Adjuvant Intensification for LAR

Official title

Standard Chemotherapy Plus Oral Everolimus as Adjuvant Therapy for LAR Breast Cancer Patients: A Randomized, Open-Label, Phase III Trial （POLARIS）

Overview

This study enrolled patients with early-stage triple-negative breast cancer who had undergone radical surgery. The postoperative pathology met the TNM staging criteria of pT1c-3N0-3M0, and immunohistochemistry (IHC) results confirmed ER-negative status (IHC showed \<1% of tumor cells positive for ER), PR-negative status (IHC showed \<1% of tumor cells positive for PR), and HER2-negative status (IHC intensity of 0 or 1+; or IHC intensity of 2+ but with negative in situ hybridization results). Additionally, patients either exhibited high AR expression (IHC showing AR ≥10%) or were classified as the LAR subtype based on digital pathology. This study plans to prospectively enroll 904 subjects, who will be randomized in a 1:1 ratio after completing standard chemotherapy. They will be allocated to either the standard-of-care (SOC) chemotherapy followed by everolimus group or the SOC-alone group. The study aims to evaluate the efficacy of SOC chemotherapy followed by everolimus versus SOC chemotherapy alone as adjuvant therapy for patients with early-stage radically resected triple-negative breast cancer of the LAR subtype, with the primary endpoint being 3-year invasive disease-free survival (iDFS).

Interventions

• Drug Everolimus 10 mg daily
  After completion of standard chemotherapy, everolimus at a fixed dose of 10 mg orally once daily continuously for a duration of 1 year.

Primary outcome measures

• iDFS [Time frame: 3 year]

Secondary outcome measures (6)

• DFS [Time frame: 3 year]
• DDFS [Time frame: 3year]
• RFS [Time frame: 3 year]
• OS [Time frame: 3 year]
• Safety and Tolerability [Time frame: 3 year]
• Quality of Life score in the per-protocol population [Time frame: 3 year]

Eligibility criteria

Inclusion criteria

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Patients must meet \*\*all\*\* of the following inclusion criteria to be enrolled in this study:

• Female, aged ≥18 years and ≤70 years.
• ECOG performance status 0-1.
• Histologically confirmed invasive triple-negative breast cancer (\*\*definition\*\*: breast cancer with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) all confirmed negative by pathology. Specifically: \*\*ER-negative\*\*: IHC <1%; \*\*PR-negative\*\*: IHC <1%; \*\*HER2-negative\*\*: IHC 0/1+ or IHC 2+ but FISH/CISH negative. Additionally, histology must confirm \*\*high AR expression\*\*: AR IHC ≥10%, \*\*or\*\* digital pathology indicates the LAR subtype.
• Underwent radical surgery for early-stage breast cancer, with postoperative pathology meeting TNM staging \*\*pT1c-3N0-3M0\*\*.
• Patients with early-stage breast cancer who have received \*\*at least 4 cycles of neoadjuvant chemotherapy containing anthracycline or taxane agents\*\*, \*\*did not achieve pathological complete response (pCR)\*\*, and \*\*do not carry pathogenic/likely pathogenic germline BRCA1/2 mutations\*\*.
• Adequate organ function, meeting the following criteria:

• \*\*Hematology\*\*: HB ≥ 90 g/L (no transfusion within 14 days); ANC ≥ 1.5 × 10⁹/L; PLT ≥ 75 × 10⁹/L.

• \*\*Biochemistry\*\*: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; serum Cr ≤ 1 × ULN, with creatinine clearance >50 mL/min (Cockcroft-Gault formula).
• Surgical wound fully healed before study initiation.
• Females of childbearing potential must use a medically approved contraceptive method during the study treatment and for at least 3 months after the last dose of study drug.
• The patient voluntarily agrees to participate, signs the informed consent form, demonstrates good compliance, and agrees to follow-up.

Exclusion criteria

• Patients who meet \*\*any\*\* of the following criteria will be excluded from this study:

• Bilateral breast cancer.
• Metastatic disease at any site.
• Patients with cT > 2 cm or positive lymph nodes \*\*and\*\* carrying pathogenic/likely pathogenic germline BRCA1/2 mutations.
• History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction within the past 6 months, or ventricular arrhythmia.
• History of clinically significant pulmonary disease, including but not limited to interstitial pneumonia, pneumonia, pulmonary fibrosis, and radiation pneumonitis (except for asymptomatic radiation changes not requiring intervention); or suspected such disease based on screening examinations.
• History of other malignancies within the past 5 years, excluding cured carcinoma in situ of the cervix, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.
• Pregnant or lactating women; women of childbearing potential who cannot practice effective contraception.
• Patients concurrently participating in other clinical trials.
• Patients with a history of hypersensitivity or known allergy to any component of the study drugs; or patients with a history of allergy to other monoclonal antibodies.
• Severe or uncontrolled infection.
• Hypertension that cannot be adequately controlled with antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
• History of gastrointestinal bleeding within the past 6 months, or clear tendency for gastrointestinal bleeding, such as esophageal varices at risk of bleeding, locally active ulcerative lesions, or fecal occult blood ≥ (++). Patients with fecal occult blood (+) must undergo gastroscopy for further evaluation.
• Known active HBV or HCV infection (HBV-DNA ≥ 500 IU/mL), or chronic infection with abnormal liver function.
• Urinalysis showing urine protein ≥ ++, or 24-hour urine protein quantification > 1.0 g.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to study enrollment.
• History of drug abuse (psychoactive substances) with inability to abstain, or history of psychiatric disorders.
• Patients deemed unsuitable for participation by the investigator's judgment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07407517 · SCHBCC-N0108

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗