceuticals, Inc
- Brief Summary
The purpose of this study is to establish the dose regimen and evaluate the preliminary efficacy and the safety/tolerability of poziotinib in participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have received at least two prior HER2-directed treatment regimens.
- Detailed Description
This is a phase 2, open-label, multicenter study to establish the dose regimen and evaluate the preliminary efficacy and the safety/tolerability of poziotinib in participants with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed treatment regimens.
Each treatment cycle will be 21 days in duration. During each 21-day cycle, participants who are eligible for participation will receive poziotinib orally once daily.
All treated participants will be followed up until disease progression, death, intolerable adverse events or up to a maximum of 24 months whichever comes earlier.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 67
- Histopathologically confirmed primary breast cancer with metastatic lesions.
- Confirmed HER2 overexpression or gene-amplified tumor
- At least two prior HER2-directed therapy regimens for breast cancer, including trastuzumab and trastuzumab emtansine
- Measurable disease per Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1)
- Participant is at least 18, and ≤90 years of age.
- Adequate hematologic, hepatic, and renal function
- Eastern Cooperative Oncology Group (ECOG) performance status <= 2
- Previous treatment with poziotinib prior to study participation
- Brain metastases that are symptomatic or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 15 days of enrollment.
- Anticancer chemotherapy, biologics, immunotherapy, cure-intent radiotherapy, or investigational treatment within 15 days, except for hormone therapy, palliative therapy, or supportive therapy.
- History of congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
- Cardiac ejection fraction <50%
- History of other malignancies within the last 5 years
- Participant is pregnant or breast-feeding.
- Unable to take drugs orally
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: Poziotinib 24 mg Poziotinib Participants received poziotinib 24 milligrams (mg), administered as three 8 mg tablets, orally, once daily (QD) on an intermittent dosing schedule of 14 days on treatment followed by 7 days off treatment, in a 21-day cycle until disease progression, death, intolerable adverse events (AEs) or for up to a maximum of 24 months, whichever occurs first. Cohort 2: Poziotinib 16 mg Poziotinib Participants received poziotinib 16 mg, administered as two 8 mg tablets, orally, QD, on a continuous dosing schedule in a 21-day cycle until disease progression, death, intolerable AEs or for up to a maximum of 24 months, whichever occurs first.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to 24 months ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) among participants in the Evaluable Population assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR was based on investigator assessed BOR. Per RECIST v1.1 for target lesions, CR was disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis \<10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (PD) (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm).
- Secondary Outcome Measures
Name Time Method Time to Progression (TTP) Up to 24 months TTP was defined as the time (in months) from first administration of study drug to tumor progression, which excluded death without tumor progression, by the end of study. TTP of participants who died without documented PD was censored at date of death. TTP of living participants without documented PD was censored at the same time as PFS, which was the last tumor assessment or the date of first treatment if there was no post-baseline tumor assessment. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm.
Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) From the first dose of study drug administration until 35 (± 5) days after the last dose of study drug administration (Up to approximately 25 months) An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were AEs that occurred or worsened from the first dose of study treatment until 35 (± 5) days after the last dose of study treatment.
Pharmacokinetic Analysis (Drug Concentration Measurements) For Cohort 1: Pre-dose and 1 and 2 hours post-dose on Day 1 of Cycles 1, 2, and 3, and pre-dose on Day 14 of Cycle 1 For Cohort 2: Day 1 of Cycle 1 pre-dose and 30 minutes, 1,1.5,2,3, 4, 6, and 24 hours post-dose of Day 1 of Cycle 1 Progression Free Survival (PFS) Up to 24 Months PFS was the duration of time (in months) from first administration of study treatment to date of first documented disease progression or death from any cause. PFS of living participants without documented PD was censored at the time of last tumor assessment or the date of first treatment if there was no post-baseline tumor assessment. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm.
Disease Control Rate (DCR) Up to 24 months DCR was the percentage of participants whose best response was CR, PR or stable disease (SD) among participants in the Evaluable Population assessed per RECIST v1.1. DCR was based on investigator-assessed BOR. Per RECIST v1.1 for target lesions, CR was defined as disappearance of all target TLs and all target LNs with short axis \<10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm). SD was SOD change neither sufficient for PR nor sufficient for PD.
Duration of Response (DoR) Up to 24 months DoR was evaluated only for participants whose BOR was CR or PR and was defined as the time (in months) from the date that response evaluation criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that PD or death was documented. DoR of participants without documented PD or death was censored at the time of last tumor assessment. Per RECIST v1.1 for target lesions, CR was defined as disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis \<10mm. PR was defined as ≥30% decrease in sum of diameters (SOD) from Baseline, and not PD. PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm).
Trial Locations
- Locations (35)
Clearview Cancer Center
🇺🇸Huntsville, Alabama, United States
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
Marin Cancer Care, Inc
🇺🇸Greenbrae, California, United States
PacificShores Medical Group
🇺🇸Long Beach, California, United States
Valley Medical Oncology Consultants
🇺🇸Pleasanton, California, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
AMPM Research Clinic
🇺🇸Miami Gardens, Florida, United States
FL Cancer Research Institute
🇺🇸Plantation, Florida, United States
Bond Clinic, P.A.
🇺🇸Winter Haven, Florida, United States
Triple Army Medical Cente
🇺🇸Honolulu, Hawaii, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
North Shore Hematology Oncology Associates
🇺🇸East Setauket, New York, United States
Hudson Valley Hematology Oncology Associates
🇺🇸Poughkeepsie, New York, United States
White Plain Hospital
🇺🇸White Plains, New York, United States
Aultman Hospital
🇺🇸Canton, Ohio, United States
Oklahoma Cancer Specialists & Research Institute, LLC
🇺🇸Tulsa, Oklahoma, United States
Carolina Blood and Cancer Care Associates PA
🇺🇸Rock Hill, South Carolina, United States
Texas Oncology-McAllen
🇺🇸McAllen, Texas, United States
Scott & White Memorial Hospital
🇺🇸Temple, Texas, United States
Providence Regional Cancer System
🇺🇸Lacey, Washington, United States
Medical Oncology Associates, PS
🇺🇸Spokane, Washington, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Northwest Medical Specialties, PLLC
🇺🇸Tacoma, Washington, United States
Waverly Hematology Oncology
🇺🇸Cary, North Carolina, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Alliance Research Centers
🇺🇸Laguna Hills, California, United States
The University of Kansas Cancer Center and Medical Pavilion
🇺🇸Westwood, Kansas, United States
Franciscan St. Francis Health
🇺🇸Indianapolis, Indiana, United States
Hattiesburg Clinic Hematology Oncology
🇺🇸Hattiesburg, Mississippi, United States
Oncology Consultants, P.A.
🇺🇸Houston, Texas, United States
Magee Womens Hospital of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
The University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Charleston Cancer Center
🇺🇸Charleston, South Carolina, United States
SAMMC - Hem/Onc Clinic
🇺🇸Houston, Texas, United States