Clinical trial NCT04395989: An Umbrella Trial Based on Molecular Pathway for Patients With Metastatic TNBC.
Official title: An Umbrella Trial Based on Molecular Pathway for Patients With Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer (FUTURE SUPER)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: TNBC - Triple-Negative Breast Cancer
Keywords: TNBC
Molecular Subtype
Precision Treatment
Umbrella Trial
First Line
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-05-20
Enrollment: 139
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 outcomes:
measure: Progression Free Survival (PFS)
timeFrame: approximately 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: approximately 3 years
measure: Objective response rate (ORR)
timeFrame: approximately 3 years
measure: Duration of Response (DoR)
timeFrame: approximately 3 years
measure: Disease Control Rate (DCR)
timeFrame: approximately 3 years
measure: Safety: Adverse Events (AE)
timeFrame: approximately 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Cancer Hospital Affiliated to Fudan University
state: Shanghai
Study officials:
References: