FUSCC Refractory TNBC Umbrella (FUTURE)

Phase 1

• Conditions: Triple-negative Breast Cancer
• Interventions: Drug: MES with anti-VEGFR included therapy; Drug: Pyrotinib with Capecitabine; Drug: AR inhibitor combined with everolimus(B1) or CDK4/6 inhibitor(B2),or EZH2 inhibitor (B4); Drug: PARP inhibitor included therapy; Drug: anti PD-1 with nab-paclitaxel; Drug: BLIS with anti-VEGFR included therapy; Drug: mTOR inhibitor with nab-paclitaxel

• Registration Number: NCT03805399
• Lead Sponsor: Fudan University

Brief Summary

This is a Phase Ib/II, open-label, multi-center umbrella study evaluating the efficacy and safety of multiple targeted treatment in patients with refractory metastatic TNBC.The specific grouping of patients' depends on FUSCC 500+ gene panel testing and IHC subtype staining.

Detailed Description

This is a Phase Ib/II, open-label, multi-center,umbrella study evaluating the efficacy and safety of multiple targeted treatment in patients with metastatic TNBC who had disease progression during or following standard treatment with chemotherapy(anthracyclines,taxanes,platinums, vinorelbine,capecitabine,and gemcitabine included).300-400 patients will be screened and eligible participants will enter different treatment arms according to their molecular subtype (IHC staining) and FUSCC 500+ gene panel testing results. 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.New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-10-18
• Study First Submitted: 2019-01-08
• Study First Submitted QC: 2019-01-13
• Study First Posted: 2019-01-15
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-08
• Last Update Posted: 2022-08-10
• Primary Completion: 2022-12-01
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 140

Inclusion Criteria

• ECOG Performance Status of 0, 1, or 2
• Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
• Radiologic/objective evidence of recurrence or disease progression after available standard chemotherapy regimens(anthracyclines,taxanes, platinums, vinorelbine,capacitabine, and gemcitabine included) for metastatic breast cancer(MBC)
• Availability of a representative tumor specimen that is suitable for rebiopsy, IHC staining and gene sequencing
• Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm
• Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
• have the cognitive ability to understand the protocol and be willing to participate and to be followed up.

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Exclusion Criteria

• Symptomatic, untreated, or actively progressing CNS metastases
• Active or history of autoimmune disease or immune deficiency
• 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 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MES with anti-VEGFR included therapy	MES with anti-VEGFR included therapy	If patients were MES subtype and without PI3K/AKT pathway activation
pyrotinib with capecitabine	Pyrotinib with Capecitabine	If patients were LAR subtype with HER2 gene activated mutation
AR inhibitor with CDK4/6 inhibitor	AR inhibitor combined with everolimus(B1) or CDK4/6 inhibitor(B2),or EZH2 inhibitor (B4)	If patients were LAR subtype without HER2 gene activated mutation, but had PIK3CA mutation, enter into arm B1; If patients were LAR subtype without HER2 gene activated mutation or PIK3CA mutation, enter into arm B2;If B2 was closed, enter into B4;
PARP inhibitor included therapy	PARP inhibitor included therapy	If patients were BLIS subtype and had a BRCA gene pathogenic mutation
anti PD-1 with nab-paclitaxel	anti PD-1 with nab-paclitaxel	If patients were IM subtype(CD8 positive T cell more than 20%)
BLIS with anti-VEGFR included therapy	BLIS with anti-VEGFR included therapy	If patients were BLIS subtype and did not have a BRCA gene pathogenic mutation
mTOR inhibitor with nab-paclitaxel	mTOR inhibitor with nab-paclitaxel	If patients were MES subtype and had PI3K/AKT pathway activation

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 3 years)	The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate(DOR)	Baseline through end of study (approximately 3 years)	Complete remission or partial remission or stable disease (according to RECIST1.1)
Progression Free Survival(PFS)	Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 3 years)	time to progressive disease (according to RECIST1.1)
Overall Survival (OS)	Randomization to death from any cause, through the end of study (approximately 3 years)	time to death due to any cause

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China