Health Trials

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

ConditionBreast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18-75
SponsorXijing Hospital

About this trial

The goal of this clinical trial is to evaluate the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) followed by nab-paclitaxel combined with toripalimab in patients with previously untreated HR+/HER2-negative breast cancer. Eligible patients include those with stage IIB-IIIC disease (cT3N0, cT2-4N1-3 or cT1N2-3) or stage IIA disease (cT2N0 or cT1N1) with at least two of the following high-risk factors: histologic grade 3, Ki-67 ≥50% or premenopausal with age \<50 years. A total of 27 enrolled patients will be assigned to receive the combination therapy. The primary question it aims to answer is whether this combination of radiotherapy, de-escalated chemotherapy, and immunotherapy can improve the total pathologic complete response (tpCR) rate (defined as ypT0/Tis ypN0).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Female patients aged ≥18 and ≤75 years at the time of signing informed consent.

ECOG PS status of 0-1.

Grade 2 or 3 (confirmed by central laboratory);

ER-positive (>1% staining) and/or PR-positive (>1% staining) by IHC;

Disqualifiers

Inflammatory Breast Cancer.

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);

Trial design

Design model

Single group

Treatments tested in this trial

  • 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.

  • 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)

  • 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).

  • Surgery

    Procedure/Surgery

    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.

  • 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)

  • 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.

  • 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 groups

27 Participants
are divided into 1 treatment group
Group A: TreatmentExperimental treatment 7 interventions

Trial outcomes

Primary outcomes

1

Total pathologic complete response (tpCR) rate according to RCB system

tpCR is defined as the absence of invasive carcinoma 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

Time frame
At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.

Secondary outcomes

1

RCB 0/I rate

The RCB 0/I rate is defined as the percentage of patients achieving either pathological complete response (RCB-0) or minimal residual disease (RCB-I), corresponding to near-pCR status

Time frame
At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
2

Breast pathologic complete response (bpCR) rate

bpCR is defined as the absence of residual invasive carcinoma in the breast primary lesion (ypT0/Tis; ductal carcinoma in situ may be present), regardless of regional lymph node status, assessed by hematoxylin and eosin (H\&E) staining after neoadjuvant therapy.

Time frame
At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
3

Axillary pathologic complete response (apCR) rate

apCR is defined as negative pathologic status of axillary lymph nodes (ypN0) after neoadjuvant therapy, assessed by H\&E staining.

Time frame
At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
4

Objective response rate (ORR)

ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) per RECIST version 1.1, as assessed by the investigator.

Time frame
From start of neoadjuvant therapy until definitive surgery, assessed every 2 cycles (each cycle is 21 days) during neoadjuvant treatment.

Other outcomes

1

Correlation of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) with efficacy

To evaluate the association between baseline PD-L1 expression status (by IHC) and TILs density (by HE staining and IHC) in pre-treatment tumor tissue and pathologic response (tpCR, RCB 0/I, bpCR, apCR)

Time frame
PD-L1 and TILs will be evaluated at baseline (pre-treatment), and pathologic response will be assessed at definitive surgery (approximately 4 months after initiation of neoadjuvant therapy).
2

Effect of treatment on the immune microenvironment of HR+/HER2- breast cancer

To explore the percentage change (unit of measure: percentage of positive cells and relative expression change) in tumor immune microenvironment markers (e.g., immune cell infiltration, PD-L1 expression) induced by neoadjuvant treatment, assessed by IHC in paired pre- and post-treatment tumor tissue samples.

Time frame
Baseline (pre-treatment) and perioperative (at definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab, each cycle is 21 days, approximately 4 months).

Sponsors and contacts

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Xijing Hospital

Lead sponsor

Source ClinicalTrials.gov
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