Neoadjuvant Toripalimab and Radiotherapy Treatment in N+ HR+ Breast Cancer

NCT ID: NCT06671262

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-26
• Study Completion Date: 2027-11-01

Brief Summary

The goal of this clinical trial is to compare the efficacy and safety in patients with lymph node-positive HR+/HER2- breast cancer. The main questions it aims to answer are:

• Can the incorporation of intensified radiation to the tumor (tumor boost) enhance the pCR rate on the basis of neoadjuvant immuno-chemotherapy？
• Can it improve the level of residual cancer burden (RCB) and change the tumor immune microenvironment? and How safe will be the combined therapy?

Participants will be randomly assigned to one of three treatment regimens:

1. Preoperative toripalimab combined with SBRT targeting both the primary tumor and axillary lymph nodes, followed by chemotherapy;

2. Preoperative toripalimab combined with SBRT focused solely on the primary tumor, followed by chemotherapy;

3. Preoperative toripalimab combined with chemotherapy alone.

Following the completion of their respective treatment regimens, participants will proceed to undergo surgery. The effectiveness of the treatments will be assessed through pathological evaluations, as well as by measuring levels of residual cancer burden (RCB) and examining changes in the tumor immune microenvironment.

The study aims to evaluate the safety of these combined treatment approaches and to determine if they offer superior efficacy compared to outcomes reported in previous studies.

Detailed Description

Breast cancer is a leading malignancy among women globally, with early diagnosis and treatment being crucial for better outcomes. Over 90% of breast cancer patients are diagnosed at an early stage, and approximately two-thirds have the hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) subtype. Despite this, these patients often exhibit resistance to neoadjuvant chemotherapy, with a pathologic complete response (pCR) rate of only 5-15%, which is significantly lower compared to other subtypes and is associated with poor prognosis. This indicates the necessity for optimizing current treatment strategies.

In recent years, significant advancements have been made in the application of immunotherapy for breast cancer. The studies demonstrated that the addition of immune checkpoint inhibitors to neoadjuvant chemotherapy for patients with high-risk early-stage HR+/HER2- breast cancer significantly improved pCR rates.

Building on these findings, this study proposes a novel strategy of dose-intensified radiation to the tumor (tumor boost) during the neoadjuvant immuno-chemotherapy phase. The advantage of this approach is that it can activate the immune system while the tumor tissue is still intact, providing a rich source of tumor antigens, which aids in enhancing the immune system's recognition and destruction of cancer cells.

Toripalimab is an optimal immunotherapy agent to study, as this agent has recently been approved by the FDA for use in multiple tumor types. It is therefore ready to be tested for efficacy in other disease sites and in combination with other treatments. This study will provide valuable insights into the potential of immunotherapy in combination with radiotherapy to improve outcomes for patients with lymph nodes-positive, high-risk HR+/HER2- breast cancer.

Conditions

Breast Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The control group

Patients in this arm receive only a single injection of toripalimab without any radiotherapy as an initial treatment. After a three-week interval, patients receive the standard neoadjuvant chemotherapy in combination with toripalimab, starting with four cycles of paclitaxel and toripalimab, followed by four cycles of epirubicin and toripalimab.

Group Type: ACTIVE_COMPARATOR

Immuno-chemotherapy

Intervention Type: DRUG

Standard new adjuvant treatment with toripalimab combined with chemotherapy, that is in the first phase consisting of paclitaxel and toripalimab for four cycles, followed by epirubicin, cyclophosphamide, and toripalimab for another four cycles.

The SBRT-combined group 1

Patients enrolled in this treatment arm will undergo SBRT focused on the primary tumor, receiving a total dose of 24Gy divided into three fractions over the course of 3 to 5 working days. Following the radiation therapy, toripalimab will be administered between the second and fifth days post-treatment. After a three-week rest period, patients will commence the standard neoadjuvant chemotherapy regimen combined with toripalimab. This regimen will begin with four cycles of paclitaxel combined with toripalimab and followed by four cycles of epirubicin combined with toripalimab.

Group Type: EXPERIMENTAL

SBRT

Intervention Type: RADIATION

Target the primary tumor region with a single dose of 8Gy, or deliver a dose of 3Gy to the axillary lymph nodes, administered once a day for three consecutive days.

Immuno-chemotherapy

Intervention Type: DRUG

Standard new adjuvant treatment with toripalimab combined with chemotherapy, that is in the first phase consisting of paclitaxel and toripalimab for four cycles, followed by epirubicin, cyclophosphamide, and toripalimab for another four cycles.

The SBRT-combined group 2

In this treatment protocol, patients will receive a total radiation dose of 24Gy in three fractions, specifically targeting the primary tumor. Concurrently, the axillary lymph nodes will be treated with a dose of 9Gy in three fractions. This radiation therapy will be conducted over a period of 3 to 5 working days. Following the radiation therapy, toripalimab will be administered between the second and fifth days after the completion of the radiation treatment. After a three-week interval, patients will proceed with the standard neoadjuvant chemotherapy regimen combined with toripalimab. This regimen includes an initial phase of four cycles of paclitaxel paired with toripalimab, which will be followed by a subsequent phase of four cycles of epirubicin paired with toripalimab.

Group Type: EXPERIMENTAL

SBRT

Intervention Type: RADIATION

Target the primary tumor region with a single dose of 8Gy, or deliver a dose of 3Gy to the axillary lymph nodes, administered once a day for three consecutive days.

Immuno-chemotherapy

Intervention Type: DRUG

Standard new adjuvant treatment with toripalimab combined with chemotherapy, that is in the first phase consisting of paclitaxel and toripalimab for four cycles, followed by epirubicin, cyclophosphamide, and toripalimab for another four cycles.

Interventions

SBRT

Target the primary tumor region with a single dose of 8Gy, or deliver a dose of 3Gy to the axillary lymph nodes, administered once a day for three consecutive days.

Intervention Type: RADIATION

Immuno-chemotherapy

Standard new adjuvant treatment with toripalimab combined with chemotherapy, that is in the first phase consisting of paclitaxel and toripalimab for four cycles, followed by epirubicin, cyclophosphamide, and toripalimab for another four cycles.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• High-risk HR+/HER2-negative breast cancer is defined as ER≥1%, HER2-negative (<2+ Her2 IHC or <2.2 HER2/CEP17 ratio by FISH) and either histologic grade II-III or a high-risk genomic assay score (Oncotype RS>25, high risk Mammaprint, PAM-50, EndoPredict or ProSigna score). primary tumor size ≥1.0 cm in maximum diameter and axillary node-positive breast cancer;
• Stage T1-4N+M0 (i.e., Stage II, III), with confirmed N+ by biopsy, and no signs of distant metastasis;
• The initial PD-L1 expression level conducted on the tumor tissue sample with Combined Positive Score (CPS) or Tumor Proportion Score (TPS)< 10%;
• ECOG score of 0-1;
• Screening laboratory values must meet the following criteria: i. White blood cells (WBCs) ≥ 2000/μL ii. Absolute neutrophil count (ANC) ≥ 1500/μL iii. Platelets ≥ 100 x 103/μL iv. Hemoglobin ≥ 11.0 g/dL v. Serum creatinine ≤ 2 mg/dL (or glomerular filtration rate ≥ 40 ml/min) vi. AST ≤ 2.5 x upper limit of normal (ULN) vii. ALT ≤ 2.5 x ULN viii. Total bilirubin within normal limits (except subjects with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL) ix. INR ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulant(s) x. Negative HIV screening test xi. Negative screening tests for Hepatitis B and Hepatitis C. Patients with positive results that do not indicate true active or chronic infection may enroll after discussion and consensus agreement by the treating physician and principal investigator.

Exclusion Criteria

• Inflammatory breast cancer
• Life-threatening organ dysfunction or complications, active infectious diseases, active hepatitis B, hepatitis C virus infection, autoimmune diseases within two years, undergoing immunosuppressive drug treatment or chronic systemic corticosteroid therapy (dose exceeding 10mg per day of prednisone or equivalent);
• Clinically symptomatic heart disease;
• Previous systemic treatment or radiotherapy for breast cancer;
• Patients with cosmetic breast implants, i.e., having implants under the skin at the time of diagnosis;
• Radiotherapy contraindications: history of radiotherapy;
• Women shall not be breastfeeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jian Huang

Role: CONTACT

drhuangjian@zju.edu.cn

+86-13958123068

Ting Zhang

Role: CONTACT

zezht@zju.edu.cn

+86-571-87783521

Facility Contacts

Ting Zhang, phD

Role: primary

zezht@zju.edu.cn

+86-571-87783521

Other Identifiers

Y2024-0857

Identifier Type: -

Identifier Source: org_study_id