An Umbrella Trial Based on Molecular Pathway for Patients With Metastatic TNBC.

Phase 2

Active, not recruiting

Brief Summary: This is a Phase II, open-label, randomized controlled umbrella trial evaluating the efficacy and safety of multiple targeted treatment in patients with metastaticTNBC.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

ECOG Performance Status of 0-1
Expected lifetime of not less than three months
Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
Cancer stage: recurrent or metastatic breast cancer; Local recurrence be confirmed by the researchers could not be radical resection.
Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
Patients had received no previous chemotherapy or targeted therapy for metastatic triple-negative breast cancer
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm
Have the cognitive ability to understand the protocol and be willing to participate and to be followed up.

Exclusion Criteria

Symptomatic, untreated, or actively progressing CNS metastases
Active or history of autoimmune disease or immune deficiency
Active hepatitis B or hepatitis C
Significant cardiovascular disease
History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death
Treatment with taxel-based chemotherapy within 6 months
Treatment with chemotherapy, radiotherapy,immunotherapy or surgery (outpatient clinic surgery excluded)within3 weeks prior to initiation of study treatment.
Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Previous received anti-VEGFR small molecule tyrosine kinase inhibitors (e.g. famitinib, sorafenib, Sunitinib, regorafenib, etc.) for treatment of the patients .
A history of bleeding, any serious bleeding events.
Important blood vessels around tumors has been infringed and high risk of bleeding.
Long-term unhealing wound or incomplete healing of fracture
Urine protein ≥2+ and 24h urine protein quantitative > 1 g.
Arrhythmia for long-term use of anti-arrhythmic drugs and New York heart association class II or higher cardiac insufficiency

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	approximately 3 years	Refers to the time between the patient's enrollment and any recorded tumor progression or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	approximately 3 years	Refers to the period from the date of the first study dose to the date of death for any reason.
Objective response rate (ORR)	approximately 3 years	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.
Duration of Response (DoR)	approximately 3 years	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.
Disease Control Rate (DCR)	approximately 3 years	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.
Safety: Adverse Events (AE)	approximately 3 years	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.

Locations (1): Cancer Hospital Affiliated to Fudan University
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Shanghai, Shanghai, China