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

Back to results

Primary Purpose

Status

Active

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

epirubicin hydrochloride

Cyclophosphamide

Albumin bound paclitaxel

Toripalimab

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer focused on measuring Programmed Death-1

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Female between 18 to 70 years old.
Patients be diagnosed with primary unilateral invasive breast cancer of cT2-4NanyM0 by histology.
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+.
At least one mensurable objective focus according to RECIST guideline (vision 1.1).
Eastern Cooperative Oncology Group (ECOG) performance status is less than or equal to (</=) 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.
Signed informed consent.
Able to comply with the protocol.

Exclusion Criteria:

Received any previous therapy including cytotoxic chemotherapy, endocrine therapy, biological therapy or radiation therapy for any reason.
Patients with heart disease whose New York Heart Association class (NYHA) is higher or equal to (>/=) Class II.
Severe systemic infection or with other severe disease.
Known hypersensitivity to any of the study drugs or excipients.
Previous non-breast malignancy within 5 years prior to study entry excluding healed cervical carcinoma in situ and non-melanoma skin cancer.
Pregnancy, breast-feeding or child-bearing women who refuse contraception during the trial.
Participants who received any other investigational treatment within 30 days before the first dose of drug investigated.
Patients who are inconformity to participate in this study according to investigators.

Sites / Locations

Shanghai Cancer Center, Fudan University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EC-ABX/PD-1

Arm Description

Patients who are treated with epirubicin hydrochloride andcyclophosphamide followed by nanoparticlealbumin-bound paclitaxel and Toripalimab

Outcomes

Primary Outcome Measures

Pathologic complete response (pCR)

Defined as the absence of any invasive cancer cells in the resected breast specimen and all resected lymph nodes following the completion of neoadjuvant therapy. If there is only carcinoma in situ remains, it can be regarded as pCR.

Secondary Outcome Measures

Change in tumor-infiltrating lymphocytes (TILs)

TILs in tumor samples by biopsy right before the first neoadjuvant therapy (baseline) and by surgery immediately after surgery would be evaluated by HE or immune staining. TILs in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), right before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.

Change in programmed cell death protein 1 (PD1)

PD1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.

Change in programmed cell death ligand 1 (PD-L1)

PD-L1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD-L1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.

Change in androgen receptor (AR)

AR in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. AR in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.

Change in cluster of differentiation 8 (CD8)

CD8 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. CD8 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.

Change in recombinant forkhead box protein C1 (FOXC1)

FOXC1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. FOXC1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.

Objective response rate (ORR)

Defined as the percentage of cases obtaining complete remission and partial response in all evaluable cases.

Rate of breast-conserving surgery

Defined as the percentage of patients who have breast-conserving surgery in all evaluable patients.

Full Information

NCT ID

NCT04418154

First Posted

May 25, 2020

Last Updated

July 4, 2023

Sponsor

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT04418154

Brief Title

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

Official Title

Dose-dense Epirubicin Hydrochloride With Cyclophosphamide Followed by Nanoparticlealbumin-bound Paclitaxel With PD-1 Regimen in Neoadjuvant Therapy for Patients With Triple-negative Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 9, 2020 (Actual)

Primary Completion Date

September 1, 2022 (Actual)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Triple Negative Breast Cancer

Keywords

Programmed Death-1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

EC-ABX/PD-1

Arm Type

Experimental

Arm Description

Patients who are treated with epirubicin hydrochloride andcyclophosphamide followed by nanoparticlealbumin-bound paclitaxel and Toripalimab

Intervention Type

Drug

Intervention Name(s)

epirubicin hydrochloride

Intervention Description

Take epirubicin hydrochloride (90mg/m2, d1) every 14 days as one cycle for 4 cycles with cyclophosphamide, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

Take cyclophosphamide (600mg/m2, d1) every 14 days as one cycle for 4 cycles with epirubicin hydrochloride, followed by nanoparticlealbumin-bound paclitaxel and Toripalimab.

Intervention Type

Drug

Intervention Name(s)

Albumin bound paclitaxel

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Toripalimab

Intervention Description

Take Toripalimab (240mg, d1) every 3 weeks as one cycle for 4 cycles with nanoparticlealbumin-bound paclitaxel, following epirubicin hydrochloride and cyclophosphamide.

Primary Outcome Measure Information:

Title

Pathologic complete response (pCR)

Description

Defined as the absence of any invasive cancer cells in the resected breast specimen and all resected lymph nodes following the completion of neoadjuvant therapy. If there is only carcinoma in situ remains, it can be regarded as pCR.

Time Frame

Immediately after the surgery

Secondary Outcome Measure Information:

Title

Change in tumor-infiltrating lymphocytes (TILs)

Description

TILs in tumor samples by biopsy right before the first neoadjuvant therapy (baseline) and by surgery immediately after surgery would be evaluated by HE or immune staining. TILs in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), right before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.

Time Frame

before the first neoadjuvant chemotherapy (baseline), at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery

Title

Change in programmed cell death protein 1 (PD1)

Description

PD1 in tumor samples by biopsy at baseline and by surgery immediately after surgery would be evaluated by HE or immune staining. PD1 in blood at baseline, at the end of Cycle 2, Cycle 4, Cycle 6 and Cycle 8 of neoadjuvant therapy (each cycle is 28 days), before and immediately after the surgery would also be obtained to evaluate its trends for the treatment.

Time Frame