Ignite Creation Date:
2026-03-26 @ 3:14 PM
Ignite Modification Date:
2026-03-30 @ 9:51 PM
Study NCT ID:
NCT07457359
Status:
RECRUITING
Last Update Posted:
2026-03-09
First Post:
2026-03-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Neoadjuvant Toripalimab Plus SBRT for Chemo-Resistant Triple-Negative Breast Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D064726', 'term': 'Triple Negative Breast Neoplasms'}], 'ancestors': [{'id': 'D001943', 'term': 'Breast Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000656314', 'term': 'toripalimab'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 18}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2026-01-04', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2029-01-04', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-04', 'studyFirstSubmitDate': '2026-03-04', 'studyFirstSubmitQcDate': '2026-03-04', 'lastUpdatePostDateStruct': {'date': '2026-03-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-01-04', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'pCR rate', 'timeFrame': 'At definitive surgery, 3-5 weeks after completion of cycle 4 (week 15 from study entry)', 'description': 'Pathological complete response (pCR), percentage of patients with no invasive residual tumor in breast and lymph nodes (ypT0/is ypN0) at surgery.'}], 'secondaryOutcomes': [{'measure': 'ORR Rate', 'timeFrame': 'After cycle 4, within 2 weeks before surgery (week 13).', 'description': 'Proportion of patients achieving complete or partial tumor shrinkage by RECIST 1.1 on MRI.'}, {'measure': 'Acute and late toxicities', 'timeFrame': 'From first SBRT fraction to 30 days post-SBRT (week 5); From first toripalimab dose to 90 days after last dose (week 28)', 'description': 'Acute Radiation Skin Reaction;Immune-Related Adverse Events (irAEs)'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['chemo-resistance', 'neoadjuvant SBRT'], 'conditions': ['TNBC, Triple Negative Breast Cancer']}, 'descriptionModule': {'briefSummary': 'The goal of this clinical trial is to test whether a "rescue" strategy can turn chemotherapy-resistant triple-negative breast cancer (TNBC) into a curable state. Patients whose tumors fail to shrink after 2 cycles of standard neoadjuvant chemotherapy will receive a short, high-precision course of stereotactic body radiotherapy (SBRT, 24 Gy in 3 daily fractions) to the breast primary tumor, followed by 4 cycles of toripalimab (an anti-PD-1 antibody) combined with albumin-bound paclitaxel plus carboplatin. The main questions are:\n\nCan this SBRT-immuno-chemo triplet raise the pathologic complete response (pCR; no invasive cancer in breast or nodes at surgery)? Can it produce an objective radiologic response (ORR) in at least half of the patients, allowing more breast-conserving operations and fewer mastectomies? Secondary objectives include safety, changes in tumor-infiltrating lymphocytes (TILs), event-free survival, and exploratory biomarkers (whole-exome and RNA-seq, PBMC immunoprofiling) to discover signatures of benefit. Participants will undergo image-guided core biopsies before and after SBRT, provide serial blood samples, and have definitive surgery 3-5 weeks after the last cycle.', 'detailedDescription': 'This is a single-arm, single-center, phase II exploratory trial designed for chemotherapy-refractory, early-stage triple-negative breast cancer (Stage II-III). After two cycles of standard neoadjuvant chemotherapy (taxane ± anthracycline ± platinum), patients with stable disease (SD) or progressive disease (PD) by RECIST 1.1 are eligible.\n\nIntervention sequence:\n\nDay 1-3: SBRT 8 Gy × 3 fractions to the intact breast primary (total 24 Gy) under daily image guidance.\n\nDay 4: first dose of toripalimab 240 mg IV. Day 21 (±3 d): start cycle 2 of toripalimab 240 mg d1 + albumin-bound paclitaxel 125 mg/m² d1,8 + carboplatin AUC 6 d1, q21 d × 4 cycles (immunotherapy always given first on day 1).\n\nSurgery: within 3-5 weeks after cycle 4; sentinel-node or axillary dissection per institutional standard. Adjuvant radiation (standard whole-breast/chest-wall plus nodal fields) is delivered post-operatively, but no further boost to the primary tumour bed is required.\n\nEndpoints Primary: pCR rate (ypT0/is ypN0) in the intent-to-treat population. Secondary: ORR by RECIST 1.1 after 4 cycles, change in TILs (H\\&E-based, % stromal area), safety (CTCAE v5.0), event-free survival, overall survival, and rate of breast-conserving surgery. Exploratory: genomic scars, PD-L1, interferon signature, TCR clonality, ctDNA dynamics.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'genderBased': True, 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Female, age 18-75 years, newly diagnosed invasive breast cancer.\n* Histologically confirmed triple-negative phenotype: ER \\< 1 %, PR \\< 1 % by IHC, HER2 negative (IHC 0/1+ or IHC 2+ with ISH negative).\n* Clinical stage II-III (T2-4 or N1-3, M0).\n* Completed 2 cycles of standard neoadjuvant chemotherapy (taxane ± anthracycline ± platinum) and assessed as non-responder: stable disease (SD) or progressive disease (PD) by RECIST 1.1.\n* ECOG performance status 0 or 1.\n* Radiation oncologist confirms suitability for SBRT and subsequent standard post-operative radiotherapy.\n* Adequate organ function within 14 days before enrollment: WBC ≥ 2 000/µL, ANC ≥ 1 500/µL, platelets ≥ 100 000/µL, Hb ≥ 9 g/dL; Serum creatinine ≤ 2 mg/dL or GFR ≥ 40 mL/min; AST/ALT ≤ 2.5 × ULN, total bilirubin ≤ ULN (≤ 3 mg/dL if Gilbert syndrome); INR ≤ 1.5 (on anticoagulation allowed if therapeutic range)\n* Negative HIV, HBV surface antigen, and HCV antibody (or HBV DNA / HCV RNA negative if false-positive).\n\nExclusion Criteria:\n\n* Inflammatory breast cancer.\n* Any other malignancy requiring treatment within the past 3 years (except adequately treated basal-cell skin carcinoma or cervical CIS).\n* Active autoimmune disease, immunodeficiency, or systemic steroids \\> 10 mg/day prednisone equivalent within 2 years.\n* Clinically significant cardiovascular disease (unstable angina, NYHA III/IV heart failure, recent MI).\n* Prior radiotherapy to the breast or chest wall.\n* Active infection requiring systemic therapy.\n* Known intolerance or hypersensitivity to toripalimab, paclitaxel, or carboplatin.\n* Pregnant or lactating women.'}, 'identificationModule': {'nctId': 'NCT07457359', 'acronym': 'NEOTRIO-2', 'briefTitle': 'Neoadjuvant Toripalimab Plus SBRT for Chemo-Resistant Triple-Negative Breast Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Second Affiliated Hospital, School of Medicine, Zhejiang University'}, 'officialTitle': 'Neoadjuvant Toripalimab Combined With Preoperative Radiotherapy for Initial Chemotherapy-Nonresponding Triple-Negative Breast Cancer Patients (NEOTRIO-2)', 'orgStudyIdInfo': {'id': 'Y2025-1398'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'SBRT-Toripalimab-Chemo Rescue', 'description': 'All enrolled participants receive the same regimen:\n\n1. Stereotactic Body Radiation Therapy (SBRT): started within 1 week after confirmation of chemotherapy resistance.\n2. Toripalimab (anti-PD-1 antibody): cycle 1 starts the day after SBRT ends.\n3. Chemotherapy switch: every 21 days for 4 cycles.', 'interventionNames': ['Radiation: SBRT', 'Drug: Toripalimab (anti-PD-1 antibody)', 'Drug: Chemotherapy switch']}], 'interventions': [{'name': 'SBRT', 'type': 'RADIATION', 'description': '24 Gy in 3 daily fractions (8 Gy each) to the breast primary tumor, started within 1 week after confirmation of chemotherapy resistance.', 'armGroupLabels': ['SBRT-Toripalimab-Chemo Rescue']}, {'name': 'Toripalimab (anti-PD-1 antibody)', 'type': 'DRUG', 'description': '240 mg intravenous infusion every 21 days for 4 cycles', 'armGroupLabels': ['SBRT-Toripalimab-Chemo Rescue']}, {'name': 'Chemotherapy switch', 'type': 'DRUG', 'description': 'Albumin-bound paclitaxel 125 mg/m² (days 1 \\& 8) plus carboplatin AUC 6 (day 1)', 'armGroupLabels': ['SBRT-Toripalimab-Chemo Rescue']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Hangzhou', 'status': 'RECRUITING', 'country': 'China', 'facility': 'The Department of Radiation Oncology，the Second Affiliated Hospital of Zhejiang University School of Medicine, hangzhou, zhejiang', 'geoPoint': {'lat': 30.29365, 'lon': 120.16142}}], 'centralContacts': [{'name': 'Ting Zhang, phD.', 'role': 'CONTACT', 'email': 'zezht@zju.edu.cn', 'phone': '+86-571-87783521'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Second Affiliated Hospital, School of Medicine, Zhejiang University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}