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

Fudan University

Status and phase: Active, not recruiting; Phase 2

Conditions: TNBC - Triple-Negative Breast Cancer

Treatments: Drug: C1: PD-1 with nab-paclitaxel and famitinib; Drug: A2: nab-paclitaxel; Drug: B1: everolimus with nab-paclitaxel; Drug: E1: everolimus with nab-paclitaxel; Drug: C2: nab-paclitaxel; Drug: B2: nab-paclitaxel; Drug: D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabine; Drug: D2: nab-paclitaxel, with maintenance of capecitabine; Drug: E2: nab-paclitaxel; Drug: A1: Pyrotinib with nab-paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT04395989

SCHBCC-N031

Details and patient eligibility

About

This is a Phase II, open-label, randomized controlled umbrella trial evaluating the efficacy and safety of multiple targeted treatment in patients with metastaticTNBC.

Full 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.

Enrollment: 139 patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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139 participants in 5 patient groups

LAR-HER2mut

Experimental group

Description:

If patients were LAR subtype with HER2 gene activated mutation

Treatment:

Drug: A2: nab-paclitaxel

Drug: A1: Pyrotinib with nab-paclitaxel

LAR-PI3K/AKTmut

Experimental group

Description:

If patients were LAR subtype without HER2 gene activated mutation, but had PI3K/AKT/mTOR pathway mutation

Treatment:

Drug: B2: nab-paclitaxel

Drug: B1: everolimus with nab-paclitaxel

IM

Experimental group

Description:

If patients were IM subtype (CD8 positive T cell more than 10%)

Treatment:

Drug: C1: PD-1 with nab-paclitaxel and famitinib

Drug: C2: nab-paclitaxel

BLIS/MES-PI3K/AKTWT

Experimental group

Description:

If patients were BLIS subtype or MES subtype without PI3K/AKT/mTOR pathway activation

Treatment:

Drug: D2: nab-paclitaxel, with maintenance of capecitabine

Drug: D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabine

MES-PI3K/AKTmut

Experimental group

Description:

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

Treatment:

Drug: E1: everolimus with nab-paclitaxel

Drug: E2: nab-paclitaxel