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

NCT06671262 | Recruiting Phase 2 DMC

• 1 other identifier: Y2024-0857
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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:
• Preoperative toripalimab combined with SBRT targeting both the primary tumor and axillary lymph nodes, followed by chemotherapy;
• Preoperative toripalimab combined with SBRT focused solely on the primary tumor, followed by chemotherapy;
• Preoperative toripalimab combined with chemotherapy alone.

Conditions

Breast Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• pCR rate

  Pathological Complete Response (pCR) is characterized by the absence of any invasive residual primary tumor in both the breast and lymph nodes. The primary objective of this study is to compare the pCR rates between two treatment approaches: neoadjuvant toripalimab combined with SBRT followed by immuno-chemotherapy, and neoadjuvant toripalimab combined with chemotherapy.

  At the end of immuno-chemotherapy up to 4-6 months

Secondary Outcomes (3)

• RCB level

  breast surgery up to 4-6 months after trial initiation

• TILs

  Pre-treatment, post-initial dose of Toripalimab with or without radiation up to 4 weeks, and at surgical resection up to 4-6 months.

• SBRT-related Adverse Events

  at least once a week within 2-4 weeks after the start of radiotherapy.

Study Arms (3)

The control group

ACTIVE COMPARATOR

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.

Drug: Immuno-chemotherapy

The SBRT-combined group 1

EXPERIMENTAL

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.

Radiation: SBRT; Drug: Immuno-chemotherapy

The SBRT-combined group 2

EXPERIMENTAL

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.

Radiation: SBRT; Drug: Immuno-chemotherapy

Interventions

SBRT 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.

The SBRT-combined group 1; The SBRT-combined group 2

Immuno-chemotherapy 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; The SBRT-combined group 2; The control group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

RECRUITING

Central Study Contacts

Jian Huang

CONTACT

+86-13958123068; drhuangjian@zju.edu.cn

Ting Zhang

CONTACT

+86-571-87783521; zezht@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: November 4, 2024
• Study Start: December 26, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: February 11, 2025

Record last verified: 2024-12

Locations

CN (1)