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
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 5,796
- 试验地点
- 437
- 主要终点
- Invasive Disease Free Survival (iDFS)
研究概览
简要总结
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.
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
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: Palbociclib (Drug)
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.
干预措施: Standard Adjuvant Endocrine Therapy (Drug)
Arm B
Standard adjuvant endocrine therapy for a duration of at least 5 years.
干预措施: Standard Adjuvant Endocrine Therapy (Drug)
结局指标
主要结局
Invasive Disease Free Survival (iDFS)
时间窗: 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.
次要结局
- 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)