FUSCC Refractory TNBC Umbrella (FUTURE)

NCT03805399 | Unknown Phase 1

• 1 other identifier: 1807188-16
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Triple-negative Breast Cancer

Keywords

TNBC; Molecular Subtype; Precision Treatment; Umbrella

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

  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)

Secondary Outcomes (3)

• Disease Control Rate(DOR)

  Baseline through end of study (approximately 3 years)

• 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)

• Overall Survival (OS)

  Randomization to death from any cause, through the end of study (approximately 3 years)

Study Arms (7)

pyrotinib with capecitabine

EXPERIMENTAL

If patients were LAR subtype with HER2 gene activated mutation

Drug: Pyrotinib with Capecitabine

AR inhibitor with CDK4/6 inhibitor

EXPERIMENTAL

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;

Drug: AR inhibitor combined with everolimus(B1) or CDK4/6 inhibitor(B2),or EZH2 inhibitor (B4)

anti PD-1 with nab-paclitaxel

EXPERIMENTAL

If patients were IM subtype(CD8 positive T cell more than 20%)

Drug: anti PD-1 with nab-paclitaxel

PARP inhibitor included therapy

EXPERIMENTAL

If patients were BLIS subtype and had a BRCA gene pathogenic mutation

Drug: PARP inhibitor included therapy

BLIS with anti-VEGFR included therapy

EXPERIMENTAL

If patients were BLIS subtype and did not have a BRCA gene pathogenic mutation

Drug: BLIS with anti-VEGFR included therapy

MES with anti-VEGFR included therapy

EXPERIMENTAL

If patients were MES subtype and without PI3K/AKT pathway activation

Drug: MES with anti-VEGFR included therapy

mTOR inhibitor with nab-paclitaxel

EXPERIMENTAL

If patients were MES subtype and had PI3K/AKT pathway activation

Drug: mTOR inhibitor with nab-paclitaxel

Interventions

Pyrotinib with Capecitabine DRUG

If patients were LAR subtype with HER2 gene activated mutation, she would receive pyrotinib(EGFR-TKI) 400mg qd and capecitabine 1000mg/m2 bid (d1-d14)

Also known as: SHR1258

pyrotinib with capecitabine

AR inhibitor combined with everolimus(B1) or CDK4/6 inhibitor(B2),or EZH2 inhibitor (B4) DRUG

B1: if patients were LAR subtype without HER2 gene activated mutation, but had PI3KCA mutation, she would receive everolimus 10mg qd combined with AR inhibitor SHR3680 240mg qd continuously ; B2: if patients were LAR subtype without HER2 gene activated mutation or PI3KCA mutation, she would receive AR inhibitor SHR3680 240mg qd combined with CDK4/6 inhibitor SHR6390 150mg qd (three week on one week off); B4: If patients were LAR subtype without HER2 gene activated mutation or PI3KCA mutation, she would receive AR inhibitor SHR3680 240mg qd combined with EZH2 inhibitor SHR2554 300mg bid continuously

Also known as: SHR3680 SHR6390

AR inhibitor with CDK4/6 inhibitor

anti PD-1 with nab-paclitaxel DRUG

If patients were IM subtype, she will receive PD-1 antibody SHR1210 200mg q2w and nab-paclitaxel 100mg qw (three week on one week off).

Also known as: SHR1210

anti PD-1 with nab-paclitaxel

PARP inhibitor included therapy DRUG

If patients were BLIS subtype and had a BRCA gene pathogenic mutation, she will receive PARP inhibitor SHR3162 150mg bid and famitinib 20mg qd continuously .

Also known as: SHR3162

PARP inhibitor included therapy

BLIS with anti-VEGFR included therapy DRUG

If patients were BLIS subtype and did not have a BRCA gene pathogenic mutation , she will receive: E2: apatinib 250mg qd continuously combined with VP-16 50mg qd (three week on one week off); E3: famitinib 20mg qd continuously combined with VP-16 50mg qd (three week on one week off); E4: BP102 10mg/kg d1,d15 combined with nab-paclitaxel 100mg d1,d8,d,15; q4w

Also known as: YN968D1

BLIS with anti-VEGFR included therapy

MES with anti-VEGFR included therapy DRUG

If patients were MES subtype and without PI3K/AKT pathway activation,she will receive famitinib 20mg qd continuously combined with VP-16 50mg qd (three week on one week off).

Also known as: YN968D1

MES with anti-VEGFR included therapy

mTOR inhibitor with nab-paclitaxel DRUG

If patients were MES subtype and had PI3K/AKT pathway activation, she will receive mTOR inhibitor 10mg qd continuously combined with nab-paclitaxel 100mg qw (three week on one week off).

Also known as: everolimus

mTOR inhibitor with nab-paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (3)

• Liu CC, Chen L, Cai YW, Chen YF, Liu YM, Zhou YJ, Shao ZM, Yu KD. Targeting EMSY-mediated methionine metabolism is a potential therapeutic strategy for triple-negative breast cancer. Cell Rep Med. 2024 Feb 20;5(2):101396. doi: 10.1016/j.xcrm.2024.101396. Epub 2024 Jan 29.

  PMID: 38290515 DERIVED

• Xiao Y, Ma D, Yang YS, Yang F, Ding JH, Gong Y, Jiang L, Ge LP, Wu SY, Yu Q, Zhang Q, Bertucci F, Sun Q, Hu X, Li DQ, Shao ZM, Jiang YZ. Comprehensive metabolomics expands precision medicine for triple-negative breast cancer. Cell Res. 2022 May;32(5):477-490. doi: 10.1038/s41422-022-00614-0. Epub 2022 Feb 1.

  PMID: 35105939 DERIVED

• Jiang YZ, Liu Y, Xiao Y, Hu X, Jiang L, Zuo WJ, Ma D, Ding J, Zhu X, Zou J, Verschraegen C, Stover DG, Kaklamani V, Wang ZH, Shao ZM. Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial. Cell Res. 2021 Feb;31(2):178-186. doi: 10.1038/s41422-020-0375-9. Epub 2020 Jul 27.

  PMID: 32719455 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

pyrotinib; Capecitabine; 130-nm albumin-bound paclitaxel; camrelizumab; fluzoparib; apatinib; Sirolimus; Everolimus

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Macrolides; Lactones; Organic Chemicals

Study Officials

• Zhimin U Shao, Professor

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhimin U Shao, Professor

CONTACT

86-021-64175590; zhimingshao@yahoo.com

Zhonghua U Wang,Professor

CONTACT

86-021-64175590; zhonghuawang95@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The refractory mTNBC participants will be classified into four subtypes based on immunohistochemistry tests namely luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immune suppressed (BLIS), and mesenchymal (MES).Then according to gene sequencing outcomes, different subtypes would receive different targeted therapy (combined with chemotherapy in three treatment arms).

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 15, 2019
• Study Start: October 18, 2018
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: August 10, 2022

Record last verified: 2022-08

Locations

CN (1)