The Optimal Radioimmunotherapy Combinations for Advanced TNBC
- Conditions
- Interventions
- Radiation: radiotehrapy 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (total 8Gy)Radiation: radiotherapy 5 Gy × 5 fractions, once a dayRadiation: radiotherapy 8 Gy × 5 fractions, once a dayRadiation: radiotherapy 8 Gy × 3 fractions, once every other dayRadiation: radiotherapy 10 Gy× 3 fractions, once every other dayDrug: ToripalimabDrug: chemotherapy regimen selected by the investigator
- Registration Number
- NCT06735131
- Lead Sponsor
- Sun Yat-sen University
- Brief Summary
This study aims to explore the best combination patterns of radiotherapy and immunotherapy for advanced triple-negative breast cancer (TNBC).
- Detailed Description
Metastatic triple-negative breast cancer (mTNBC) is a particularly aggressive form of breast cancer that poses significant therapeutic challenges. Because mTNBC tumors do not express estrogen receptors (ER), progesterone receptors (PR), or HER2, patients with this subtype cannot receive benefits from endocrine therapy or HER2-targeted treatments, leaving che...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
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Inoperable locally advanced/metastatic triple-negative breast cancer (defined as ER and PR <1%; and HER2 negative as IHC 0 or IHC 1+, or IHC 2+ but negative upon fluorescence in situ hybridization (FISH) testing).
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No prior chemotherapy for advanced/metastatic disease.
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ECOG PS score of 0 or 1.
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Presence of 1 to 5 tumor lesions, with individual lesion size between 0.5 and 5 cm, not limited to 1 to 2 organs.
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At least one lesion suitable for radiotherapy.
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Suitable to receive one of the chemotherapy regimens chosen by the investigator: nab-paclitaxel or gemcitabine + carboplatin.
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Patients with only bone metastases are allowed to enroll.
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Patients who have previously received PD-1/PD-L1 therapy for early-stage disease are allowed to enroll.
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Able to provide tumor tissue sections or agree to tumor biopsy during the screening period.
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Adequate organ and bone marrow function, with specific requirements:
- Hematology: Neutrophil count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥90×10^9/L; Hemoglobin (Hb) ≥90 g/L; No blood product transfusion (including red blood cell and platelet products, etc.) or growth factor (including colony-stimulating factors, interleukins, and erythropoietin, etc.) support treatment within 2 weeks prior to examination.
- Liver function: Serum total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (for patients with liver metastases: ALT and AST ≤5×ULN).
- Renal function: Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance >60 mL/min.
- Received platinum-containing regimens during the adjuvant/neoadjuvant therapy phase, and the interval from the last treatment to recurrence/metastasis is less than 6 months.
- Have received radiotherapy within 12 weeks prior to enrollment, unless the radiotherapy was for adjuvant purposes and there are lesions outside the previously irradiated field.
- Extensive tumor metastasis with surrounding normal tissues that cannot tolerate radiotherapy damage.
- Patients with central nervous system metastases.
- Significant third-space fluid retention (e.g., ascites, pleural effusion, pericardial effusion).
- Require long-term systemic corticosteroid treatment.
- Have active autoimmune diseases.
- Have concurrent severe infections.
- Other patients deemed unsuitable for enrollment by the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 4: 10Gy × 3, every other day chemotherapy regimen selected by the investigator within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 5: 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (8 Gy in total) radiotehrapy 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (total 8Gy) on the first 2 days of first 4 cycles of toripalimab and chemotherapy Arm 5: 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (8 Gy in total) Toripalimab on the first 2 days of first 4 cycles of toripalimab and chemotherapy Arm 1: 5Gy × 5 , daily radiotherapy 5 Gy × 5 fractions, once a day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 1: 5Gy × 5 , daily Toripalimab within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 1: 5Gy × 5 , daily chemotherapy regimen selected by the investigator within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 2: 8Gy × 5 , daily radiotherapy 8 Gy × 5 fractions, once a day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 2: 8Gy × 5 , daily Toripalimab within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 2: 8Gy × 5 , daily chemotherapy regimen selected by the investigator within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 3: 8Gy × 3, every other day radiotherapy 8 Gy × 3 fractions, once every other day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 3: 8Gy × 3, every other day Toripalimab within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 5: 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (8 Gy in total) chemotherapy regimen selected by the investigator on the first 2 days of first 4 cycles of toripalimab and chemotherapy Arm 3: 8Gy × 3, every other day chemotherapy regimen selected by the investigator within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 4: 10Gy × 3, every other day radiotherapy 10 Gy× 3 fractions, once every other day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy Arm 4: 10Gy × 3, every other day Toripalimab within 4 weeks before the initiation of cycle of toripalimab and chemotherapy
- Primary Outcome Measures
Name Time Method Progression-free survival at 6 months (6m-PFS rate) 6 months Progression-free survival at 6 months (6m-PFS rate) is defined as the percentage of patients who have not experienced disease progression or death due to any cause at the 6-month mark after starting treatment.
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) Up to 3 years Progression-free survival (PFS) is defined as the time from treatment initiation to disease progression or death from any cause.
Overall survival (OS) up to 3 years Overall survival (OS) is defined as the time from treatment initiation to death from any cause.
Objective Response Rate up to 3 years Objective response rate (ORR) is defined as the percetage of patients achieving a complete response (CR) or partial response (PR) according to RECIST v.1.1.
Duration of response up to 3 years Duration of response (DOR) is defined as the duration from response initiation (when either CR or PR is first determined) to progression or death, whichever occurs first.
Number of participants with treatment-related adverse events up to 3 years Adverse events are assessed by CTCAE v5.0