Advanced HR-positive and HER2-negative Breast Cancer; CDK4/6 Inhibitor Treatment Failed
Conditions
Brief summary
This is a single-arm, Phase II clinical study to explore the efficacy and safety of dalpiciclib combined with fluvestrant and compound gossypol acetate tablets in advanced HR-positive and HER2-negative breast cancer after CDK4/6 treatment failed.
Detailed description
Dalpiciclib: According to the standard dose, 150mg orally for three weeks and stop for one week. Fluvestrant: At the standard dose, 500mg once every four weeks. A further 500mg dose two weeks after the first dose. Compound gossypol acetate tablets: 20mg once a day.
Interventions
DRUGdalpiciclib; fluvestrant; compound gossypol acetate tablets
Darcilie: 150mg orally for three weeks and stop for one week. Fluvestrant: 500mg every four weeks. A further 500mg dose two weeks after the first dose. Compound gossyrol acetate tablet: 20mg daily.
Sponsors
Zhejiang Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.Written informed consent. 2.Women aged 18 years or older. 3.Eastern Cooperative Oncology Group(ECOG) has a physical fitness score of 0 or 1. 4.Life expectancy is more than six months. 5.Diagnosed as HR-positive HER2-negative metastatic breast cancer. 6.There was at least one measurable lesion according to RECIST 1.1. 7.Failed in treating with CDK4/6 inhibitors combined with endocrine therapy at the metastatic stage. 8.Good organ function. 9.Fertile female patients must have a negative serum pregnancy test within seven days prior to study treatment and consent to effective contraceptive use for 180 days from screening to the last dose of study treatment. 10.Female patients must agree not to breastfeed during the study period or for 180 days after the last dose of study therapy.
Exclusion criteria
1.Patients enrolled in any interventional clinical trial at the same time and received the investigational therapy ≤ four weeks prior to initiation of the regimen or at least five half-lives of the investigational drug. 2.Patients who had received radiation therapy with bone marrow coverage \>20% within two weeks before the start of treatment, except for minor palliative radiation therapy more than one week before the first day of the study. 3.Patients with a visceral crisis, and requiring chemotherapy. 4.Patients allergic to dalpiciclib or compound gossyrol acetate tablets. 5.A history of platelet transfusion for chemotherapy-induced thrombocytopenia or prior cancer treatment (lasting \> 4 weeks and associated with recent treatment) is known to result in ≥ grade 3 hematological toxicity. 6.The patient had any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). 7.Patients have a severe, uncontrolled medical condition, a non-malignant systemic disease, or an active, uncontrolled infection. 8.Patients diagnosed, detected, or treated for another type of cancer within ≤2 years prior to beginning regimen therapy. Patients with brain metastases or pial metastases uncontrolled. 9.Patients have received an allogeneic bone marrow transplant or double umbilical cord blood transplant. 10.Patients cannot swallow oral medications. 11.Patients with gastrointestinal disorders that may interfere with the absorption of investigational drugs. 12.Patients have had systemic active autoimmune disease (i.e., disease modulators, corticosteroids, or immunosuppressants) within the past two years. 13.Patients with a history of human immunodeficiency virus, active-hepatitis -B or C. 14.Pregnant or nursing women. Fertile adults without effective contraceptive methods.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to 24 months | ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | up to 24 months | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. |
| Clinical Benefit Rate (CBR) | up to 24 months | Percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST v1.1. |
| Duration of Overall Response(DoR) | up to 24 months | Time from first recording to CR or PR to disease progression or all-cause death. |
| Overall survival (OS) | up to 24 months | Time to death from any cause from the date of first dose of study treatment |
| adverse event(AE) | Throughout the experiment, assessed up to 24 months. | Evaluation performed using the National Cancer Institute (NCI)- Standard for Common Terminology for Adverse Events (CTCAE)v.5.0. |
| Time to response (TTR) | up to 24 months | TTR defined as the time from the date of the first dose of study treatment to the first objective tumor response when CR or PR is observed. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory endpoint | Throughout the experiment, assessed up to 24 months. | Correlation between the expression levels of LRPPRC and CDK6 and the efficacy of Dalpiciclib combined with Fulvestrant and Compound Gossyfol Acetate Tablets. |
Countries
China
Outcome results
None listed