Clinical trial NCT05302336: AC vs TC in Patients With HR-positive, HER2-negative Early Breast Cancer
Official title: A Randomized Controlled Study of AC (Doxorubicin Hydrochloride Liposome/Cyclophosphamide) vs TC (Docetaxel/Cyclophosphamide) Regimens for Postoperative Adjuvant Chemotherapy in Patients With HR-positive, HER2-negative Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Breast Cancer
Chemotherapeutic Toxicity
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2022-03-31
Enrollment: 402
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Anthracycline-paclitaxel sequential combination therapy is the standard regimen for perioperative chemotherapy in breast cancer. The strategy of perioperative chemotherapy is based on breast cancer subtype, i.e. choice of chemotherapy regimen and hormone receptor (HR) \[estrogen receptor and/or progesterone receptor\], human epidermal growth factor receptor 2 (HER2) related. Although HR-positive breast cancer has a better prognosis than other subtypes, standard chemotherapy for HR-positive breast cancer has not been established. The American Oncology Research Trial 9735 demonstrated that docetaxel + cyclophosphamide (TC) produced better results than doxorubicin + cyclophosphamide (AC) in adjuvant breast cancer treatment. However, the enrolled subjects of the 9735 trial did not strictly limit the tumor size, and the tumor size of some patients was greater than 5 cm; the hormone status of the patients was not limited, about 1/3 of the patients were ER negative, and the HER-2 status of the patients was not limited; 9735 Half of the trial's enrolled population had axillary lymph node metastases. From a large number of clinical studies, it has been found that the patient's tumor size, ER negative, HER-2 positive, lymph node metastasis and other factors are risk factors for breast cancer recurrence and metastasis after surgery. Therefore, for HR-positive, HER-2-negative early breast cancer patients, whether the TC regimen is superior to the AC regimen remains uncertain. The current CSCO breast cancer treatment still recommends the AC regimen as one of the options for adjuvant breast cancer treatment. Other studies have shown a benefit of anthracyclines in high-risk HR-positive disease, and TC is a suitable option for lower risk. The TC regimen had a higher incidence of myelosuppression and allergy than the AC regimen.

Detailed description: At present, the liposomal doxorubicin developed on the basis of doxorubicin has been used for the first-line treatment of advanced breast cancer, and both NCCN and CSCO guidelines have related recommendations. However, the application of liposomal doxorubicin in adjuvant therapy of breast cancer still lacks sufficient evidence-based medicine. The current research shows that doxorubicin under the encapsulation of liposomes prolongs the half-life of the drug, reduces the cardiotoxicity, and the drug is continuously enriched in the tumor tissue to improve the anti-tumor activity. In addition, liposomal doxorubicin has the advantage of less hair loss during chemotherapy, which meets the needs of some clinical patients for hair protection. There is still a lack of clinical studies on the use of AC (liposomal doxorubicin/cyclophosphamide) with other early breast cancer adjuvant chemotherapy regimens. This study aimed to evaluate the efficacy and safety of AC (liposomal doxorubicin + cyclophosphamide) and TC (docetaxel + cyclophosphamide) regimens as adjuvant therapy for HR+ HER2- early breast cancer.

Eligibility criteria: Inclusion Criteria:

1. Age: 18\~70 years old, female;
2. Patients with primary breast cancer diagnosed by histopathology and clinical stage of T1b-2 N0;
3. The expression of HER-2 is negative by immunohistochemistry (IHC). If the expression of HER-2 is 2+, in situ hybridization is required to confirm that the HER-2 gene is not amplified; HR+.
4. ECOG physical fitness score 0-1 points;
5. LVEF≥55%;
6. Bone marrow function: neutrophils≥1.5×109/L, platelets≥100×109/L, hemoglobin≥90g/L;
7. Liver and kidney function: serum creatinine ≤1.5 times the upper limit of normal; AST and ALT ≤2.5 times the upper limit of normal; total bilirubin ≤1.5 times the upper limit of normal, or ≤2.5 times the upper limit of normal when the patient has Gilbert's syndrome ;
8. The patient has good compliance with the planned treatment, can understand the research process of this study and sign the written informed consent.

Exclusion Criteria:

1. Received cytotoxic chemotherapy, endocrine therapy, biological therapy or radiation therapy for any reason;
2. New York Heart Association (NYHA) score identifies patients with heart disease of grade II or above (including grade II);
3. Patients with severe systemic infection or other serious diseases;
4. Patients who are known to be allergic or intolerant to chemotherapy drugs or their excipients;
5. Other malignant tumors have occurred in the past 5 years, except for skin cancer of cured cervical carcinoma in situ and non-melanoma;
6. Patients of childbearing age who are pregnant or breastfeeding and who refuse to take appropriate contraceptive measures during this trial;
7. Participated in other experimental studies within 30 days before the administration of the first dose of the investigational drug;
8. Patients judged by the investigator to be inappropriate to participate in this study.

Primary outcomes:
measure: disease-free survival
timeFrame: 5 years
Secondary outcomes:
measure: side effect
timeFrame: 1 year
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: Second Affiliated Hospital, School of Medicine, Zhejiang University, China
state: Zhejing
Study officials:
References: