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

December 17, 2023 updated by: Zhimin Shao, Fudan University

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

139

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Cancer Hospital Affiliated to Fudan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LAR-HER2mut
If patients were LAR subtype with HER2 gene activated mutation
Drug: A1: Pyrotinib with nab-paclitaxel
A1: pyrotinib(EGFR-TKI) 400mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Other Names:
  • SHR1258
Drug: A2: nab-paclitaxel
A2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Experimental: LAR-PI3K/AKTmut
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 po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Drug: B2: nab-paclitaxel
B2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Experimental: IM
If patients were IM subtype (CD8 positive T cell more than 10%)
Drug: C1: PD-1 with nab-paclitaxel and famitinib
C1: PD-1 antibody SHR1210 200mg d1,15 ivgtt + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt + famitinib 20mg po qd, 4 weeks as a cycle
Other Names:
  • Camrelizumab
  • SHR1210
Drug: C2: nab-paclitaxel
C2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Experimental: BLIS/MES-PI3K/AKTWT
If patients were BLIS subtype or MES subtype without PI3K/AKT/mTOR pathway activation
Drug: D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabine
D1: VEGFR bevacizumab 10mg/kg d1,15 ivgtt + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle. Capecitabine with bevacizumab maintenance if intolerable toxicity was observed with no progression. Capecitabine maintenance 1000mg/m2 po bid d1-d14 every 3 weeks and bevacizumab 10mg/kg d1,15 ivgtt every 4 weeks.
Other Names:
  • Bevacizumab (BP102)
Drug: D2: nab-paclitaxel, with maintenance of capecitabine
D2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle. Capecitabine maintenance if intolerable toxicity was observed with no progression. Capecitabine maintenance 1000mg/m2 po bid d1-d14 every 3 weeks.
Experimental: MES-PI3K/AKTmut
If patients were MES subtype and had PI3K/AKT/mTOR pathway activation
Drug: E1: everolimus with nab-paclitaxel
E1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Drug: E2: nab-paclitaxel
E2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: approximately 3 years
Refers to the time between the patient's enrollment and any recorded tumor progression or death from any cause.
approximately 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: approximately 3 years
Refers to the period from the date of the first study dose to the date of death for any reason.
approximately 3 years
Objective response rate (ORR)
Time Frame: approximately 3 years
Defined as the proportion of patients whose tumors shrink to a certain amount and remain for a certain period of time, including cases of CR and PR.
approximately 3 years
Duration of Response (DoR)
Time Frame: approximately 3 years
Defined as the date from the first recording of tumor response (assessed according to RECIST 1.1) to the first recording of the objective progression of the tumor (assessed according to RECIST 1.1) or to the date of death for any reason, whichever occurs first.
approximately 3 years
Disease Control Rate (DCR)
Time Frame: approximately 3 years
The proportion of subjects who received treatment and whose best overall response (BOR) was assessed as complete response (CR), partial response (PR) and stable disease (SD) ≥4 weeks according to RECIST1.1.
approximately 3 years
Safety: Adverse Events (AE)
Time Frame: approximately 3 years
AE refers to any untoward medical occurrence in a study subject administered an investigational product which does not necessarily have a causal relationship with the treatment. AE is assessed according to the NCI-CTC AE 5.0.
approximately 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2020

Primary Completion (Actual)

May 31, 2023

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

May 15, 2020

First Submitted That Met QC Criteria

May 19, 2020

First Posted (Actual)

May 20, 2020

Study Record Updates

Last Update Posted (Actual)

December 22, 2023

Last Update Submitted That Met QC Criteria

December 17, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCHBCC-N031

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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