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

Primary Purpose

TNBC - Triple-Negative Breast Cancer

Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
A1: Pyrotinib with nab-paclitaxel
A2: nab-paclitaxel
B1: everolimus with nab-paclitaxel
B2: nab-paclitaxel
C1: PD-1 with nab-paclitaxel and famitinib
C2: nab-paclitaxel
D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabine
D2: nab-paclitaxel, with maintenance of capecitabine
E1: everolimus with nab-paclitaxel
E2: nab-paclitaxel
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for TNBC - Triple-Negative Breast Cancer focused on measuring TNBC, Molecular Subtype, Precision Treatment, Umbrella Trial, First Line

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

  • Cancer Hospital Affiliated to Fudan University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

LAR-HER2mut

LAR-PI3K/AKTmut

IM

BLIS/MES-PI3K/AKTWT

MES-PI3K/AKTmut

Arm Description

If patients were LAR subtype with HER2 gene activated mutation

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

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

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

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

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)
Refers to the time between the patient's enrollment and any recorded tumor progression or death from any cause.

Secondary Outcome Measures

Overall Survival (OS)
Refers to the period from the date of the first study dose to the date of death for any reason.
Objective response rate (ORR)
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.
Duration of Response (DoR)
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.
Disease Control Rate (DCR)
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.
Safety
Measured by adverse events, which 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.

Full Information

First Posted
May 15, 2020
Last Updated
October 15, 2023
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT04395989
Brief Title
An Umbrella Trial Based on Molecular Pathway for Patients With Metastatic TNBC.
Acronym
FUTURE-SUPER
Official Title
An Umbrella Trial Based on Molecular Pathway for Patients With Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer (FUTURE SUPER)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 28, 2020 (Actual)
Primary Completion Date
November 15, 2023 (Anticipated)
Study Completion Date
November 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
TNBC - Triple-Negative Breast Cancer
Keywords
TNBC, Molecular Subtype, Precision Treatment, Umbrella Trial, First Line

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
139 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LAR-HER2mut
Arm Type
Experimental
Arm Description
If patients were LAR subtype with HER2 gene activated mutation
Arm Title
LAR-PI3K/AKTmut
Arm Type
Experimental
Arm Description
If patients were LAR subtype without HER2 gene activated mutation, but had PI3K/AKT/mTOR pathway mutation
Arm Title
IM
Arm Type
Experimental
Arm Description
If patients were IM subtype (CD8 positive T cell more than 10%)
Arm Title
BLIS/MES-PI3K/AKTWT
Arm Type
Experimental
Arm Description
If patients were BLIS subtype or MES subtype without PI3K/AKT/mTOR pathway activation
Arm Title
MES-PI3K/AKTmut
Arm Type
Experimental
Arm Description
If patients were MES subtype and had PI3K/AKT/mTOR pathway activation
Intervention Type
Drug
Intervention Name(s)
A1: Pyrotinib with nab-paclitaxel
Other Intervention Name(s)
SHR1258
Intervention Description
A1: pyrotinib(EGFR-TKI) 400mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Intervention Type
Drug
Intervention Name(s)
A2: nab-paclitaxel
Intervention Description
A2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Intervention Type
Drug
Intervention Name(s)
B1: everolimus with nab-paclitaxel
Intervention Description
B1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Intervention Type
Drug
Intervention Name(s)
B2: nab-paclitaxel
Intervention Description
B2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Intervention Type
Drug
Intervention Name(s)
C1: PD-1 with nab-paclitaxel and famitinib
Other Intervention Name(s)
Camrelizumab, SHR1210
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
C2: nab-paclitaxel
Intervention Description
C2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Intervention Type
Drug
Intervention Name(s)
D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabine
Other Intervention Name(s)
Bevacizumab (BP102)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
D2: nab-paclitaxel, with maintenance of capecitabine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
E1: everolimus with nab-paclitaxel
Intervention Description
E1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Intervention Type
Drug
Intervention Name(s)
E2: nab-paclitaxel
Intervention Description
E2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
Refers to the time between the patient's enrollment and any recorded tumor progression or death from any cause.
Time Frame
approximately 3 years
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Refers to the period from the date of the first study dose to the date of death for any reason.
Time Frame
approximately 3 years
Title
Objective response rate (ORR)
Description
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.
Time Frame
approximately 3 years
Title
Duration of Response (DoR)
Description
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.
Time Frame
approximately 3 years
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
approximately 3 years
Title
Safety
Description
Measured by adverse events, which 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.
Time Frame
approximately 3 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Cancer Hospital Affiliated to Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China

12. IPD Sharing Statement

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An Umbrella Trial Based on Molecular Pathway for Patients With Metastatic TNBC.

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