Breast Cancer
Conditions
Keywords
HR+/HER2- breast cancer, Palbociclib
Brief summary
This is a prospective, two arm, international, multicenter, randomized, open-label Phase III study evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR+ / HER2- early breast cancer (EBC). The purpose of the PALLAS study is to determine whether the addition of palbociclib to adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+/HER2- early breast cancer. Assessment of a variety of correlative analysis, including evaluation of the effect of palbociclib in genomically defined tumor subgroups, is planned.
Interventions
DRUGPalbociclib
Sponsors
Alliance Foundation Trials, LLC.
Austrian Breast & Colorectal Cancer Study Group
NSABP Foundation Inc
PrECOG, LLC.
Breast International Group
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent prior to study specific procedures. * Age ≥18 years (or per national guidelines). * Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000 patients) or Stage III early invasive breast cancer * Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER2-. * Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive breast cancer. * Patients must have undergone adequate (definitive) breast surgery for the current malignancy. FFPE tumor tissue block must be confirmed to be received at the central sample repository prior to randomization. * ECOG performance status 0-1. * Patients must be able and willing to swallow and retain oral medication. * Serum or urine pregnancy test must be negative in premenopausal women within 14 days of randomization, or in women with amenorrhea of less than 12 months at time of randomization. * Patients who received neo/adjuvant therapy must be after last dose of chemotherapy and/or biologic therapy and must have sufficient resolution of side effects. * Patients who received breast/axilla/post-mastectomy chest wall radiotherapy must be after last dose of radiotherapy and must have sufficient resolution of side effects. * Patients must have sufficient resolution of any surgical side effects (no active wound healing complications). -Patients must either be initiating or have already started adjuvant hormonal treatment. - * Patients who already received neo/adjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy. * Absolute neutrophil count ≥ 1,500/µL * Platelets ≥ 100,000/ mm3 * Hemoglobin ≥ 10g/dL * Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome. * Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN. * Serum creatinine below the upper limit of the institutional normal range (ULN) or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.
Exclusion criteria
* Concurrent therapy with other Investigational Products. * Prior therapy with any CDK inhibitor. * Patients with Stage I or IV breast cancer are not eligible. * History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib. * Patients receiving any medications or substances that are potent inhibitors or inducers of * CYP3A isoenzymes within 7 days of randomization. * Uncontrolled intercurrent illness that would limit compliance with study requirements. * Pregnant women, or women of childbearing potential without a negative pregnancy test within 14 days prior to randomization. * Patients with a history of any malignancy are ineligible * Patients who previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy. * Patients on antiretroviral therapy. * Patients with clinically significant history of any chronic liver disease. * Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease Free Survival (iDFS) | 4 years | Invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin. | 4 years | Invasive disease-free survival (iDFS, excluding second primary invasive cancers of non-breast origin) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS excluding second primary invasive cancers of non-breast origin is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. Second primary invasive cancers of non-breast origin will not be considered as events for this endpoint. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported. |
| Distant Recurrence-free Survival (DRFS) | 4 years | Compare time to distant recurrence-free survival (DRFS). Distant recurrence is defined according to STEEP criteria as the time from randomization to the date of the first event: distant recurrence or death from any cause. Patients with a locoregional recurrence will continue to be followed for DRFS. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, or death whichever came first. Direct comparison between arms used time to DRFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered DRFS at 4 years is reported. |
| Overall Survival (OS) | 4 years | Compare overall survival (OS). Overall survival is defined as the time period between randomization and death. Surviving patients classified as lost-to-follow up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first. |
| Locoregional Recurrences-free Survival (LRRFS) | 4 years | Compare locoregional recurrence-free survival (LRRFS). LRRFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, or death from any cause. Patients with second primary invasive cancers of non-breast origin or distant recurrence will be censored at the date of diagnosis. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first. |
Countries
Australia, Austria, Belgium, Canada, Germany, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATOREvanthia Galanis, MD
Alliance Foundation Trials, LLC.
PRINCIPAL_INVESTIGATORErica Mayer, MD
Dana-Farber Cancer Institute
PRINCIPAL_INVESTIGATORAngela DeMichele, MD
University of Pennsylvania
PRINCIPAL_INVESTIGATORMichael Gnant, MD
ABCSG, Medical University Vienna
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Palbociclib Plus Endocrine Therapy (Arm A) Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years. | 2,884 |
| Endocrine Therapy Alone (Arm B) Standard adjuvant endocrine therapy for a duration of at least 5 years. | 2,877 |
| Total | 5,761 |
Baseline characteristics
| Characteristic | Total | Endocrine Therapy Alone (Arm B) | Palbociclib Plus Endocrine Therapy (Arm A) |
|---|---|---|---|
| Age, Continuous | 52 years | 52 years | 52 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 265 Participants | 127 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5036 Participants | 2532 Participants | 2504 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 460 Participants | 218 Participants | 242 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 36 Participants | 22 Participants | 14 Participants |
| Race/Ethnicity, Customized Race Asain | 279 Participants | 141 Participants | 138 Participants |
| Race/Ethnicity, Customized Race Black or African American/African Heritage | 149 Participants | 75 Participants | 74 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or other Pacific Islander | 12 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Other | 73 Participants | 36 Participants | 37 Participants |
| Race/Ethnicity, Customized Race Unknown | 193 Participants | 97 Participants | 96 Participants |
| Race/Ethnicity, Customized Race White | 5019 Participants | 2498 Participants | 2521 Participants |
| Sex: Female, Male Female | 5725 Participants | 2858 Participants | 2867 Participants |
| Sex: Female, Male Male | 36 Participants | 19 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 99 / 2,841 | 76 / 2,902 |
| other Total, other adverse events | 2,824 / 2,841 | 2,600 / 2,902 |
| serious Total, serious adverse events | 369 / 2,841 | 229 / 2,902 |
Outcome results
Primary
Invasive Disease Free Survival (iDFS)
Invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.
Time frame: 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palbociclib Plus Endocrine Therapy (Arm A) | Invasive Disease Free Survival (iDFS) | 84.2 percentage of participants |
| Endocrine Therapy Alone (Arm B) | Invasive Disease Free Survival (iDFS) | 84.5 percentage of participants |
p-value: 0.6595% CI: [0.81, 1.14]Log Rank
Secondary
Distant Recurrence-free Survival (DRFS)
Compare time to distant recurrence-free survival (DRFS). Distant recurrence is defined according to STEEP criteria as the time from randomization to the date of the first event: distant recurrence or death from any cause. Patients with a locoregional recurrence will continue to be followed for DRFS. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, or death whichever came first. Direct comparison between arms used time to DRFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered DRFS at 4 years is reported.
Time frame: 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palbociclib Plus Endocrine Therapy (Arm A) | Distant Recurrence-free Survival (DRFS) | 86.2 percentage of patients |
| Endocrine Therapy Alone (Arm B) | Distant Recurrence-free Survival (DRFS) | 87.8 percentage of patients |
95% CI: [0.87, 1.28]
Secondary
Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin.
Invasive disease-free survival (iDFS, excluding second primary invasive cancers of non-breast origin) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS excluding second primary invasive cancers of non-breast origin is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. Second primary invasive cancers of non-breast origin will not be considered as events for this endpoint. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.
Time frame: 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palbociclib Plus Endocrine Therapy (Arm A) | Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin. | 85.4 percentage of patients |
| Endocrine Therapy Alone (Arm B) | Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin. | 86.0 percentage of patients |
95% CI: [0.82, 1.19]
Secondary
Locoregional Recurrences-free Survival (LRRFS)
Compare locoregional recurrence-free survival (LRRFS). LRRFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, or death from any cause. Patients with second primary invasive cancers of non-breast origin or distant recurrence will be censored at the date of diagnosis. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first.
Time frame: 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palbociclib Plus Endocrine Therapy (Arm A) | Locoregional Recurrences-free Survival (LRRFS) | 96.8 percentage of patients |
| Endocrine Therapy Alone (Arm B) | Locoregional Recurrences-free Survival (LRRFS) | 95.4 percentage of patients |
95% CI: [0.57, 1.23]
Secondary
Overall Survival (OS)
Compare overall survival (OS). Overall survival is defined as the time period between randomization and death. Surviving patients classified as lost-to-follow up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first.
Time frame: 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palbociclib Plus Endocrine Therapy (Arm A) | Overall Survival (OS) | 93.8 percentage of patients |
| Endocrine Therapy Alone (Arm B) | Overall Survival (OS) | 95.2 percentage of patients |
95% CI: [0.98, 1.78]