Neoadjuvant SBRT Followed by Nab-Paclitaxel Combined With Toripalimab in HR+/HER2- Breast Cancer

NCT06914440 | Recruiting Phase 2 DMC

• 1 other identifier: XJ-ViBranT-B-001
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of neoadjuvant radiotherapy followed by chemotherapy combined with immunotherapy in patients with previously untreated stage IIB-IIIC (cT3N0 or cT2-4N1-3) HR-positive and HER2-negative breast cancer. 27 enrolled patients will be assigned to receive stereotactic body radiotherapy followed by Nab-Paclitaxel combined with Toripalimab. The main question it aims th answer is that whether the combination therapy of radiotherapy, de-escalated chemotherapy, and immunotherapy could improve the pCR rate of HR-positive and HER2-negative breast cancer.

Conditions

Breast Cancer

Keywords

Breast Cancer; Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR) rate according to RCB system

  pCR is defined as the absence of invasive cancer in the breast primary lesion and negative regional lymph nodes (ypT0/Tis ypN0) by hematoxylin-eosin staining after completion of the neoadjuvant treatment. RCB system will be used for the pathological evaluation after neoadjuvant therapy

  Up to 12 months

Secondary Outcomes (2)

• RCB 0/I rate

  Up to 12 months

• DFS and iDFS

  1 year, 2 year, 3 year and 5 year

Study Arms (1)

Treatment

EXPERIMENTAL

During the neoadjuvant treatment period, participants will undergo stereotactic radiotherapy and subsequently receive chemotherapy combined with immunotherapy.

Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Toripalimab; Drug: Neoadjuvant Chemotherapy; Procedure: Surgery; Drug: Adjuvant Chemotherapy; Radiation: Adjuvant Radiotherapy; Drug: Endocrine therapy

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

The prescribed dose of radiation is 24 Gy delivered in 3 fractions (8 Gy/fraction) using SBRT technique. Subjects received SBRT for the primary breast cancer lesion at 8Gy/Fraction each time for 3 consecutive days, 1 week before the start of systemic therapy. The first day of radiation is C1D1.

Treatment

Toripalimab DRUG

Toripalimab will be administered at a fixed dose of 240 mg via intravenous infusion every 3 weeks (q3w). The first dose is given on Cycle 2 Day 1 (C2D1), followed by dosing on the first day of each subsequent cycle for a total of 4 cycles. (Toripalimab×4 240mg D1 q3w)

Treatment

Neoadjuvant Chemotherapy DRUG

Combined with Toripalimab, Nab-paclitaxel will be dosed at 125 mg/m² based on body surface area, administered by intravenous infusion weekly (Days 1, 8, 15 of each 21-day cycle) for 4 cycles.(T×4, Nab-Paclitaxel 125mg/m2，D1、D8、D15 q3w).

Treatment

Surgery PROCEDURE

Surgery will be performed 2-6 weeks after completion of neoadjuvant therapy. The surgical approach will be determined by the investigator based on disease status and patient preference.

Treatment

Adjuvant Chemotherapy DRUG

The anthracycline may be either Epirubicin (body surface area-adjusted 50 mg/m²) or Liposomal Doxorubicin (body surface area-adjusted 30 mg/m²) combined with Cyclophosphamide (body surface area-adjusted 600 mg/m²). Both drugs were administered intravenously every 3 weeks, and then the first day of each course was administered for 4 cycles. (EC×4, Epirubicin 50 mg/m² or Liposomal Doxorubicin 30 mg/m², comined with Cyclophosphamide 600 mg/m², D1, q3w)

Treatment

Adjuvant Radiotherapy RADIATION

Conventional radiotherapy will be delivered to the breast/chest wall and regional lymph nodes (investigator-selected technique), with explicit prohibition of tumor bed boost irradiation.

Treatment

Endocrine therapy DRUG

Investigator-selected adjuvant endocrine therapy will be deterimend according to applicable guidelines, considering menopausal status, recurrence risk, treatment history, comorbidities as well as patient preference.

Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients aged ≥18 and ≤75 years at the time of signing informed consent.
• ECOG PS status of 0-1.
• Breast cancer assessed as non-metastatic (M0), meeting all of the following:
• Clinical stage: Stage IIB, IIIA, IIIB, or IIIC
• Required imaging assessments (within 28 days): Abdominal CT, ECT Bone scan, Chest CT and Brain MRI
• Histologically or pathologically confirmed invasive carcinoma of no special type, with all of the following:
• Grade 2 or 3 (confirmed by central laboratory);
• ER-positive (\>1% staining) and/or PR-positive (\>1% staining) by IHC;
• HER2-negative (IHC 0/1+ or HER2/neu FISH ratio ≤1.8);
• Ki-67 ≥15%.
• Patient deemed eligible for radiotherapy after MDT evaluation.
• No prior antitumor therapy within 1 month before enrollment.
• Organ Function Requirements (within 7 days prior to enrollment):
• Complete blood count (no transfusion or hematopoietic growth factors within 7 days): ANC ≥1.5×10⁹/L; ALC ≥0.5×10⁹/L; Platelets ≥100×10⁹/L; Hemoglobin ≥90 g/L; WBC ≥3.0×10⁹/L and ≤15×10⁹/L;
• Blood biochemistry (no transfusion/albumin within 7 days): ALT/AST ≤2.5×ULN; ALP ≤2.5×ULN；BUN/Cr ≤1.5×ULN; Cr≥60 mL/min (Cockcroft-Gault formula);

You may not qualify if:

• Inflammatory Breast Cancer.
• Comorbidities/Medical History:
• Autoimmune disease: patients with any known or suspected autoimmune disease, except: hypothyroidism due to autoimmune thyroiditis managed with hormone replacement therapy only, stable type-1 diabetes with well-controlled blood glucose.
• Cardiovascular Diseases: poorly controlled hypertension despite medication (SBP \>140 mmHg or DBP\>90 mmHg). And with the history (within 6 months prior to enrollment) of myocardial infarction, severe/unstable angina, NYHA Class ≥2 heart failure, clinically significant arrhythmias as well as symptomatic congestive heart failure.
• Interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases (e.g., diabetes, pulmonary fibrosis, acute pneumonia);
• Vaccination: receipt of live attenuated vaccines within 28 days prior to enrollment or planned during the study;
• Infections: HIV/AIDS, active hepatitis(HBV-DNA ≥500 IU/mL; HCV-RNA above detection limit), or co-infection with HBV and HCV, severe infections within 4 weeks prior to enrollment (e.g., bacteremia, severe pneumonia requiring hospitalization), active infection requiring systemic antibiotics (CTCAE≥Grade 2) within 2 weeks prior to treatment, active tuberculosis within 1 year prior to enrollment;
• Unexplained fever \>38.5°C during screening (unless deemed tumor-related by the investigator);
• Malignancy History: other malignancies diagnosed within 5 years prior to enrollment (except adequately treated basal cell carcinoma, squamous cell skin cancer, or cervical carcinoma in situ);
• Surgery:Major surgery within 28 days prior to enrollment (diagnostic biopsies or PICC line placement are allowed);
• Transplant: Prior or planned allogeneic bone marrow or solid organ transplant;
• Neurological: peripheral neuropathy ≥Grade 2;
• Gastrointestinal: clinically significant bowel obstruction;
• Thrombotic Events: arterial/venous thrombosis within 6 months prior to enrollment (e.g., stroke, transient ischemic attack, DVT, pulmonary embolism);
• Bleeding Risk: hemoptysis (≥2.5 mL/day) within 2 months prior to enrollment, clinically significant bleeding within 3 months prior to enrollment (e.g. gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood≥++), and the known bleeding/thrombotic disorders (e.g., hemophilia, coagulopathy, thrombocytopenia, hypersplenism);

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (2)

Xijing Hospital Affiliated to Air Force Military Medical University

Xi'an, Shannxi Province, 710032, China

RECRUITING

Xijing Hospital Affiliated to Air Force Military Medical University

Xi'an, Shannxi, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiosurgery; toripalimab; Neoadjuvant Therapy; Surgical Procedures, Operative; Chemotherapy, Adjuvant; Radiotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Investigative Techniques; Combined Modality Therapy; Drug Therapy

Central Study Contacts

JIAJUN DING

CONTACT

15121089323; yuki_ding1996@163.com

Study Design

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

Study Record Dates

• First Submitted: March 30, 2025
• First Posted: April 6, 2025
• Study Start: June 5, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 1, 2030
• Last Updated: July 15, 2025

Record last verified: 2025-03

Locations

CN (2)