Neoadjuvant Dose-dense EC Followed by ABX With PD-1 for Triple Negative Breast Cancer Patients

Triple Negative Breast Cancer Clinical Trial

— NeoTENNIS  

Official title:

Neoadjuvant Anthracycline Followed by Toripalimab Combined With Nab-paclitaxel in Patients With Early Triple-negative Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04418154
• Other study ID #: SCHBCC-N027
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 9, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: December 31, 2025
• Est. primary completion date: September 28, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• epirubicin hydrochloride
Take epirubicin hydrochloride (90mg/m2, d1) every 14 days as one cycle for 4 cycles with cyclophosphamide, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.
• Cyclophosphamide
Take cyclophosphamide (600mg/m2, d1) every 14 days as one cycle for 4 cycles with epirubicin hydrochloride, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.
• Albumin bound paclitaxel
Take nanoparticlealbumin-bound paclitaxel (125mg/m2, d1) per week for 3 weeks as one cycle for 4 cycles with Toripalimab, following epirubicin hydrochloride and cyclophosphamide.
• Toripalimab
Take Toripalimab (240mg, d1) every 3 weeks as one cycle for 4 cycles with nanoparticlealbumin-bound paclitaxel, following epirubicin hydrochloride and cyclophosphamide.

Locations

Country	Name	City	State
China	Shanghai Cancer Center, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Pathologic complete response (tpCR)	Defined as no residual invasive cancer cells are found in the pathological examination of breast and axillary lymph node; if only residual in situ cancer cells are present in the surgical specimens, it can also be considered as achieving a pathological complete response.	Immediately after the surgery
Secondary	Breast pathologic complete response (bpCR: ypT0/is) rate	Defined as the absence of invasive cancer cells in breast.	Immediately after the surgery
Secondary	Objective response rate (ORR)	Defined as the proportion of patients with a complete or partial response by MRI.	Immediately after the surgery
Secondary	Breast conservative surgery rate	Defined as the percentage of patients who undergo breast-conserving surgery after neoadjuvant therapy, out of the total number of evaluable cases.	Immediately after the surgery
Secondary	Event-free survival (EFS)	Defined as the time from the date of the first study dose to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.	Approximately 3 years
Secondary	Adverse events (AEs)	Refer to any untoward medical occurrence in a study subject administered an investigational product which does not necessarily have a causal relationship with the treatment. AE is assessed according to the NCI-CTCAE 5.0.	During this period between the start of randomization and the last visit, approximately 3 years
Secondary	Change in immune-related tissue biomarkers	The proportion of Tumor-infiltrating lymphocytes (TILs) is evaluated through HE staining. Immunohistochemical staining of PD-1, PD-L1, AR, CD8, and FOXC1) is performed. TILs, PD1, PD-L1, AR, CD8, and FOXC1 in tumor samples by biopsy at baseline, at the end of Cycle 2 and by surgery immediately after surgery would be evaluated by HE or immune staining.	At baseline, at the end of first 2 cycles (each cycle is 14 days) and immediately after the surgery