FUTURE-SUPER: An Umbrella Trial Based on Molecular Pathway for Patients With Metastatic TNBC.

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04395989

Collaborator

(none)

138

Enrollment

Location

Arms

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
TNBC - Triple-Negative Breast Cancer	Drug: A1: Pyrotinib with Capecitabine Drug: A2: nab-paclitaxel Drug: B1: everolimus with nab-paclitaxel Drug: B2: nab-paclitaxel Drug: C1: PD-1 with nab-paclitaxel and famitinib Drug: C2: nab-paclitaxel Drug: D1: VEGFR and nab-paclitaxel Drug: D2: nab-paclitaxel Drug: E1: Everolimus with nab-paclitaxel Drug: E2: nab-paclitaxel	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

138 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 15, 2020

Anticipated Primary Completion Date :

Nov 15, 2022

Anticipated Study Completion Date :

Nov 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LAR-HER2+ If patients were LAR subtype with HER2 gene activated mutation	Drug: A1: Pyrotinib with Capecitabine A1: pyrotinib(EGFR-TKI) 400mg qd and capecitabine 1000mg/m2 bid (d1-d14) Other Names: SHR1258 Drug: A2: nab-paclitaxel A2: nab-paclitaxel 100mg qw (three week on one week off)
Experimental: LAR-PAM+ If patients were LAR subtype without HER2 gene activated mutation, but had PI3K/AKT/mTOR pathway mutation	Drug: B1: everolimus with nab-paclitaxel B1: everolimus 10mg qd combined with nab-paclitaxel 100mg qw (three week on one week off) Drug: B2: nab-paclitaxel B2: nab-paclitaxel 100mg qw (three week on one week off)
Experimental: IM If patients were IM subtype (CD8 positive T cell more than 20%)	Drug: C1: PD-1 with nab-paclitaxel and famitinib C1: PD-1 antibody SHR1210 200mg q2w and nab-paclitaxel 100mg qw (three week on one week off) and famitinib 20mg qd Other Names: Camrelizumab SHR1210 Drug: C2: nab-paclitaxel C2: nab-paclitaxel 100mg qw (three week on one week off)
Experimental: BLIS If patients were BLIS subtype or MES subtype and without PI3K/AKT/mTOR pathway activation	Drug: D1: VEGFR and nab-paclitaxel D1: VEGFR BP102 10mg/kg q2w and nab-paclitaxel 100mg qw (three week on one week off). Other Names: BP102 Drug: D2: nab-paclitaxel D2: nab-paclitaxel 100mg qw (three week on one week off)
Experimental: MES-PAM+ If patients were MES subtype and had PI3K/AKT/mTOR pathway activation	Drug: E1: Everolimus with nab-paclitaxel E1: Everolimus 10mg qd with nab-paclitaxel 100mg qw (three week on one week off) Drug: E2: nab-paclitaxel E2: nab-paclitaxel 100mg qw (three week on one week off)

Outcome Measures

Primary Outcome Measures

PFS of Each Arm [approximately 3 years]
Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study time to progressive disease (according to RECIST1.1) of each arm
PFS of Precision Treatment [approximately 3 years]
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 of precision treatment

Secondary Outcome Measures

OS of Each Arm [approximately 3 years]
Randomization to death from any cause, through the end of study of Each Arm
OS of Precision Treatment [approximately 3 years]
Randomization to death from any cause, through the end of study of Precision Treatment
Objective Response Rate [approximately 3 years]
Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 in all Participants

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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