PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer
Overview
- Phase
- Phase 3
- Intervention
- Palbociclib
- Conditions
- Breast Cancer
- Sponsor
- Alliance Foundation Trials, LLC.
- Enrollment
- 5796
- Locations
- 437
- Primary Endpoint
- Invasive Disease Free Survival (iDFS)
- Status
- Active, not recruiting
- Last Updated
- 2 months ago
Overview
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.
Investigators
Eligibility Criteria
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-
- •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.
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.
Arms & Interventions
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.
Intervention: Palbociclib
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.
Intervention: Standard Adjuvant Endocrine Therapy
Arm B
Standard adjuvant endocrine therapy for a duration of at least 5 years.
Intervention: Standard Adjuvant Endocrine Therapy
Outcomes
Primary Outcomes
Invasive Disease Free Survival (iDFS)
Time Frame: 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 Outcomes
- Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin.(4 years)
- Distant Recurrence-free Survival (DRFS)(4 years)
- Overall Survival (OS)(4 years)
- Locoregional Recurrences-free Survival (LRRFS)(4 years)