Breast CancerPhase 2BCTOP-L-M01NCT05949541
Efficacy of Everolimus Combined With First-line Endocrine Therapy for HR+/HER2- SNF1-subtype Advanced Breast Cancer
A Phase 2 study testing Everolimus 10 mg, CDK4/6 Inhibitor SHR6390 and Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors in people with Breast Cancer and Advanced Breast Cancer, run by Fudan University at 1 site in China.
Trial summary
This is a randomized, controlled, open-label, phase II study to explore the efficacy and safety of Everolimus in combination with standard first-line endocrine therapy for the HR+/ HER2-SNF1 subtype of advanced breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Breast Cancer, Advanced Breast Cancer
- What is being tested?
- Everolimus 10 mg, CDK4/6 Inhibitor SHR6390 and Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 265 participants
- Where
- 1 siteChina
- Study dates
- 26 Jul 2023to Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients need to meet all of the following conditions
- Patients must be ≥18 and ≤ 75 years of age;
- Pathologically confirmed breast cancer is HR+/HER2- breast cancer (IHC ER >10%, or/and PR>10%, HER 0 OR +, if HER2++, FISH negative);
- SNF1 subtype definition: SNF1 subtype confirmed by digital pathology of H\&E sections;
- Locally advanced breast cancer (radical local therapy is not possible) or metastatic breast cancer (without using adjuvant CDK4/6 inhibitors in the past, or one year after adjuvant CDK4/6 inhibitor therapy has ended);
- No prior therapy (chemotherapy, targeted therapy, etc.) for advanced or metastatic breast cancer;
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- Patients with at least one measurable lesion that has not previously received radiation therapy 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×ULN (upper limit of normal value); ALT and AST≤3 x ULN; In case of liver metastasis, ALT and AST≤5×ULN; Serum Cr ≤1.5×ULN, endogenous creatinine clearance > 50ml/min (Cockcroft-Gault formula);
- ECOG performance status 0 or 1; The expected survival is more than 3 months;
- Fertile female is 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.
Who cannot join
- Patients with any of the following conditions were excluded from the study
- Patients with central nervous system metastasis out of control (symptoms need to use glucocorticoids or mannitol).
- 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;
- Radiotherapy, chemotherapy, surgery, other targeted therapy and immunotherapy for advanced HR+/HER2- breast cancer within 4 weeks prior to first administration of drugs used in this study.
- Pregnant or lactating patients;
- Other malignancies within the previous 3 years, excluding cured skin basal cell carcinoma and cervical carcinoma in situ;
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- Significant comorbid medical conditions, including mental illnesses that the investigator or sponsor believes would adversely affect the patient's participation in the study;
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Zhimin Shao Shao, MD,PhD, 86-021-64175590, zhimingshao@yahoo.com
About this study
Official title: Study of Efficacy of Everolimus Combined With First-line Endocrine Therapy for HR+/HER2- (Open, Randomized, Phase II )
This is a randomized, controlled, open-label, phase II study to explore the efficacy and safety of Everolimus in combination with standard first-line endocrine therapy for the HR+/ HER2-SNF1 subtype of advanced breast cancer. The study was used to explore the efficacy of Everolimus in combination with standard endocrine therapy.
Read the detailed description
A total of 584 patients with luminal breast cancer who received surgery in the breast surgery Department of the Affiliated Cancer Hospital of Fudan University were collected in the early stage. All patients could be divided into four categories, namely SNF1 (classical luminal type), SNF2 (immune-mediated type), SNF1 (proliferative type), and SNF4 (receptor tyrosine kinase-driven type), through clustering by the SNF algorithm. SNF1 (classical luminal type): The transcriptional component type is dominated by PAM50 LumA, with high PIK3CA mutation and low TP53 mutation. By combining artificial intelligence based on H\&E pathological sections with deep learning methodology, molecular typing can be effectively distinguished. Prior to enrollment, the patient's primary lesion or metastasis was classified by molecular classification based on the H\&E section combined with digital pathology, and SNF1 was confirmed to be considered for subsequent enrollment.
Receivers will be randomly assigned 1:1 to either Everolimus plus Standard Endocrine therapy (study group) or Standard Endocrine therapy (control group).
Treatment will continue until disease progression, intolerable toxicity, informed withdrawal, or death from any cause.
- Conditions
- Breast Cancer, Advanced Breast Cancer
- Being tested
- Everolimus 10 mg, CDK4/6 Inhibitor SHR6390, Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors
- Keywords
- luminal breast cancer, advanced breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus 10 mgDrug
Also called Afinitor
Everolimus is a kind of mTOR inhibitor which has been approved to use in several kinds of cancers, especially in metastatic breast cancer.
CDK4/6 Inhibitor SHR6390Drug
Also called Dalpiciclib
Dalpiciclib (SHR6390) is a kind of CDK4/6 inhibitor that has demonstrated tolerability and preliminary clinical activity in patients with heavily pretreated hormone receptor-positive, HER2-negative advanced breast cancer.
Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitorsDrug
Also called Endocrine therapy
Endocrine therapy combined with CDK4/6 inhibitors is the standard first-line therapy for advanced luminal breast cancer. Investigators choose endocrine therapy including Letrozole, Anastrozole, Exemestane, and Fulvestrant. Postmenopausal participants should use Goserelin.
| Study group | Role | What they receive |
|---|---|---|
| Arm-A | Experimental | Everolimus + CDK4/6 inhibitor+ Endocrine therapy group:
Everolimus, 10mg po. qd; Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle.
Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks. Receives: Drug: Everolimus 10 mg; Drug: CDK4/6 Inhibitor SHR6390; Drug: Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors |
| Arm-B | Active comparator | CDK4/6 inhibitor+ Endocrine therapy group:
Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle.
Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks. Receives: Drug: CDK4/6 Inhibitor SHR6390; Drug: Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 5 years
Secondary outcomes (4)
Clinical Benefit Rate (CBR)
CBR is the total percentage of participants who achieved a complete response, partial response, or had stable disease for 6 months or more.
Measured: Approximately 5 years
Objective Response Rate (ORR)
ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR) based on BICR and investigator assessment using RECIST 1.1.
Measured: Approximately 5 years
Overall Survival (OS)
OS is defined as the time from randomisation until the date of death due to any cause.
Measured: Approximately 5 years
Safety and tolerability
Number of adverse events according to NCI-CTCAE Version 5.0 per each treatment arm.
Measured: Approximately 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2023
- Study start26 Jul 2023
- Primary completionJul 2026 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 265 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhimin Shao, Fudan University
- Investigators
- Zhimin Shao, MD,PhD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05949541
- Sponsor's protocol ID
- SCHBCC-N062
- Acronym
- BCTOP-L-M01
- Status last verified
- Feb 2024
- First submitted
- 9 Jul 2023
- Last updated
- 8 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Efficacy of Everolimus Combined With First-line Endocrine Therapy for HR+/HER2- (Open, Randomized, Phase II )
- ClinicalTrials.gov ID
- NCT05949541
- Acronym / sponsor ID
- BCTOP-L-M01 / SCHBCC-N062
- Conditions
- Breast Cancer, Advanced Breast Cancer
- Keywords
- luminal breast cancer, advanced breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 265 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 26 Jul 2023 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 18 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, controlled, open-label, phase II study to explore the efficacy and safety of Everolimus in combination with standard first-line endocrine therapy for the HR+/ HER2-SNF1 subtype of advanced breast cancer. The study was used to explore the efficacy of Everolimus in combination with standard endocrine therapy.
Detailed description
A total of 584 patients with luminal breast cancer who received surgery in the breast surgery Department of the Affiliated Cancer Hospital of Fudan University were collected in the early stage. All patients could be divided into four categories, namely SNF1 (classical luminal type), SNF2 (immune-mediated type), SNF1 (proliferative type), and SNF4 (receptor tyrosine kinase-driven type), through clustering by the SNF algorithm. SNF1 (classical luminal type): The transcriptional component type is dominated by PAM50 LumA, with high PIK3CA mutation and low TP53 mutation. By combining artificial intelligence based on H\&E pathological sections with deep learning methodology, molecular typing can be effectively distinguished. Prior to enrollment, the patient's primary lesion or metastasis was classified by molecular classification based on the H\&E section combined with digital pathology, and SNF1 was confirmed to be considered for subsequent enrollment.
Receivers will be randomly assigned 1:1 to either Everolimus plus Standard Endocrine therapy (study group) or Standard Endocrine therapy (control group).
Treatment will continue until disease progression, intolerable toxicity, informed withdrawal, or death from any cause.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm-A | Experimental | Drug: Everolimus 10 mg, Drug: CDK4/6 Inhibitor SHR6390, Drug: Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitorsEverolimus + CDK4/6 inhibitor+ Endocrine therapy group: Everolimus, 10mg po. qd; Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks. |
| Arm-B | Active comparator | Drug: CDK4/6 Inhibitor SHR6390, Drug: Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitorsCDK4/6 inhibitor+ Endocrine therapy group: Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients need to meet all of the following conditions
Key exclusion criteria (9 listed)
- Patients with any of the following conditions were excluded from the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus 10 mgAlso: AfinitorEverolimus is a kind of mTOR inhibitor which has been approved to use in several kinds of cancers, especially in metastatic breast cancer. | Drug | Arm-A |
| CDK4/6 Inhibitor SHR6390Also: DalpiciclibDalpiciclib (SHR6390) is a kind of CDK4/6 inhibitor that has demonstrated tolerability and preliminary clinical activity in patients with heavily pretreated hormone receptor-positive, HER2-negative advanced breast cancer. | Drug | Arm-A, Arm-B |
| Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitorsAlso: Endocrine therapyEndocrine therapy combined with CDK4/6 inhibitors is the standard first-line therapy for advanced luminal breast cancer. Investigators choose endocrine therapy including Letrozole, Anastrozole, Exemestane, and Fulvestrant. Postmenopausal participants should use Goserelin. | Drug | Arm-A, Arm-B |
Primary outcome
Progression Free Survival (PFS)
Time frame: Approximately 5 years
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.
4 secondary outcomes
Clinical Benefit Rate (CBR)
Time frame: Approximately 5 years
Objective Response Rate (ORR)
Time frame: Approximately 5 years
Overall Survival (OS)
Time frame: Approximately 5 years
Safety and tolerability
Time frame: Approximately 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zhimin Shao, MD,PhD principal investigator
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus 10 mg, CDK4/6 Inhibitor SHR6390 and Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors in people with Breast Cancer and Advanced Breast Cancer, run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhimin Shao, MD, PhD (+86-021-64175590 ext. 88807, zhimingshao@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: Approximately 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2024.