Advanced Breast Cancer Female
Conditions
Keywords
palbociclib, ibrance, breast cancer
Brief summary
The purpose of this study is to provide access to palbociclib in Mexico and in selected Latin American countries before it becomes commercially available to patients with HR positive/HER2-negative ABC who are appropriate candidates for letrozole therapy.
Interventions
DRUGPalbociclib
Palbociclib will be administered orally once a day at 125 mg/day for 21 days followed by 7 days off treatment for each 28-day cycle (Schedule 3/1).
DRUGLetrozole
Letrozole will be administered orally at 2.5 mg once daily as continuous daily dosing schedule according to product labeling and in compliance with its local prescribing information.
Sponsors
Pfizer
Study design
Allocation
NA
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult women with proven diagnosis of advanced adenocarcinoma of the breast (locoregional recurrent or metastatic disease). * Women who are not of childbearing potential. * ER-positive and/or Progesterone receptor (PgR)-positive tumor based on local laboratory results (test as per local practice). * HER2-negative breast cancer based on local laboratory results (test as per local practice or local guidelines). * Patients must be appropriate candidates for letrozole therapy. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Adequate bone marrow function. * Adequate liver function * Adequate renal function.
Exclusion criteria
* Known hypersensitivity to letrozole, or any of its excipients, or to any palbociclib excipients. * Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4 isoenzymes within 7 days prior to study entry. * Prior treatment with any CDK inhibitor. * Previous participation in a palbociclib clinical study. * Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation. * QTc \>480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes. * High cardiovascular risk, including, but not limited to recent myocardial infarction, severe/unstable angina and severe cardiac dysrhythmias in the past 6 months prior to enrollment. * Diagnosis of any second invasive malignancy within the last 3 years prior to enrollment. Note: patients with adequately treated basal cell or squamous cell skin cancer, a history of intraepithelial neoplasia or in situ disease (eg, carcinoma in situ of the cervix or melanoma in situ) may enter. * Active uncontrolled or symptomatic brain metastases. Previously treated and clinically stable, brain metastases are permitted. * Other severe acute or chronic medical or psychiatric conditions. * Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees directly involved in the conduct of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs) | 3 years | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. |
| Number of Participants With Palbociclib-related TEAEs | 3 years | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to CTCAE version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Palbociclib-related TEAEs were determined by the investigator. |
| Number of Participants With Serious Adverse Events (SAEs) | 3 years | An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. Palbociclib-related SAEs were determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Death | 3 years | Death from any cause while on treatment and within 28 days of palbociclib discontinuation was only counted below. |
| The Objective Response Rate (ORR) | 3 years | The tumor response was based on the response reported by investigator per local practice. No response confirmation was applied. ORR was defined as the percentage of participants with complete response or partial response relative to all as-treated population. |
Countries
Argentina, Brazil, Colombia, Mexico
Participant flow
Pre-assignment details
A total of 131 participants were enrolled and assigned to study treatment, and 130 participants were treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Palbociclib+Letrozole Participants received palbociclib orally once daily at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle, and letrozole orally at 2.5 mg QD as a continuous daily dosing schedule. Participants continued to receive treatments with palbociclib+letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, withdrawal of consent, or time of commercial availability of palbociclib, whichever occurred first. | 130 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 10 |
| Overall Study | Global deterioration of health status | 2 |
| Overall Study | Insufficient clinical response | 6 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Not treated | 1 |
| Overall Study | Objective progression or relapse | 50 |
| Overall Study | Study terminated by Sponsor | 53 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Palbociclib+Letrozole |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 41 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 130 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 130 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 130 |
| other Total, other adverse events | 129 / 130 |
| serious Total, serious adverse events | 32 / 130 |
Outcome results
Primary
Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity.
Time frame: 3 years
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib+Letrozole | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs) | Grade 1 | 0 Participants |
| Palbociclib+Letrozole | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs) | Grade 2 | 17 Participants |
| Palbociclib+Letrozole | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs) | Grade 3 | 82 Participants |
| Palbociclib+Letrozole | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs) | Grade 4 | 23 Participants |
| Palbociclib+Letrozole | Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs) | Grade 5 | 7 Participants |
Primary
Number of Participants With Palbociclib-related TEAEs
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to CTCAE version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Palbociclib-related TEAEs were determined by the investigator.
Time frame: 3 years
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib+Letrozole | Number of Participants With Palbociclib-related TEAEs | Grade 1 | 2 Participants |
| Palbociclib+Letrozole | Number of Participants With Palbociclib-related TEAEs | Grade 2 | 25 Participants |
| Palbociclib+Letrozole | Number of Participants With Palbociclib-related TEAEs | Grade 3 | 81 Participants |
| Palbociclib+Letrozole | Number of Participants With Palbociclib-related TEAEs | Grade 4 | 20 Participants |
| Palbociclib+Letrozole | Number of Participants With Palbociclib-related TEAEs | Grade 5 | 0 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs)
An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. Palbociclib-related SAEs were determined by the investigator.
Time frame: 3 years
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib+Letrozole | Number of Participants With Serious Adverse Events (SAEs) | All-causality | 32 Participants |
| Palbociclib+Letrozole | Number of Participants With Serious Adverse Events (SAEs) | Palbociclib-related | 6 Participants |
Secondary
Number of Participants With Death
Death from any cause while on treatment and within 28 days of palbociclib discontinuation was only counted below.
Time frame: 3 years
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Palbociclib+Letrozole | Number of Participants With Death | 5 Participants |
Secondary
The Objective Response Rate (ORR)
The tumor response was based on the response reported by investigator per local practice. No response confirmation was applied. ORR was defined as the percentage of participants with complete response or partial response relative to all as-treated population.
Time frame: 3 years
Population: The analysis population included participants with efficacy data contributing to the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palbociclib+Letrozole | The Objective Response Rate (ORR) | 24.8 percentage of evaluable participants |