HR Positive HER2 Negative Advanced Breast Cancer
Conditions
Brief summary
This study is a prospective, open-label, randomized, multicenter, two-cohort phase II clinical trial. Starting from December 1, 2024, it plans to enroll 120 patients with advanced first-line HR-positive, HER2-negative breast cancer. A centralized randomization system (IWRS) will be used for randomization, and stratification will be performed based on the following factors during randomization: 1) Visceral metastasis (yes vs no); 2) Disease-free interval (previously untreated vs 12 \< DFI ≤ 24 vs DFI \> 24). Cohort A: Dalpiciclib 125mg + Letrozole 2.5mg Cohort B: Dalpiciclib 150mg + Letrozole 2.5mg Imaging assessment will be conducted in accordance with the RECIST 1.1 criteria, and tumor imaging evaluation will be performed by investigators from the participating centers. Patients receiving dalpiciclib will undergo a safety visit 28 days after the last dose, followed by survival follow-up until the patient's death or trial termination (whichever comes first). Pharmacokinetic assessment: Blood samples will be collected once before dosing on Cycle 1 Day 15 (C1D15), 4 hours after dosing on C1D15, before dosing on Cycle 2 Day 1 (C2D1), and before dosing on Cycle 4 Day 1 (C4D1) to explore the population pharmacokinetic characteristics of dalpiciclib and the factors affecting its pharmacokinetics. The first dosing time of the subjects, each blood collection time, the dalpiciclib dosing time within three days before blood collection, and the dalpiciclib dosing time on the day of C1D15 blood collection must be accurately recorded. If dalpiciclib is not administered within 14 days before the planned PK blood collection, no PK blood collection will be performed on the day of that visit. If possible, PK samples should be collected simultaneously with samples for other laboratory tests.
Interventions
Oral administration, 125mg，Dalpiciclib is administered for 3 weeks, followed by 1 week of rest
Oral administration, 150mg，Dalpiciclib is administered for 3 weeks, followed by 1 week of rest
DRUGLetrozole 2.5mg
Oral administration, 2.5mg, administered once daily until disease progression or unacceptable toxicity
Sponsors
wanghaibo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Female patients aged ≥18 years and ≤75 years, who are postmenopausal or premenopausal/perimenopausal, and meet one of the following conditions: 1. Have undergone bilateral oophorectomy in the past, or be aged ≥60 years; or 2. Aged \<60 years, in a natural postmenopausal state (defined as spontaneous cessation of regular menstruation for at least 12 consecutive months without other pathological or physiological causes), with E2 and FSH at postmenopausal levels; or 3. Premenopausal or perimenopausal female patients can also be enrolled, but must be willing to receive LHRH agonist treatment during the study period * Patients with breast cancer confirmed by pathological examination to be HR-positive and HER2-negative, with evidence of focal recurrence or metastasis, not suitable for surgical resection or radiotherapy with the goal of cure, and without clinical indications for chemotherapy. 1. ER-positive and/or PR-positive is defined as: the proportion of tumor cells with positive staining among all tumor cells is ≥1% (reviewed and confirmed by the investigator at the participating trial center); 2. HER2-negative is defined as: standard immunohistochemistry (IHC) test result is 0/1+; ISH test shows that the HER2/CEP17 ratio is less than 2.0 or the HER2 gene copy number is less than 4 (reviewed and confirmed by the investigator at the participating trial center) * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 * Have not previously received any systemic antineoplastic treatment for focal recurrent or metastatic disease * Have measurable lesions in line with RECIST 1.1 criteria or only bone metastatic lesions (including osteolytic lesions or mixed osteolytic/osteoblastic lesions) * Have sufficient organ and bone marrow function * Women of childbearing potential must be willing to use a medically approved highly effective contraceptive method during the study period and within 3 months after the last administration of the study drug * All acute toxic effects of previous antineoplastic treatment have resolved to grade 0-1 (according to NCI-CTCAE Version 5.0) or to the level specified in the inclusion/
Exclusion criteria
. Except for other toxicities such as alopecia that the investigator deems to pose no safety risk to the patient * Have given informed consent and signed the informed consent form, and be willing and able to comply with the planned visits, study treatment plan, laboratory tests and other trial procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression - Free Survival (PFS) | From date of randomization until the date of first documented disease progression or death from any cause (whichever comes first), assessed per RECIST 1.1 criteria up to 104 weeks | Progression - Free Survival (PFS) is registered as 'Primary' as the most clinically impactful endpoint; other outcomes (ORR, DoR) are secondary per platform requirements, though protocol does not hierarchy |
| Duration of Response (DoR) | From the date of first documented complete response (CR) or partial response (PR) (per RECIST 1.1, assessed by investigators via imaging) until the date of first documented disease progression (per RECIST 1.1) or recurrence, assessed up to 104 weeks | Time from first documentation of complete response (CR) or partial response (PR) to disease progression (per RECIST 1.1) or recurrence, assessed by investigators via imaging |
Other
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate, ORR | From date of randomization until the date of first documented disease progression or trial completion (whichever comes first), assessed per RECIST 1.1 criteria up to 104 weeks | Proportion of participants with complete response (CR, disappearance of all target lesions) or partial response (PR, ≥ 30% reduction in sum of target lesion diameters) per RECIST 1.1. |
| Overall Survival (OS) | From date of randomization until the date of death from any cause, assessed up to 208 weeks (4 years) | Time from randomization to death from any cause, with survival status monitored until trial completion or participant withdrawal. |
| Patient - Reported Outcome (PRO): Quality of Life | From baseline, then every 3 weeks during study treatment, until the date of trial completion (assessed up to 104 weeks)] | Quality of life assessed via EORTC QLQ - C30 questionnaire (score range: 0-100; for functional domains, higher scores indicate better quality of life; for symptom domains, higher scores indicate more severe symptoms), focusing on physical, emotional, and functional well - being. Administered at baseline, then every 3 weeks during treatment until trial completion. |
| Safety: Adverse Event Profile | From first dose until 30 days after last dose, monitored continuously | Adverse events (AEs) assessed by CTCAE v5.0 criteria, including type, severity, and duration. Monitored from first dose until 30 days after last dose |
Countries
China
Contacts
Primary Contacthaibo Wang
Outcome results
None listed