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Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy (FASCINATE-N)

Primary Purpose

Breast Neoplasm, Breast Cancer, Breast Tumors

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Dalpiciclib
Pyrotinib
SHR-A1811
SHR-1316
Camrelizumab
Trophoblast cell-surface antigen 2 (TROP2) ADC
Pertuzumab
Trastuzumab
Goserelin
Letrozole
Nab paclitaxel
Carboplatin
Epirubicin
Cyclophosphamide
Fluzoparib
HER2 ADC
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Neoplasm

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically confirmed invasive cancer of the breast and meet the clinical stage T2-4, N1-3, M0 criteria;
  • Age between18-70 years;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
  • ER, PR and HER2 status were measured by immunohistochemistry (IHC);
  • LVEF≥55%；
  • Definition of SNF subtypes: SNF subtypes confirmed by digital pathology of H&E slices;
  • Triple negative subtyping: On the basis of triple-negative pathological diagnosis, AR, cluster of differentiation 8 (CD8) and Forkhead Box C1 (FOXC1) were combined to define the subtyping;
  • At least one measurable lesion according to RECIST version 1.1
  • Normal organ and marrow function: Hemoglobin (HB) ≥90 g/L (No blood was transfused within 14 days), Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 75,000/μL, Total bilirubin ≤ 1.5 x ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3 x ULN, creatinine < 1 x ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);
  • Non-pregnant and non-lactating, fertile female subjects were required to use a medically approved contraceptive method for the duration of the study treatment and at least 3 months after the last use of the study drug;
  • Ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

  • Previous cytotoxic chemotherapy, endocrine therapy, biological therapy or radiotherapy for any reason;
  • Patients with New York Heart Association (NYHA) grade II or above heart disease (including grade II);
  • Patients with severe systemic infections or other serious diseases;
  • Patients with known allergy or intolerance to the study drug or its excipients;
  • Other malignant tumors in the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer;
  • Pregnant or lactating patients of childbearing age who refused to take appropriate contraceptive measures during the course of the study;
  • Participated in other trial studies within 30 days before the administration of the first dose of the study drug;
  • Patients who were judged by the investigator to be unsuitable for this study.

Sites / Locations

  • Fudan University Shanghai Cancer Center Shanghai, China, 200032Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm 17

Arm 18

Arm 19

Arm 20

Arm 21

Arm 22

Arm 23

Arm 24

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

L1-1

L1-2

L2-1

L2-2

L3-1

L3-2

L4-1

L4-2

L4-low-1

L4-low-2

TN1-1

TN1-2

TN2-1

TN2-2

TN3-1

TN3-2

TN4-1

TN4-2

TN5-1

TN5-2

H1-1

H1-2

H2-1

H2-2

Arm Description

If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype

If patients were HR+HER2- with SNF1 subtype

If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype

If patients were HR+HER2- with SNF2 subtype

If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype

If patients were HR+HER2- with SNF3 subtype

If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype

If patients were HR+HER2- with SNF4 subtype

If patients were HR+HER2-low with SNF4 subtype

If patients were HR+HER2-low with SNF4 subtype

If patients were triple-negative breast cancer with immunomodulatory (IM) subtype

If patients were triple-negative breast cancer with IM subtype

If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype

If patients were triple-negative breast cancer with BLIS subtype

If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype

If patients were triple-negative breast cancer with AR HER2 subtype

If patients were HR-HER2-low

If patients were HR-HER2-low

If patients were triple-negative breast cancer with other subtypes

If patients were triple-negative breast cancer with other subtypes

If patients were HR+HER2+

If patients were HR+HER2+

If patients were HR-HER2+

If patients were HR-HER2+

Outcomes

Primary Outcome Measures

Pathological complete response rate (pCR)
Pathological complete response rate

Secondary Outcome Measures

invasive disease-free survival (iDFS)
To determine three-year invasive disease-free survival (iDFS) among the treatment arms
Overall response rate (ORR)
Complete response (CR) + partial response (PR)
CTCAE scale (V4.0)
4) To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V4.0)
Evaluate gene expression profile during treatment
To measure gene expression profile of baseline and sequential tumor samples during treatment, through RNA-seq platform
Number of peripheral blood mononuclear cells (PBMC) count during treatment
To measure number of peripheral blood mononuclear cells (PBMC) count from baseline and sequential blood samples during treatment, through Flow CytoMetry platform

Full Information

First Posted
September 25, 2022
Last Updated
February 6, 2023
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05582499
Brief Title
Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy
Acronym
FASCINATE-N
Official Title
Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy (FASCINATE-N)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2025 (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
The purpose of this study is to establish a prospective, single-center platform research based on clinical subtypes to explore precision neoadjuvant therapy in patients with operable breast cancer who met the indications for neoadjuvant chemotherapy and by the update of basic translational research in the center, especially the refinement of typing, the discovery of new targets and the development of novel targeted drugs, verified the effectiveness of new targeted drugs in neoadjuvant therapy.
Detailed Description
FASCINATE-N is a platform that will compare the efficacy of novel drugs alone or in combination with standard chemotherapy with the efficacy of standard therapy alone. The goal is to identify improved treatment regimens for subsets on the basis of clinical subtyping. In this trial, breast cancer patients eligible for inclusion can be randomly divided into the precision treatment group and conventional neoadjuvant chemotherapy group according to molecular typing and subtyping. 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. As described for previous adaptive trials, regimens that show to be more effective than standard therapy will graduate from the trial with their corresponding biomarker signature(s). Regimens will be dropped if they show a low probability of improved efficacy with any biomarker signature. New drugs will enter as those that have undergone testing complete their evaluation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasm, Breast Cancer, Breast Tumors, Triple-Negative Breast Cancer (TNBC), HER2-positive Breast Cancer, HER2-negative Breast Cancer, Hormone Receptor Positive Tumor, Hormone Receptor Negative Tumor, Early-stage Breast Cancer, Locally Advanced Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
716 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
L1-1
Arm Type
Experimental
Arm Description
If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype
Arm Title
L1-2
Arm Type
Active Comparator
Arm Description
If patients were HR+HER2- with SNF1 subtype
Arm Title
L2-1
Arm Type
Experimental
Arm Description
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
Arm Title
L2-2
Arm Type
Active Comparator
Arm Description
If patients were HR+HER2- with SNF2 subtype
Arm Title
L3-1
Arm Type
Experimental
Arm Description
If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype
Arm Title
L3-2
Arm Type
Active Comparator
Arm Description
If patients were HR+HER2- with SNF3 subtype
Arm Title
L4-1
Arm Type
Experimental
Arm Description
If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype
Arm Title
L4-2
Arm Type
Active Comparator
Arm Description
If patients were HR+HER2- with SNF4 subtype
Arm Title
L4-low-1
Arm Type
Experimental
Arm Description
If patients were HR+HER2-low with SNF4 subtype
Arm Title
L4-low-2
Arm Type
Active Comparator
Arm Description
If patients were HR+HER2-low with SNF4 subtype
Arm Title
TN1-1
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with immunomodulatory (IM) subtype
Arm Title
TN1-2
Arm Type
Active Comparator
Arm Description
If patients were triple-negative breast cancer with IM subtype
Arm Title
TN2-1
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype
Arm Title
TN2-2
Arm Type
Active Comparator
Arm Description
If patients were triple-negative breast cancer with BLIS subtype
Arm Title
TN3-1
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype
Arm Title
TN3-2
Arm Type
Active Comparator
Arm Description
If patients were triple-negative breast cancer with AR HER2 subtype
Arm Title
TN4-1
Arm Type
Experimental
Arm Description
If patients were HR-HER2-low
Arm Title
TN4-2
Arm Type
Active Comparator
Arm Description
If patients were HR-HER2-low
Arm Title
TN5-1
Arm Type
Experimental
Arm Description
If patients were triple-negative breast cancer with other subtypes
Arm Title
TN5-2
Arm Type
Active Comparator
Arm Description
If patients were triple-negative breast cancer with other subtypes
Arm Title
H1-1
Arm Type
Experimental
Arm Description
If patients were HR+HER2+
Arm Title
H1-2
Arm Type
Active Comparator
Arm Description
If patients were HR+HER2+
Arm Title
H2-1
Arm Type
Experimental
Arm Description
If patients were HR-HER2+
Arm Title
H2-2
Arm Type
Active Comparator
Arm Description
If patients were HR-HER2+
Intervention Type
Drug
Intervention Name(s)
Dalpiciclib
Other Intervention Name(s)
SHR-6390
Intervention Description
an oral cyclin-dependent kinases (CDK) 4/6 inhibitor
Intervention Type
Drug
Intervention Name(s)
Pyrotinib
Intervention Description
an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor
Intervention Type
Drug
Intervention Name(s)
SHR-A1811
Intervention Description
an anti-HER2 antibody-drug conjugate (ADC)
Intervention Type
Drug
Intervention Name(s)
SHR-1316
Intervention Description
an anti-programmed death ligand 1 (PD-L1) antibody
Intervention Type
Drug
Intervention Name(s)
Camrelizumab
Other Intervention Name(s)
SHR-1210
Intervention Description
an anti-programmed death-1 (PD1) antibody
Intervention Type
Drug
Intervention Name(s)
Trophoblast cell-surface antigen 2 (TROP2) ADC
Intervention Description
anti-TROP2 ADC
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Intervention Description
Pertuzumab
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Intervention Description
Trastuzumab
Intervention Type
Drug
Intervention Name(s)
Goserelin
Intervention Description
goserelin
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
letrozole
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
Albumin paclitaxel
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Intervention Description
Epirubicin
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
Fluzoparib
Other Intervention Name(s)
SHR-3162
Intervention Description
an original poly adenosine diphosphate-ribose polymerase (PARP) inhibitor
Intervention Type
Drug
Intervention Name(s)
HER2 ADC
Intervention Description
anti-HER2 ADC
Primary Outcome Measure Information:
Title
Pathological complete response rate (pCR)
Description
Pathological complete response rate
Time Frame
through study completion, up to 24 weeks
Secondary Outcome Measure Information:
Title
invasive disease-free survival (iDFS)
Description
To determine three-year invasive disease-free survival (iDFS) among the treatment arms
Time Frame
Three-year Post-surgery Follow-up
Title
Overall response rate (ORR)
Description
Complete response (CR) + partial response (PR)
Time Frame
up to 24 weeks
Title
CTCAE scale (V4.0)
Description
4) To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V4.0)
Time Frame
through study completion, an average of 1 year
Title
Evaluate gene expression profile during treatment
Description
To measure gene expression profile of baseline and sequential tumor samples during treatment, through RNA-seq platform
Time Frame
through study completion, up to 24 weeks
Title
Number of peripheral blood mononuclear cells (PBMC) count during treatment
Description
To measure number of peripheral blood mononuclear cells (PBMC) count from baseline and sequential blood samples during treatment, through Flow CytoMetry platform
Time Frame
through study completion, up to 24 weeks

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: Histologically confirmed invasive cancer of the breast and meet the clinical stage T2-4, N1-3, M0 criteria; Age between18-70 years; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; ER, PR and HER2 status were measured by immunohistochemistry (IHC); LVEF≥55%； Definition of SNF subtypes: SNF subtypes confirmed by digital pathology of H&E slices; Triple negative subtyping: On the basis of triple-negative pathological diagnosis, AR, cluster of differentiation 8 (CD8) and Forkhead Box C1 (FOXC1) were combined to define the subtyping; At least one measurable lesion according to RECIST version 1.1 Normal organ and marrow function: Hemoglobin (HB) ≥90 g/L (No blood was transfused within 14 days), Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 75,000/μL, Total bilirubin ≤ 1.5 x ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3 x ULN, creatinine < 1 x ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula); Non-pregnant and non-lactating, fertile female subjects were required to use a medically approved contraceptive method for the duration of the study treatment and at least 3 months after the last use of the study drug; Ability to understand and willingness to sign a written informed consent Exclusion Criteria: Previous cytotoxic chemotherapy, endocrine therapy, biological therapy or radiotherapy for any reason; Patients with New York Heart Association (NYHA) grade II or above heart disease (including grade II); Patients with severe systemic infections or other serious diseases; Patients with known allergy or intolerance to the study drug or its excipients; Other malignant tumors in the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer; Pregnant or lactating patients of childbearing age who refused to take appropriate contraceptive measures during the course of the study; Participated in other trial studies within 30 days before the administration of the first dose of the study drug; Patients who were judged by the investigator to be unsuitable for this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhimin Shao, Professor
Phone
+86(021)64175590
Email
zhimingshao@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhimin Shao, Professor
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center Shanghai, China, 200032
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhimin Shao, M.D.
Phone
+86-021-64175590
Ext
88807
Email
zhimingshao@yahoo.com
First Name & Middle Initial & Last Name & Degree
Min He, M.D
Phone
+86-021-64175590
Ext
88603
Email
minsmiler@126.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy

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