AN INTERVENTIONAL, OPEN-LABEL, RANDOMIZED, MULTICENTER, PHASE 2 STUDY OF PF-07220060 PLUS LETROZOLE COMPARED TO LETROZOLE ALONE IN POSTMENOPAUSAL WOMEN 18 YEARS OR OLDER WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER IN THE NEOADJUVANT SETTING
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 121
- 试验地点
- 100
- 主要终点
- Rate of Ki-67
研究概览
简要总结
The purpose of this study is to learn about the effects of the study medicine PF-07220060 plus letrozole, compared with the effects of taking letrozole alone without PF-07220060 for treatment of breast cancer.
This study is seeking for participants who are:
- women of age 18 years and older post menopause (either naturally or surgically).
- confirmed to have Hormone receptor (HR) positive, Human epidermal growth factor receptor 2 (HER2) negative breast cancer. HER2 negative describes cells that have a small amount or none of a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that are HER2 negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface.
- not been treated for their cancer before this study.
Participants will be randomly assigned (like flipping a coin) to receive the treatment (PF-07220060 plus letrozole) or letrozole alone. Both PF-07220060 and letrozole are taken by mouth. PF-07220060 will be taken twice a day for 14 days. Letrozole will be taken once a day for 14 days.
Participants will have a screening period for up to 28 days. If deemed fit, they will receive study treatment for 14 days, and then will have a follow-up visit about 28 days after their last dose.
All participants will have at least one biopsy during the study. Biopsy is the removal of cells or tissues for examining. All participants will have a biopsy on Day 14.
Additional assessments for safety including blood draws and interviews done by the site staff will be completed during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal women with histologically confirmed HR-positive and HER2-negative BC (per local assessment)
- •Documented by estrogen receptor (ER) and/or progesterone receptor (PR)-positive disease by IHC or ISH
- •Participants must have Ki-67 score >/=10% with unilateral, invasive T1c-T4c, N0-N2, M0 BC
- •Participants must be willing and able to undergo a baseline and Day 14 biopsy and must have an ECOG PS or 0 or
- •Participants must be treatment naive for the treatment of BC and cannot have had prior treatment with any systemic therapy (e.g., chemotherapy, hormonal therapy), radiation, surgery, or any investigational agents or use of hormone replacement therapy (HRT) or any other estrogen-containing medication (including vaginal estrogen) within 2 weeks prior to diagnostic tissue sample taken.
排除标准
- •No prior systemic therapy, radiation, surgery, investigational therapy for treatment of breast cancer
- •Certain medical conditions in the previous 6 months, for example: myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism or other clinically significant episode of thromboembolism
- •Lab abnormalities outside protocol specified parameters
研究组 & 干预措施
Arm A/Experimental/PF-07220060 plus letrozole
PF-07220060 given as tablet by mouth twice a day for 14 days. Letrozole given as tablet by mouth once a day for 14 days.
干预措施: PF-07220060 (Drug)
Arm B/Control/letrozole
Letrozole given by mouth once a day for 14 days.
干预措施: letrozole (Drug)
Arm A/Experimental/PF-07220060 plus letrozole
PF-07220060 given as tablet by mouth twice a day for 14 days. Letrozole given as tablet by mouth once a day for 14 days.
干预措施: letrozole (Drug)
结局指标
主要结局
Rate of Ki-67
时间窗: Day 14
Centrally assessed biopsy
Percentage of Participants With Complete Cell Cycle Arrest (CCCA) at Day 14
时间窗: Day 14
CCCA was determined by antigen Kiel 67 (Ki-67) value as decided by Sponsor. Ki-67 was extensively used as a prognostic and predictive biomarker for cancer diagnosis and treatment. Ki-67 expression was measured by immunohistochemistry. Assessment at Day 14 was done in blinded manner by centrally assessed biopsy.
次要结局
- Circulating tumor DNA (ctDNA) measurements(Baseline and Day 14)
- Incidence of Adverse Events (AEs)(Baseline, Day 14, and Day 28 post last treatment follow-up visit)
- Incidence of Serious AEs(Baseline, Day 14, and Day 28 post last treatment follow-up visit)
- Incidence of AEs leading to Discontinuation(Baseline, Day 14, and Day 28 post last treatment follow-up visit)
- Ctrough and peri-biopsy plasma concentrations of PF-07220060(Pre-dose within 30 minutes and post-dose within 1 hour before or after biopsy)
- Percentage of Ki-67(Screening and Day 14)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From start of study intervention (Day 1) up to 35 days after the last dose of study intervention or start of subsequent anti-cancer therapy minus 1 day, whichever occurred first (approximately up to 49 days))
- Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)(From start of study intervention (Day 1) up to 35 days after the last dose of study intervention or start of subsequent anti-cancer therapy minus 1 day, whichever occurred first (approximately up to 49 days))
- Number of Participant With AEs Leading to Any Study Intervention Discontinuation(During study treatment (maximum up to 14 days))
- Circulating Tumor Deoxyribonucleic Acid (ctDNA) Methylation Tumor Fraction Values at Baseline and Day 14(Baseline (the last measurement on or prior to date of the first dose of study intervention if the first dose is not missing, otherwise, on or prior to the randomization date), Day 14 (pre-dose))
- Plasma Concentration (Ctrough) of PF-07220060 on Day 14(Pre-dose (within 30 minutes before dosing) on Day 14)
- Plasma Concentration at the Time of Biopsy (Cperi-biopsy) of PF-07220060 on Day 14(Within 1 hour before or 1 hour after biopsy on Day 14)
- Change From Baseline in Antigen Ki-67 at Day 14(Baseline (the last measurement on or prior to date of the first dose of study intervention if the first dose was not missing, otherwise, on or prior to the randomization date), Day 14 (pre-dose))
- Relative Reduction (%) of Ki-67 From Baseline at Day 14(Baseline (the last measurement on or prior to date of the first dose of study intervention if the first dose was not missing, otherwise, on or prior to the randomization date), Day 14 (pre-dose))