HR-positive, HER2-negative Metastatic Breast Cancer With Brain Metastases
Conditions
Brief summary
This study aims to evaluate the efficacy and safety of adding the anti-angiogenic agent anlotinib to the combination of the CDK2/4/6 inhibitor Culmerciclib and endocrine therapy in patients with HR+/HER2- breast cancer and brain metastases. Eligible patients present with newly diagnosed brain metastases or brain metastases that progressed following prior local therapy. It is hoped that this therapeutic combination can achieve disease control in these patients.
Interventions
DRUGCulmerciclib
180 mg orally once daily
DRUGAnlotinib
12 mg orally once daily on Days 1-14 of every 3-week cycle
DRUGEndocrine Therapy
administered per approved prescribing information
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Women aged ≥ 18 years * ECOG PS of 0-1 * Life expectancy of at least 12 weeks * histologically or cytologically documented HR+/HER2- breast cancer * radiologically confirmed brain parenchymal metastases without the need for immediate local therapy * measurable brain metastasis lesion according to RANO-BM criteria * Must have active brain metastases, defined as newly diagnosed brain metastases or progressive brain metastases following prior local therapy * Prior systemic therapy must meet all the following criteria： 1. No more than 3 lines of prior systemic therapy for advanced disease 2. No more than 1 line of chemotherapy or antibody-drug conjugate (ADC) administered in the advanced setting 3. No prior CDK4/6 inhibitor therapy for advanced disease, or only 1 line of CDK4/6 inhibitor therapy with treatment duration \> 6 months * Adequate hematological, hepatic and renal function * Women of child bearing potential must agree to use a contraceptive method during the treatment period and for at least 180 days after the last dose of experiment treatment * Patients must be able to participate and comply with treatment and follow-up
Exclusion criteria
* Patients with leptomeningeal metastases, brainstem metastases or skull metastases * Prior receipt of anti-angiogenic agents or Culmerciclib * Unresolved Grade ≥2 toxicities (per CTCAE Version 6.0) attributable to any prior therapy, except alopecia * Patients with visceral crisis,defined as severe organ dysfunction assessed by symptoms, signs, laboratory examinations and rapid disease progression * Inability to swallow capsules or tablets * Any severe and/or uncontrolled medical disease * Other malignancies diagnosed within 5 years, excluding cured non-melanoma skin cancer, cervical carcinoma in situ and papillary thyroid carcinoma * Radiographic evidence of tumor invasion of major vessels, or high risk of tumor invasion into major vessels resulting in life-threatening hemorrhage as assessed by the investigator * Patients with arterial or venous thromboembolic events within 6 months, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism * Participation in other anti-tumor clinical trials within 4 weeks prior to enrollment * Any other condition that the investigator considers inappropriate to participate in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CNS progression-free survival(CNS-PFS) | From enrollment to the end of treatment at 8 months | Time from treatment until disease progression or death per RANO-BM criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| progression-free survival (PFS) | From enrollment to the end of treatment at 8 months | Time from treatment until disease progression or death |
| objective response rate (ORR) | From enrollment to the end of treatment at 8 months | Objective Response Rate (ORR) based on RECIST 1.1 criteria |
| intracranial objective response rate（IC-ORR) | From enrollment to the end of treatment at 8 months | intracranial objective response rate(ORR-IC) per RANO-BM criteria |
| Overall Survival (OS) | From enrollment to the end of treatment at 18 months | Time from treatment until death from any cause. |
| Safety and Adverse Events | From enrollment to the end of treatment at 9 months | Incidence and severity of adverse events. |
Countries
China
Contacts
CONTACTShusen Wang, MD
PRINCIPAL_INVESTIGATORShusen Wang, MD
Sun Yat-sen University CancerCenter
PRINCIPAL_INVESTIGATORCuizhi Geng, MD
Hebei Medical University Fourth Hospital
Outcome results
None listed