Clinical Trials /

FUSCC Refractory TNBC Umbrella (FUTURE)

NCT03805399

Description:

This is a Phase Ib/II, open-label, 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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: FUSCC Refractory TNBC Umbrella (FUTURE)
  • Official Title: Precision Treatment of Refractory Triple Negative Breast Cancer Based on Molecular Subtyping --FUSCC-TNBC- Umbrella Trial

Clinical Trial IDs

  • ORG STUDY ID: 1807188-16
  • NCT ID: NCT03805399

Conditions

  • Triple-negative Breast Cancer

Interventions

DrugSynonymsArms
Pyrotinib with CapecitabineSHR1258pyrotinib with capecitabine
AR inhibitor with CDK4/6 inhibitorSHR3680 SHR6390AR inhibitor with CDK4/6 inhibitor
anti PD-1 with nab-paclitaxelSHR1210anti PD-1 with nab-paclitaxel
PARP inhibitor included therapySHR3162PARP inhibitor included therapy
BLIS with anti-VEGFR included therapyYN968D1BLIS with anti-VEGFR included therapy
MES with anti-VEGFR included therapyYN968D1MES with anti-VEGFR included therapy
mTOR inhibitor with nab-paclitaxeleverolimusmTOR inhibitor with nab-paclitaxel

Purpose

This is a Phase Ib/II, open-label, 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, 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.
    

Trial Arms

NameTypeDescriptionInterventions
pyrotinib with capecitabineExperimentalIf patients were LAR subtype with HER2 gene activated mutation
  • Pyrotinib with Capecitabine
AR inhibitor with CDK4/6 inhibitorExperimentalIf 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
  • AR inhibitor with CDK4/6 inhibitor
anti PD-1 with nab-paclitaxelExperimentalIf patients were IM subtype(CD8 positive T cell more than 20%)
  • anti PD-1 with nab-paclitaxel
PARP inhibitor included therapyExperimentalIf patients were BLIS subtype and had a BRCA gene pathogenic mutation
  • PARP inhibitor included therapy
BLIS with anti-VEGFR included therapyExperimentalIf patients were BLIS subtype and did not have a BRCA gene pathogenic mutation
  • BLIS with anti-VEGFR included therapy
MES with anti-VEGFR included therapyExperimentalIf patients were MES subtype and without PI3K/AKT pathway activation
  • MES with anti-VEGFR included therapy
mTOR inhibitor with nab-paclitaxelExperimentalIf patients were MES subtype and had PI3K/AKT pathway activation
  • mTOR inhibitor with nab-paclitaxel

Eligibility Criteria

        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.

        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
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame: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)
Safety Issue:
Description:The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

Secondary Outcome Measures

Measure:Disease Control Rate(DOR)
Time Frame:Baseline through end of study (approximately 3 years)
Safety Issue:
Description:Complete remission or partial remission or stable disease (according to RECIST1.1)
Measure:Progression Free Survival(PFS)
Time Frame: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)
Safety Issue:
Description:time to progressive disease (according to RECIST1.1)
Measure:Overall Survival (OS)
Time Frame:Randomization to death from any cause, through the end of study (approximately 3 years)
Safety Issue:
Description:time to death due to any cause

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fudan University

Trial Keywords

  • TNBC
  • Molecular Subtype
  • Precision Treatment
  • Umbrella

Last Updated

January 30, 2020