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This is a Phase II, open-label, randomized controlled umbrella trial evaluating the efficacy and safety of multiple targeted treatment in patients with metastaticTNBC.
This is a Phase II, open-label, randomized controlled umbrella trial evaluating the efficacy and safety of multiple targeted treatment vs. traditional chemotherapy in patients with unresectable locally advanced or metastatic triple negative breast cancer. The specific grouping of patients' depends on FUSCC 500+ gene panel testing and IHC subtype staining.These tests would be done on their rebiopsy tumor specimen. Specifically, as to TNBC molecular subtyping,FUSCC data identified the genomic aberrations that drive each TNBC subtype by applying an integrative analysis combining somatic mutation, copy number aberrations (CNAs) and gene expression profiles, which classified TNBC patients into four subtypes, namely luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immune suppressed (BLIS), and mesenchymal-like (MES). Then, FUSCC conducted a IHC subtyping model to replace complex genomic sequencing, which have been validated in FUSCC cohort.FUSCC 500+ gene panel was developed combining public database(TCGA, METABRIC, 560WES, MSKCC-IMPACT ect.) and FUSCC private TNBC database.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LAR-HER2mut | Experimental | If patients were LAR subtype with HER2 gene activated mutation |
|
| LAR-PI3K/AKTmut | Experimental | If patients were LAR subtype without HER2 gene activated mutation, but had PI3K/AKT/mTOR pathway mutation |
|
| IM | Experimental | If patients were IM subtype (CD8 positive T cell more than 10%) |
|
| BLIS/MES-PI3K/AKTWT | Experimental | If patients were BLIS subtype or MES subtype without PI3K/AKT/mTOR pathway activation |
|
| MES-PI3K/AKTmut | Experimental | If patients were MES subtype and had PI3K/AKT/mTOR pathway activation |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| A1: Pyrotinib with nab-paclitaxel | Drug | A1: pyrotinib(EGFR-TKI) 400mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | Refers to the time between the patient's enrollment and any recorded tumor progression or death from any cause. | approximately 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | Refers to the period from the date of the first study dose to the date of death for any reason. | approximately 3 years |
| Objective response rate (ORR) | Defined as the proportion of patients whose tumors shrink to a certain amount and remain for a certain period of time, including cases of CR and PR. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Hospital Affiliated to Fudan University | Shanghai | Shanghai Municipality | 200032 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38211606 | Derived | Fan L, Wang ZH, Ma LX, Wu SY, Wu J, Yu KD, Sui XY, Xu Y, Liu XY, Chen L, Zhang WJ, Jin X, Xiao Q, Shui RH, Xiao Y, Wang H, Yang YS, Huang XY, Cao AY, Li JJ, Di GH, Liu GY, Yang WT, Hu X, Xia Y, Liang QN, Jiang YZ, Shao ZM. Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial. Lancet Oncol. 2024 Feb;25(2):184-197. doi: 10.1016/S1470-2045(23)00579-X. Epub 2024 Jan 8. |
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| A2: nab-paclitaxel | Drug | A2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle |
|
| B1: everolimus with nab-paclitaxel | Drug | B1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle |
|
| B2: nab-paclitaxel | Drug | B2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle |
|
| C1: PD-1 with nab-paclitaxel and famitinib | Drug | C1: PD-1 antibody SHR1210 200mg d1,15 ivgtt + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt + famitinib 20mg po qd, 4 weeks as a cycle |
|
|
| C2: nab-paclitaxel | Drug | C2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle |
|
| D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabine | Drug | D1: VEGFR bevacizumab 10mg/kg d1,15 ivgtt + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle. Capecitabine with bevacizumab maintenance if intolerable toxicity was observed with no progression. Capecitabine maintenance 1000mg/m2 po bid d1-d14 every 3 weeks and bevacizumab 10mg/kg d1,15 ivgtt every 4 weeks. |
|
|
| D2: nab-paclitaxel, with maintenance of capecitabine | Drug | D2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle. Capecitabine maintenance if intolerable toxicity was observed with no progression. Capecitabine maintenance 1000mg/m2 po bid d1-d14 every 3 weeks. |
|
| E1: everolimus with nab-paclitaxel | Drug | E1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle |
|
| E2: nab-paclitaxel | Drug | E2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle |
|
| approximately 3 years |
| Duration of Response (DoR) | Defined as the date from the first recording of tumor response (assessed according to RECIST 1.1) to the first recording of the objective progression of the tumor (assessed according to RECIST 1.1) or to the date of death for any reason, whichever occurs first. | approximately 3 years |
| Disease Control Rate (DCR) | The proportion of subjects who received treatment and whose best overall response (BOR) was assessed as complete response (CR), partial response (PR) and stable disease (SD) ≥4 weeks according to RECIST1.1. | approximately 3 years |
| Safety: Adverse Events (AE) | AE refers to any untoward medical occurrence in a study subject administered an investigational product which does not necessarily have a causal relationship with the treatment. AE is assessed according to the NCI-CTC AE 5.0. | approximately 3 years |
| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C520255 | 130-nm albumin-bound paclitaxel |
| C584390 | famitinib |
| C000631724 | camrelizumab |
| D000069287 | Capecitabine |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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