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.
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
| Drug | Synonyms | Arms |
|---|
| Pyrotinib with Capecitabine | SHR1258 | pyrotinib with capecitabine |
| AR inhibitor with CDK4/6 inhibitor | SHR3680 SHR6390 | AR inhibitor with CDK4/6 inhibitor |
| anti PD-1 with nab-paclitaxel | SHR1210 | anti PD-1 with nab-paclitaxel |
| PARP inhibitor included therapy | SHR3162 | PARP inhibitor included therapy |
| BLIS with anti-VEGFR included therapy | YN968D1 | BLIS with anti-VEGFR included therapy |
| MES with anti-VEGFR included therapy | YN968D1 | MES with anti-VEGFR included therapy |
| mTOR inhibitor with nab-paclitaxel | everolimus | mTOR 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
| Name | Type | Description | Interventions |
|---|
| pyrotinib with capecitabine | Experimental | If patients were LAR subtype with HER2 gene activated mutation | - 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 | - AR inhibitor with CDK4/6 inhibitor
|
| anti PD-1 with nab-paclitaxel | Experimental | If patients were IM subtype(CD8 positive T cell more than 20%) | - anti PD-1 with nab-paclitaxel
|
| PARP inhibitor included therapy | Experimental | If patients were BLIS subtype and had a BRCA gene pathogenic mutation | - 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 | - BLIS with anti-VEGFR included therapy
|
| MES with anti-VEGFR included therapy | Experimental | If patients were MES subtype and without PI3K/AKT pathway activation | - MES with anti-VEGFR included therapy
|
| mTOR inhibitor with nab-paclitaxel | Experimental | If 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
February 5, 2020
