Clinical trial NCT04247633: High Risk ER+HER2- T1-2N0-1 Early Breast Cancer With Palbociclib Plus Endocrine Therapy(HIPEx)
Official title: Single-arm Phase II Study of Palbociclib Plus Endocrine Therapy in Patients With High Risk ER-positive/HER2-negative T1-2N0-1 Early Breast Cancer Incorporating GenesWell™ BCT
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Korean Cancer Study Group
First posted: 2020-01-30
Enrollment: 578
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II, multi-center, single-arm, open-label trial to evaluate efficacy of palbociclib with endocrine therapy as adjuvant treatment in women with C-high/G-high risk ER-positive/HER2-negative T1-2N0-1 EBC(Early Breast Cancer)

Detailed description: The investigators hypothesized that the GenesWell™ BCT may help inform decision about whether or not to have adjuvant chemotherapy to patients with high-risk pN0-N1, ER+/HER2- breast cancer in Korea. While adjuvant therapy for ER-positive EBC is effective in reducing risk of recurrence and improving survival, recurrences are still common, especially in patients with unfavorable factors in terms of clinical, pathological and/or molecular perspectives.

Since the addition of CDK4/6 inhibitor, palbociclib, to endocrine therapy (ET) has proven clinical efficacy with tolerable toxicity profile in ER-positive, HER2-negative advanced BC, its use in the adjuvant setting may decrease risk of recurrences in patients with ER-positive, HER2-negative EBC after surgical resection of the primary tumor by enhancing primary endocrine responsiveness and preventing, or delaying the development of acquired resistance for endocrine therapy.

The purpose of this study is to evaluate the effect of addition of palbociclib to standard adjuvant ET on event-free survival (EFS) in patients with ER-positive, HER2-negative EBC but unfavorable clinicopathological (clinical high risk, C-high) and molecular features (genomic high risk, G-high).

Eligibility criteria: Inclusion Criteria:

1. Patient is an adult, ≥ 19 years old at the time of informed consent
2. Premenopausal and postmenopausal women or men with invasive breast cancer
3. De novo primary disease
4. Patient who performed surgery with curative aim
5. Patient who has negative surgical resection margins
6. Patient with histologically confirmed HER2-negative breast cancer
7. Patient with histologically and cytologically confirmed ER positive breast cancer by local laboratory testing
8. Pathological node assessment: pN0 or pN1
9. Tumor size ≥ 0.5 cm, and T1 or T2
10. Clinical High-Risk (Clinical high-risk patients as per the modified Adjuvant! Online guideline in the clinical trial MINADCT(Microarray in Node Negative Disease May Avoid Chemotherapy), refer to section 5.2.1)
11. Genomic High-Risk in BCT score (≥ 4)
12. Patients agreed to use effective contraception or not be of childbearing potential.
13. Patient has adequate bone marrow and organ function
14. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
15. Patient who is able to swallow and retain oral medication
16. A FFPE tumor sample must be available for inclusion. The tumor sample must be taken from the excised primary tumor

Exclusion Criteria:

1. Patient with recurred breast cancer
2. Patient with histologically confirmed ER negative
3. Patient with histologically confirmed HER2-positive
4. Pathological node assessment: pN2 or pN3
5. Patients has received neoadjuvant chemotherapy or endocrine therapy
6. Patient has received preoperative treatment with CDK 4/6 inhibitors.
7. Patient has received preoperative radiation therapy
8. Tumor size less than 0.5 cm
9. Patients with low clinical risk group (section 5.2.1)
10. Patients who low BCT risk group (BCT score\<4)
11. Patients with lactose intolerance
12. Patients with a hypersensitivity to IP and/or components of IP
13. Pregnant women, women of childbearing potential or lactating women
14. Patients who have serious underlying co-morbidities which could cause end-organ dysfunction
15. A FFPE tumor sample is not available

Primary outcomes:
measure: 3-year event-free survival
timeFrame: up to 3 years
Secondary outcomes:
measure: overall survival
timeFrame: up to 5 years
measure: Prognostic and predictive effects of BCT
timeFrame: up to 5 years
measure: Adverse Events
timeFrame: up to 2 years
measure: Quality of Life (QoL)
timeFrame: up to 5 years
measure: Exploratory analysis of genomic biomarkers
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: