Clinical trial NCT06680921: A Study of SIM0270 Combined with Everolimus Vs. Treatment of Physician's Choice in Patients with ER+/HER2- Advanced Breast Cancer (SIMRISE)
Official title: A Randomized, Open-label, Phase III Study of SIM0270 Combined with Everolimus Versus Treatment of Physician's Choice in Patients with CDK4/6 Inhibitors Previously Treated , ER+/HER2- Locally Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Locally Advanced or Metastatic Breast Cancer
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Nanjing Zaiming Pharmaceutical Co., Ltd.
First posted: 2024-11-08
Enrollment: 460
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: This Phase III, randomized, open label, multicenter study will evaluate the efficacy and safety of SIM0270 combined with everolimus compared to physician's choice of treatment in subjects with ER+/HER2- locally advanced or metastatic breast cancer who have had previous treatment with CDK4/6 inhibitor.


Eligibility criteria: Inclusion criteria:

1. Subjects with histologically or cytologically confirmed ER+/HER2- locally advanced or metastatic breast cancer
2. Subjects must have at least one RECIST 1.1 measurable disease and /or at least 1 lytic or mixed (lytic + sclerotic) bone lesion
3. For women who are post menopausal must meet criteria as defined in the protocol.For women who are premenopausal or perimenopausal and for men: treatment with approved LHRH agonist therapy for screening period and the duration of study treatment
4. Have disease that has demonstrated progression on or after prior treatment:

   1. subjects had received 1 to 2 endocrine therapies in the locally advanced or metastatic setting with disease recurrence/disease progression while being treated with adjuvant endocrine therapy for ≥ 24 months and/or endocrine therapy in the locally advanced or metastatic setting, and derived a clinical benefit from therapy
   2. subjects had received ≤ 1 chemotherapy in the locally advanced or metastatic setting.
5. Eastern Cooperative Oncology Group Performance Status 0-1
6. Adequate organ function

exclusion criteria:

1. Prior treatment with a oral selective estrogen receptor degrader (SERD) or other investigational-ER-directed therapy, or any PI3K-AKI-mTOR inhibitors
2. Treatment with any investigational therapy within 28 days prior to study treatment.Treatment with moderate/strong CYP3A inhibitors or P-gP inhibitor within 14 days prior to first dose or moderate/strong CYP3A inducer within 28 days prior to first dose
3. Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
4. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
5. Active cardiac disease or history of cardiac dysfunction, as defined in the protocol
6. Pregnant or breastfeeding

Primary outcomes:
measure: Progression free survival(PFS) , as assessed by blinded independent review committee(BIRC) according to RECIST1.1
timeFrame: 2 year
Secondary outcomes:
measure: Progression free survival(PFS) , as assessed by investigator according to RECIST1.1
timeFrame: 2 year
measure: Overall Survival (OS)
timeFrame: 3 year
measure: The incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 3 year
measure: Blood concentrations
timeFrame: At five specified time points of the first 6 cycles (each cycle is 28 days)
measure: Objective Response Rate (ORR) by investigator
timeFrame: 2 year
measure: Objective Response Rate (DOR) by investigator
timeFrame: 2 year
measure: ORR by BIRC
timeFrame: 2 year
measure: DOR by BIRC
timeFrame: 2 year
measure: Clinical benefit rate(CBR) by investigator
timeFrame: 2 year
measure: CBR by BIRC
timeFrame: 2 year
measure: Time To Progression (TTP) by investigator
timeFrame: 2 year
measure: Time To Progression (TTP) by BIRC
timeFrame: 2 year
measure: Change from baseline in EQ-5D-5L scores
timeFrame: 2 year
measure: Change from baseline in FACT-B scores
timeFrame: 2 year
Other outcomes:
Locations:
city: Haerbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: