Clinical trial NCT04418154: Neoadjuvant Dose-dense EC Followed by ABX With PD-1 for Triple Negative Breast Cancer Patients
Official title: Neoadjuvant Anthracycline Followed by Toripalimab Combined With Nab-paclitaxel in Patients With Early Triple-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
Keywords: Programmed Death-1
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-06-05
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the efficacy and safety for dose-dense epirubicin hydrochloride with cyclophosphamide followed by nanoparticlealbumin-bound paclitaxel with PD-1 in neoadjuvant therapy for patients with triple-negative breast cancer, and to explore the predictive value of biological markers for the treatment.

Detailed description: This study is an open single arm study, which would undergo optimal two stage designs. 60 patients who are diagnosed with triple-negative breast cancer would have dose-dense epirubicin hydrochloride with cyclophosphamide followed by nanoparticlealbumin-bound paclitaxel with PD-1 regimen for neoadjuvant therapy if they meet the eligibility criteria. The regimen is as follows: epirubicin hydrochloride (90mg/m2, d1) plus cyclophosphamide (600mg/m2, d1) every 14 days as one cycle for 4 cycles, followed by nanoparticlealbumin-bound paclitaxel (125mg/m2, d1) per week for 3 weeks as one cycle for 4 cycles, and Toripalimab (240mg, d1) every 3 weeks as one cycle for 4 cycles. pathological complete response would be the primary endpoint. The change of biological markers and safety of the regimen would also be evaluated.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 70 years old, female.
* Patients with histologically confirmed unilateral primary invasive breast cancer who meet the criteria of cT2-4NanyM0.
* Patients with ER negative and PR negative by immunohistochemistry (IHC), and HER-2 negative disease. HER2-negative disease was defined as follows: disease whose HER-2 is 1+ or negative by IHC, or fluorescence in situ hybridization (FISH) is negative if IHC is 2+.
* According to the RECIST 1.1 criteria, there is at least one measurable objective lesion.
* Eastern Cooperative Oncology Group (ECOG) performance score 0-1.
* Baseline left ventricular ejection fraction (LVEF) is greater than or equal to (\>/=) 55%.
* Bone marrow function is required as follows: neutrophils are more than or equal to (\>/=) 1.5×109/L, platelets more than or equal to (\>/=) 100×109/L, and hemoglobin more than or equal to (\>/=) 90g/L.
* Hepatic and renal function are required as follows: serum creatinine is less than or equal to (\</=) 1.5 times of upper limits of normal (ULN), aspartate transaminase (AST) and alanine aminotransferase (ALT) less than or equal to (\</=) 2.5 times of ULN, and total bilirubin less than or equal to (\</=) 1.5 times of ULN or \</= 2.5 times of ULN if patient is with Gilbert's syndrome.
* With good compliance with the planned treatment, are able to understand the follow-up procedures of this study and sigh the informed consent form.

Signed informed consent.

Exclusion Criteria:

* Received radiotherapy, chemotherapy, surgery or other targeted and immunotherapy for triple-negative breast cancer before enrollment.
* With heart disease classified as New York Heart Association class (NYHA) grade II or above (including grade II) are identified by the investigator.
* With severe systemic infection or those with other serious illnesses.
* Known to be allergic or intolerant to chemotherapy drugs or their excipients.
* With a history of autoimmune diseases or those using glucocorticoids or immunosuppressive drugs.
* With known active stage of HBV or HCV infection or hepatitis B DNA ≥500, or patients with chronic abnormal liver function.
* With a history of abnormal thyroid function.
* With grade ≥ 2 peripheral neuropathy.
* With a clear history of neurological or mental disorders, including epilepsy or dement.
* Previous non-breast malignancy within 5 years prior to study entry excluding healed cervical carcinoma in situ and non-melanoma skin cancer.
* History of other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ and non-melanoma skin cancer.
* Pregnancy or lactation, and patients of childbearing potential who refuse to use adequate contraception during the course of this study.
* Prior participation in other studies within 30 days prior to the administration of the first dose of the investigational drug.
* Patients who are deemed to be unsuitable for this study by investigators.

Primary outcomes:
measure: Total Pathologic complete response (tpCR)
timeFrame: Immediately after the surgery
Secondary outcomes:
measure: Breast pathologic complete response (bpCR: ypT0/is) rate
timeFrame: Immediately after the surgery
measure: Objective response rate (ORR)
timeFrame: Immediately after the surgery
measure: Breast conservative surgery rate
timeFrame: Immediately after the surgery
measure: Event-free survival (EFS)
timeFrame: Approximately 3 years
measure: Adverse events (AEs)
timeFrame: During this period between the start of randomization and the last visit, approximately 3 years
measure: Change in immune-related tissue biomarkers
timeFrame: At baseline, at the end of first 2 cycles (each cycle is 14 days) and immediately after the surgery
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Cancer Center, Fudan University
state: Shanghai
Study officials:
References: