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Everolimus With Investigator's Choice of Chemotherapy in Advanced Triple-Negative Breast Cancer (TNBC) With Luminal Androgen Receptor (LAR) Subtype

Primary Purpose

Triple Negative Breast Cancer, Metastatic Breast Cancer, Mutation

Status
Not yet recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Everolimus
Investigator's Choice of Chemotherapy
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 triple negative breast cancer, metastatic breast cancer, PI3K/AKT/mTOR mutation

Eligibility Criteria

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

Inclusion Criteria: Patients need to meet all of the following conditions Patients must be ≥18 and ≤ 70 years of age; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; The expected survival is more than 3 months; Pathologically confirmed breast cancer is triple negative breast cancer (IHC ER < 1%, PR<1%, HER2 0 OR +, if HER2++, FISH negative), and LAR subtype with mutation in PAM pathway; Recurrent or metastatic breast cancer; Patients with local recurrence need to be confirmed by the investigator that radical surgical resection is not possible;. No prior therapy (chemotherapy, targeted therapy, etc.) for advanced or metastatic breast cancer; Patients with at least one lesion (measurable and/or unmeasurable) that has not previously received radiation therapy can be accurately evaluated by CT/MRI at baseline and can be evaluated repeatedly according to RECIST 1.1; The functions of the main organs are basically normal, and the following conditions are met: Blood routine examination standards should meet: HB≥90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L; PLT≥75×109/L; Biochemical examination shall meet the following standards: TBIL≤1.5× upper limit of normal value(ULN); alanine aminotransferase (ALT) and AST≤3 x ULN; In case of liver metastasis, ALT and AST≤5×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance > 50ml/min (Cockcroft-Gault formula); Patients have not received radiotherapy, endocrine therapy, molecular targeted therapy, or surgery within 3 weeks prior to study initiation, and have recovered from acute toxic effects of prior treatment (if surgery is present, the wound has fully healed); No peripheral neuropathy or grade I peripheral neurotoxicity; Fertile female are required to use a medically approved contraceptive during study treatment and for at least 3 months after the last use of the study drug; Patients voluntarily join the study, sign the informed consent, have good compliance, and cooperate with follow-up. Exclusion Criteria: Patients with any of the following conditions were excluded from the study: Patients with known central nervous system metastasis or history of central nervous system metastasis prior to screening. For patients with clinically suspected central nervous system metastasis, enhanced CT or enhanced MRI must be performed within 28 days before the first dose to rule out central nervous system metastasis. A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia; Persistent grade ≥1 adverse events due to previous treatment. The exception to this is hair loss or something the researchers believe should not be ruled out. Such cases should be clearly documented in the investigator's notes; Major surgery was performed within 3 weeks of the first course of trial treatment (except for minor outpatient surgery, such as placement of vascular access); Pregnant or lactating patients; Other malignancies within the previous 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or skin squamous cell carcinoma; Inability to swallow, chronic diarrhea and intestinal obstruction, there are many factors affecting drug use and absorption; There is a third space effusion that cannot be controlled by drainage or other methods (such as excessive pleural fluid and ascites); Participated in other anti-tumor drug clinical trials within 4 weeks before taking the study drug for the first time; Long-term unhealed wounds or incomplete healing fractures; Patients with known Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection active phase or hepatitis B DNA≥500, or chronic phase with abnormal liver function; Allergic physique, or known allergic history of the drug components of this program; Or allergic to other monoclonal antibodies; The investigator does not consider the patient suitable for participation in any other circumstances of the study.

Sites / Locations

  • Fudan University Shanghai Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Everolimus plus Investigator's Choice of Chemotherapy

Investigator's Choice of Chemotherapy

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)
The interval from randomization until the first occurrence of disease progression (according to RECIST 1.1) or death from any cause, which ever occurs first.

Secondary Outcome Measures

Objective response rate (ORR)
The proportion of participants who have a complete response (CR) or partial response (PR) according to RECIST 1.1.
Duration of response (DoR)
The interval from date of first detection of objective response until the first occurrence of disease progression (according to RECIST 1.1) or death from any cause, which ever occurs first.
Disease control rate (DCR)
The proportion of participants with complete response, partial response, and stable disease for more than 4 weeks in which response can be evaluated.
Overall survival (OS)
The interval from randomization until the date of death due to any cause.
Safety and tolerability
Number of adverse events according to NCI-CTCAE Version 5.0 per each treatment arm
Number of participants with patient reported outcome (PRO)
A report directly from a patient about his or her health and the outcome of treatment.

Full Information

First Posted
July 13, 2023
Last Updated
July 25, 2023
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05954442
Brief Title
Everolimus With Investigator's Choice of Chemotherapy in Advanced Triple-Negative Breast Cancer (TNBC) With Luminal Androgen Receptor (LAR) Subtype
Official Title
An Open, Randomized Phase III Study of Everolimus With Investigator's Choice of Chemotherapy Versus Chemotherapy in The First-Line Treatment of Luminal Androgen Receptor (LAR) Subtype With PI3K/AKT/mTOR Pathway Mutation of Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (FUSCC-TNBC-LAR)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 2023 (Anticipated)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 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

5. Study Description

Brief Summary
The goal of this clinical trial is to evaluate the efficacy of investigator's choice of chemotherapy, either alone or in combination with everolimus, in treating patients with locally recurrent inoperable or metastatic triple-negative breast cancer, luminal androgen receptor (LAR) subtype with PI3K/AKT/mTOR (PAM) pathway mutation, as the first-line treatment.
Detailed Description
Eligible participants will be those diagnosed with estrogen receptor (ER)-negative [Immunohistochemistry (IHC) ER positive <1% ) , progesterone receptor (PR) negative(IHC PR positive <1% ) , and human epidermal growth factor receptor 2 (HER2)-negative [IHC 0 or +; or IHC ++, Fluorescence in situ hybridization (FISH) -], LAR subtype with PAM pathway mutation locally recurrent inoperable or metastatic breast cancer, who have received no prior chemotherapy, targeted therapy or other treatments. The study is aimed to evaluate the efficacy of investigator's choice (ICC) of chemotherapy (nab-paclitaxel, capecitabine, eribulin, carboplatin, vinorelbine, or utidelone) either alone or in combination with everolimus. This study aims to see if everolimus plus chemotherapy allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving investigator's choice of chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Cancer, Metastatic Breast Cancer, Mutation
Keywords
triple negative breast cancer, metastatic breast cancer, PI3K/AKT/mTOR mutation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
203 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Everolimus plus Investigator's Choice of Chemotherapy
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Investigator's Choice of Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Afinitor
Intervention Description
Everolimus is a kind of mTOR inhibitors which has been approved to use in several kinds of cancers, especially in metastatic breast cancer .
Intervention Type
Drug
Intervention Name(s)
Investigator's Choice of Chemotherapy
Other Intervention Name(s)
ICC
Intervention Description
Investigator's choice of chemotherapy means the chemotherapy chosen by investigators/doctors to treat metastatic triple negative breast cancer, including nab-paclitaxel, capecitabine, eribulin, carboplatin, vinorelbine, or utidelone.
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
The interval from randomization until the first occurrence of disease progression (according to RECIST 1.1) or death from any cause, which ever occurs first.
Time Frame
Approximately 3 years
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
The proportion of participants who have a complete response (CR) or partial response (PR) according to RECIST 1.1.
Time Frame
Approximately 3 years
Title
Duration of response (DoR)
Description
The interval from date of first detection of objective response until the first occurrence of disease progression (according to RECIST 1.1) or death from any cause, which ever occurs first.
Time Frame
Approximately 3 years
Title
Disease control rate (DCR)
Description
The proportion of participants with complete response, partial response, and stable disease for more than 4 weeks in which response can be evaluated.
Time Frame
Approximately 3 years
Title
Overall survival (OS)
Description
The interval from randomization until the date of death due to any cause.
Time Frame
Approximately 3 years
Title
Safety and tolerability
Description
Number of adverse events according to NCI-CTCAE Version 5.0 per each treatment arm
Time Frame
Approximately 3 years
Title
Number of participants with patient reported outcome (PRO)
Description
A report directly from a patient about his or her health and the outcome of 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: Patients need to meet all of the following conditions Patients must be ≥18 and ≤ 70 years of age; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; The expected survival is more than 3 months; Pathologically confirmed breast cancer is triple negative breast cancer (IHC ER < 1%, PR<1%, HER2 0 OR +, if HER2++, FISH negative), and LAR subtype with mutation in PAM pathway; Recurrent or metastatic breast cancer; Patients with local recurrence need to be confirmed by the investigator that radical surgical resection is not possible;. No prior therapy (chemotherapy, targeted therapy, etc.) for advanced or metastatic breast cancer; Patients with at least one lesion (measurable and/or unmeasurable) that has not previously received radiation therapy can be accurately evaluated by CT/MRI at baseline and can be evaluated repeatedly according to RECIST 1.1; The functions of the main organs are basically normal, and the following conditions are met: Blood routine examination standards should meet: HB≥90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L; PLT≥75×109/L; Biochemical examination shall meet the following standards: TBIL≤1.5× upper limit of normal value(ULN); alanine aminotransferase (ALT) and AST≤3 x ULN; In case of liver metastasis, ALT and AST≤5×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance > 50ml/min (Cockcroft-Gault formula); Patients have not received radiotherapy, endocrine therapy, molecular targeted therapy, or surgery within 3 weeks prior to study initiation, and have recovered from acute toxic effects of prior treatment (if surgery is present, the wound has fully healed); No peripheral neuropathy or grade I peripheral neurotoxicity; Fertile female are required to use a medically approved contraceptive during study treatment and for at least 3 months after the last use of the study drug; Patients voluntarily join the study, sign the informed consent, have good compliance, and cooperate with follow-up. Exclusion Criteria: Patients with any of the following conditions were excluded from the study: Patients with known central nervous system metastasis or history of central nervous system metastasis prior to screening. For patients with clinically suspected central nervous system metastasis, enhanced CT or enhanced MRI must be performed within 28 days before the first dose to rule out central nervous system metastasis. A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia; Persistent grade ≥1 adverse events due to previous treatment. The exception to this is hair loss or something the researchers believe should not be ruled out. Such cases should be clearly documented in the investigator's notes; Major surgery was performed within 3 weeks of the first course of trial treatment (except for minor outpatient surgery, such as placement of vascular access); Pregnant or lactating patients; Other malignancies within the previous 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or skin squamous cell carcinoma; Inability to swallow, chronic diarrhea and intestinal obstruction, there are many factors affecting drug use and absorption; There is a third space effusion that cannot be controlled by drainage or other methods (such as excessive pleural fluid and ascites); Participated in other anti-tumor drug clinical trials within 4 weeks before taking the study drug for the first time; Long-term unhealed wounds or incomplete healing fractures; Patients with known Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection active phase or hepatitis B DNA≥500, or chronic phase with abnormal liver function; Allergic physique, or known allergic history of the drug components of this program; Or allergic to other monoclonal antibodies; The investigator does not consider the patient suitable for participation in any other circumstances of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhimin Shao, MD, PhD
Phone
+86-021-64175590
Ext
88807
Email
zhimingshao@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhimin Shao, MD, PhD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhimin Shao, M.D., Ph.D.
Phone
86-021-64175590
Email
zhimingshao@yahoo.com

12. IPD Sharing Statement

Learn more about this trial

Everolimus With Investigator's Choice of Chemotherapy in Advanced Triple-Negative Breast Cancer (TNBC) With Luminal Androgen Receptor (LAR) Subtype

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