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FUSCC Refractory TNBC Platform Study (FUTURE2.0)

Primary Purpose

Triple-negative Breast Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
A1: SHR-A1811
A2: SHR-A1811 with Camrelizumab
B1: TROP2 ADC
B2: TROP2 ADC with Camrelizumab
C1: SHR-A1811
C2: SHR-A1811 with BP102
D1: TROP2 ADC
D2: TROP2 ADC with BP102
E1: SHR-A1811
F1: TROP2 ADC
G1: SHR-A1811
H1: TROP2 ADC
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple-negative Breast Cancer focused on measuring TNBC, Molecular Subtype, Precision Treatment, Platform Study

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Female aged ≥18 years; TNBC invasive breast cancer confirmed by histology (specific definition: ER <1% positive tumor cells by immunohistochemistry is defined as ER negative, PR <1% positive tumor cells is defined as PR negative, HER2 0-1+ or HER2 ++ but negative by FISH without amplification was defined as HER2 negative); Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer; Progression after at least two prior therapeutic regimens for advanced/metastatic TNBC At least one measurable lesion according to RECIST 1.1 (conventional CT scan ≥20 mm, spiral CT scan ≥10 mm, measurable lesion has not received radiotherapy); The functions of the main organs are basically normal and meet the following conditions: i. Blood routine examination criteria shall meet: HB ≥90 g/L (no blood transfusion within 14 days); The ANC acuity 1.5 x 109 / L; PLT acuity 75 x 109 / L; ii. Biochemical tests should meet the following criteria: TBIL ≤1.5×ULN (upper limit of normal value); ALT and AST ≤3×ULN; If liver metastases were present, ALT and AST≤ 5×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula); They have not received radiotherapy, molecular targeted therapy, or surgery within 3 weeks before the start of the study, and have recovered from the acute toxicity of previous treatment (if surgery was performed, the wound has healed completely); No peripheral neuropathy or grade I peripheral neurotoxicity; ECOG score ≤1, and life expectancy ≥3 months; Fertile female subjects were required to use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug; Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: Radiotherapy (except for palliative causes), chemotherapy, and immunotherapy were used in the first 3 weeks of treatment, except bisphosphonate (which can be used for bone metastasis); Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol); A history of clinically important or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmia within the last 6 months; Persistent grade 1 or higher adverse reactions caused by previous treatments. The exception to this is hair loss or something the researchers don't think should be ruled out. Such cases should be clearly documented in the investigator's notes; Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment; Pregnant or lactating patients; Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years.

Sites / Locations

  • Fudan University Shanghai Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

IM/HER2-low

IM/HER2-0

BLIS / HER2-low

BLIS /HER2-0

LAR / HER2-low

LAR /HER2-0

MES/ HER2-low

MES /HER2-0

Arm Description

If patients were triple-negative breast cancer with IM subtype and HER2-low-positive

If patients were triple-negative breast cancer with IM subtype and HER2-zero

If patients were triple-negative breast cancer with BLIS subtype and HER2-low-positive

If patients were triple-negative breast cancer with BLIS subtype and HER2-zero

If patients were triple-negative breast cancer with LAR subtype and HER2-low-positive

If patients were triple-negative breast cancer with LAR subtype and HER2-zero

If patients were triple-negative breast cancer with MES subtype and HER2-low-positive

If patients were triple-negative breast cancer with MES subtype and HER2-zero

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

Secondary Outcome Measures

Progression Free Survival (PFS)
Time to progressive disease (according to RECIST1.1)
Duration of Response (DoR)
Duration of whose best outcome is complete remission or partial remission (according to RECIST1.1)
Disease Control Rate (DCR)
The proportion of patients with the best overall response of CR, PR, or stable disease (SD)
Overall Survival (OS)
Time to death due to any cause
CTCAE scale (V5.0)
To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V5.0)

Full Information

First Posted
February 19, 2023
Last Updated
February 19, 2023
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05749588
Brief Title
FUSCC Refractory TNBC Platform Study (FUTURE2.0)
Official Title
Precision Platform Study of Refractory Triple-negative Breast Cancer Based on Molecular Subtyping((A Phase II, Open-label, Single-center Platform Study)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 2023 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
June 2026 (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
No

5. Study Description

Brief Summary
This is a Phase II, open-label, Single-center platform study research based on molecular subtypes to explore precision therapy in refractory triple-negative breast cancer.
Detailed Description
This is a Phase II, open-label, Single-center platform study,Based on FUSCC four TNBC subtypes and the results of the previous FUTURE trial, the investigators designed this platform trial, which for combined the TNBC subtyping and genomic sequencing-guided precision targeted therapy for refractory metastatic TNBC patients. In this trial, refractory mTNBC patients eligible for inclusion can be divided into various precision treatment group according to molecular typing and subtyping to evaluate the efficacy and safety of multiple precision targeted treatment. The research therapy arm can be updated with the update of basic translational research in our center, especially the refinement of typing, the discovery of new targets and the development of novel targeted drugs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple-negative Breast Cancer
Keywords
TNBC, Molecular Subtype, Precision Treatment, Platform Study

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
IM/HER2-low
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with IM subtype and HER2-low-positive
Arm Title
IM/HER2-0
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with IM subtype and HER2-zero
Arm Title
BLIS / HER2-low
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with BLIS subtype and HER2-low-positive
Arm Title
BLIS /HER2-0
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with BLIS subtype and HER2-zero
Arm Title
LAR / HER2-low
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with LAR subtype and HER2-low-positive
Arm Title
LAR /HER2-0
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with LAR subtype and HER2-zero
Arm Title
MES/ HER2-low
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with MES subtype and HER2-low-positive
Arm Title
MES /HER2-0
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with MES subtype and HER2-zero
Intervention Type
Drug
Intervention Name(s)
A1: SHR-A1811
Intervention Description
A1: an anti-HER2 antibody-drug conjugate (ADC)
Intervention Type
Drug
Intervention Name(s)
A2: SHR-A1811 with Camrelizumab
Other Intervention Name(s)
SHR-1210
Intervention Description
A2: SHR-A1811: an anti-HER2 antibody-drug conjugate (ADC) Camrelizumab: an anti-programmed death-1 (PD-1) antibody
Intervention Type
Drug
Intervention Name(s)
B1: TROP2 ADC
Intervention Description
B1: an Trophoblast cell-surface antigen 2 (TROP2) ADC
Intervention Type
Drug
Intervention Name(s)
B2: TROP2 ADC with Camrelizumab
Other Intervention Name(s)
SHR-1210
Intervention Description
B2: TROP2 ADC : an Trophoblast cell-surface antigen 2 (TROP2) ADC Camrelizumab: an anti-programmed death-1 (PD-1) antibody
Intervention Type
Drug
Intervention Name(s)
C1: SHR-A1811
Intervention Description
C1: an anti-HER2 antibody-drug conjugate (ADC)
Intervention Type
Drug
Intervention Name(s)
C2: SHR-A1811 with BP102
Intervention Description
C2: SHR-A1811: an anti-HER2 antibody-drug conjugate (ADC) BP102: a humanized recombinant monoclonal IgG1 antibody (biosimilar to bevacizumab)
Intervention Type
Drug
Intervention Name(s)
D1: TROP2 ADC
Intervention Description
D1: an Trophoblast cell-surface antigen 2 (TROP2) ADC
Intervention Type
Drug
Intervention Name(s)
D2: TROP2 ADC with BP102
Intervention Description
D2: TROP2 ADC : an Trophoblast cell-surface antigen 2 (TROP2) ADC BP102: a humanized recombinant monoclonal IgG1 antibody (biosimilar to bevacizumab)
Intervention Type
Drug
Intervention Name(s)
E1: SHR-A1811
Intervention Description
E1: an anti-HER2 antibody-drug conjugate (ADC)
Intervention Type
Drug
Intervention Name(s)
F1: TROP2 ADC
Intervention Description
F1: an Trophoblast cell-surface antigen 2 (TROP2) ADC
Intervention Type
Drug
Intervention Name(s)
G1: SHR-A1811
Intervention Description
G1: an anti-HER2 antibody-drug conjugate (ADC)
Intervention Type
Drug
Intervention Name(s)
H1: TROP2 ADC
Intervention Description
H1: an Trophoblast cell-surface antigen 2 (TROP2) ADC
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)
Time Frame
Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study (approximately 3 years)
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
Time to progressive disease (according to RECIST1.1)
Time Frame
Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study (approximately 3 years)
Title
Duration of Response (DoR)
Description
Duration of whose best outcome is complete remission or partial remission (according to RECIST1.1)
Time Frame
Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study(approximately 3 years)
Title
Disease Control Rate (DCR)
Description
The proportion of patients with the best overall response of CR, PR, or stable disease (SD)
Time Frame
Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the completion of study(approximately 3 years)
Title
Overall Survival (OS)
Description
Time to death due to any cause
Time Frame
Randomization to death from any cause, through the end of study (approximately 3 years)
Title
CTCAE scale (V5.0)
Description
To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V5.0)
Time Frame
Up to One Year during follow-up

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female aged ≥18 years; TNBC invasive breast cancer confirmed by histology (specific definition: ER <1% positive tumor cells by immunohistochemistry is defined as ER negative, PR <1% positive tumor cells is defined as PR negative, HER2 0-1+ or HER2 ++ but negative by FISH without amplification was defined as HER2 negative); Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer; Progression after at least two prior therapeutic regimens for advanced/metastatic TNBC At least one measurable lesion according to RECIST 1.1 (conventional CT scan ≥20 mm, spiral CT scan ≥10 mm, measurable lesion has not received radiotherapy); The functions of the main organs are basically normal and meet the following conditions: i. Blood routine examination criteria shall meet: HB ≥90 g/L (no blood transfusion within 14 days); The ANC acuity 1.5 x 109 / L; PLT acuity 75 x 109 / L; ii. Biochemical tests should meet the following criteria: TBIL ≤1.5×ULN (upper limit of normal value); ALT and AST ≤3×ULN; If liver metastases were present, ALT and AST≤ 5×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula); They have not received radiotherapy, molecular targeted therapy, or surgery within 3 weeks before the start of the study, and have recovered from the acute toxicity of previous treatment (if surgery was performed, the wound has healed completely); No peripheral neuropathy or grade I peripheral neurotoxicity; ECOG score ≤1, and life expectancy ≥3 months; Fertile female subjects were required to use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug; Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: Radiotherapy (except for palliative causes), chemotherapy, and immunotherapy were used in the first 3 weeks of treatment, except bisphosphonate (which can be used for bone metastasis); Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol); A history of clinically important or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmia within the last 6 months; Persistent grade 1 or higher adverse reactions caused by previous treatments. The exception to this is hair loss or something the researchers don't think should be ruled out. Such cases should be clearly documented in the investigator's notes; Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment; Pregnant or lactating patients; Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhimin Shao, M.D.
Phone
+86-021-64175590
Ext
88807
Email
zhimingshao@yahoo.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yin Liu, M.D.
Phone
+86-021-64175590
Ext
88603
Email
liuyinfudan@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhimin Shao, M.D.
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
ZIP/Postal Code
200032
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

FUSCC Refractory TNBC Platform Study (FUTURE2.0)

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