Breast Cancer
Conditions
Keywords
human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), HER2-negative, HR-Positive, Breast Cancer (BC), Neoadjuvant, Postmenopausal
Brief summary
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.
Interventions
DRUGPF-07220060
PF-07220060 given as tablet by mouth twice a day for 14 days.
DRUGletrozole
Letrozole given as tablet by mouth once a day for 14 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 1. * 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Cell Cycle Arrest (CCCA) at Day 14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity and was congenital anomaly/birth defect. AEs that occurred on or after the first dose of study treatment and before the end of treatment (35 days after last dose of study treatment or start of subsequent anti-cancer therapy minus 1 day, whichever occurred first) was considered TEAEs. All AEs (SAEs and all other AEs) were considered for evaluation. |
| 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) | An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity and was congenital anomaly/birth defect. AEs that occurred on or after the first dose of study treatment and before the end of treatment (35 days after last dose of study treatment or start of subsequent anti-cancer therapy minus 1 day, whichever occurred first) was considered TEAEs. |
| Number of Participant With AEs Leading to Any Study Intervention Discontinuation | During study treatment (maximum up to 14 days) | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| 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) | The methylation-based tumor fraction of a single sample was estimated from methylation signals across targeted regions from the methylation panel, was calibrated using training data including cancer free donors and participants with mixed cancer types. The method included a data-informed differentially methylated region selection targeting regions with high pan cancer signal to noise ratio. This value was an estimate of the proportion of the sample that was tumor derived and expressed as percentage of DNA. ctDNA methylation tumor fraction values were reported in percentage at Baseline and Day 14 were assessed from central laboratory. |
| Plasma Concentration (Ctrough) of PF-07220060 on Day 14 | Pre-dose (within 30 minutes before dosing) on Day 14 | Ctrough was pre-dose plasma concentration. |
| 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 | Cperi-biopsy was plasma concentration at the time of biopsy. |
| 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) | Ki-67 was extensively used as a prognostic and predictive biomarker for cancer diagnosis and treatment. Ki-67 expression was measured by immunohistochemistry and expressed as percentage of cells. Assessment at baseline and Day 14 was done in blinded manner by centrally assessed biopsy. |
| 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) | 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 baseline and Day 14 was done in blinded manner by centrally assessed biopsy. Relative reduction at Day 14 was calculated as:100 \*(1-Ki-67 at Day 14/Ki-67 at Baseline). Relative reduction was expressed in percentage reduction. |
Countries
Australia, Belgium, France, Germany, Italy, Poland, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 66.5 Years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants |
| Race (NIH/OMB) White | 90 Participants |
| Sex: Female, Male Female | 121 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 62 |
| other Total, other adverse events | 21 / 59 | 16 / 62 |
| serious Total, serious adverse events | 1 / 59 | 0 / 62 |
Outcome results
None listed