Clinical trial NCT06929325: Sirolimus for Injection (Albumin-bound) Combined With Fulvestrant for HR+/HER2- Advanced/Metastatic Breast Cancer Patients Previously Treated With CDK4/6 Inhibitors
Official title: A Randomized, Double-blind, Multicenter Phase III Clinical Study to Evaluate the Efficacy and Safety of Sirolimus for Injection (Albumin-bound) Combined With Fulvestrant Versus Placebo Combined With Fulvestrant in HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer Patients After Prior CDK4/6 Inhibitor Treatment.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: HR+/HER2- Advanced/Metastatic Breast Cancer
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-04-16
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized, double-blind, multicenter phase III clinical study to evaluate the efficacy and safety of sirolimus for injection (albumin-bound) combined with fulvestrant in patients with HR+ and HER2- advanced breast cancer.


Eligibility criteria: Inclusion Criteria:

* 1. Aged 18 or above, regardless of gender; female patients must be postmenopausal, or premenopausal/perimenopausal.
* 2. Pathologically confirmed HR+, HER2- breast cancer.
* 3. Locally advanced or metastatic breast cancer, not suitable for curative surgery or radiotherapy, and no current clinical indication for chemotherapy.
* 4. Previously received at least one, up to two lines of systemic therapy (including at least one line of endocrine therapy combined with CDK4/6 inhibitor therapy).
* 5. At least one measurable lesion according to RECIST 1.1 criteria.
* 6. Willing to provide tumor and/or blood samples for biomarker testing; if unable to provide, subject to investigator and sponsor evaluation for eligibility.
* 7. ECOG performance status score of 0-1.
* 8. Investigator-assessed life expectancy ≥6 months.
* 9. Adequate organ and bone marrow function.
* 10. Premenopausal female patients using LHRH agonists to suppress ovarian function must agree to use two acceptable forms of highly effective contraception during the study and for 2 years after stopping study treatment; female patients of childbearing potential must have a negative pregnancy blood test before starting study treatment and must not be breastfeeding.
* 11. Male patients must agree to use barrier contraception (i.e., condoms) during the study and for 2 years after stopping study treatment; for men with future fertility plans, sperm freezing is recommended before starting study treatment.
* 12. Participants must provide informed consent before the trial and voluntarily sign the written ICF.

Exclusion Criteria:

* 1. Previous pathological diagnosis of HER2-positive breast cancer.
* 2. Patients judged by the investigator to be unsuitable for endocrine therapy.
* 3. Patients who have previously received PI3K/AKT/mTOR inhibitors, fulvestrant, or other ER-targeted therapies (including oral SERDs, ER protein degraders PROTAC, etc.).
* 4. Received chemotherapy, radiotherapy, biological therapy, targeted therapy, immunotherapy, or other anti-tumor treatments within 4 weeks before randomization.
* 5. Received other unapproved investigational drugs within 4 weeks before randomization.
* 6. Underwent major surgery within 4 weeks before randomization or has not fully recovered from any previous invasive procedures.
* 7. Received systemic glucocorticoids (prednisone \>10 mg/day or equivalent) or other immunosuppressive treatments within 2 weeks before randomization.
* 8. Had an infection within 2 weeks before randomization requiring systemic (oral or IV) anti-infective treatment (uncomplicated urinary tract infections or upper respiratory tract infections excluded).
* 9. Received inactivated or live attenuated vaccines or COVID-19 vaccines within 4 weeks before randomization.
* 10. Used strong inhibitors or inducers of CYP3A4 hepatic metabolic enzymes within 2 weeks before randomization or still need to continue using such drugs.
* 11. Diagnosed with other malignancies within 5 years before randomization.
* 12. Suffering from severe cardiovascular or cerebrovascular diseases.
* 13. Adverse reactions from previous anti-tumor treatments have not recovered to CTCAE 5.0 grade ≤1.
* 14. Active leptomeningeal disease or poorly controlled central nervous system metastases.
* 15. Presence of pleural/abdominal effusion or pericardial effusion with clinical symptoms or requiring symptomatic treatment.
* 16. Known bleeding tendency (constitution) or coagulation disorders.
* 17. History of severe lung diseases such as interstitial lung disease and/or pneumonia, pulmonary hypertension, or radiation pneumonitis requiring glucocorticoid treatment.
* 18. Known hypersensitivity or intolerance to any component of the study drug or its excipients, or LHRH agonists (if applicable).
* 19. History of autoimmune diseases (except tuberous sclerosis), immunodeficiency diseases, including HIV-positive, or other acquired or congenital immunodeficiency diseases, or organ transplant history.
* 20. Active HBV, HCV, syphilis, or tuberculosis infection.
* 21. Other conditions judged by the investigator to be unsuitable for participation in this study.

Primary outcomes:
measure: Progression-free Survival（PFS）
timeFrame: Up to ~24 months
Secondary outcomes:
measure: Overall Survival（OS）
timeFrame: Up to ~36 months
measure: Overall response rate（ORR）
timeFrame: Up to ~24 months
measure: Clinical benefit rate（CBR）
timeFrame: Up to ~24 months
measure: Disease control rate（DCR）
timeFrame: Up to ~24 months
measure: Duration of Response（DOR）
timeFrame: Up to ~24 months
measure: Safety and Tolerability：the incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: Up to ~24 months
measure: PK metrics：plasma concentration of sirolimus
timeFrame: Up to ~24 months
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Clinical Trials Information Group
state: Hebei
Study officials:
References: