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

TNBC - Triple-Negative Breast Cancer Clinical Trial

— FUTURE-SUPER  

Official title:

An Umbrella Trial Based on Molecular Pathway for Patients With Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer (FUTURE SUPER)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04395989
• Other study ID #: SCHBCC-N031
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 28, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 139
• Est. completion date: December 31, 2024
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

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

Related Conditions & MeSH terms

• Breast Neoplasms
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• A1: Pyrotinib with nab-paclitaxel
A1: pyrotinib(EGFR-TKI) 400mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• A2: nab-paclitaxel
A2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• B1: everolimus with nab-paclitaxel
B1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• B2: nab-paclitaxel
B2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• C1: PD-1 with nab-paclitaxel and famitinib
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
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
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
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
E1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• E2: nab-paclitaxel
E2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

Locations

Country	Name	City	State
China	Cancer Hospital Affiliated to Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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
Secondary	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.	approximately 3 years
Secondary	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
Secondary	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
Secondary	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