ER+ HER2- Advanced Breast Cancer
Conditions
Brief summary
This is a phase 1 open label multicentre study of SHR9549 administered orally in patients with advanced estrogen receptor (ER) positive human epidermal receptor 2 (HER2) negative breast cancer. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of patients. The study will determine the maximum tolerated dose(MTD). In addition, expansion cohort(s) at potential therapeutic dose(s) in patients will be enrolled to further determine the safety, tolerability, pharmacokinetics and biological activity of SHR9549.
Detailed description
A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of SHR9549 in Women with Estrogen Receptor (ER) Positive Human Epidermal Receptor (HER-2) Negative Advanced Breast Cancer
Interventions
DRUGSHR9549
If initial dosing of SHR9549 is tolerated then subsequent cohorts will test increasing doses until a maximum tolerated dose(MTD) is defined
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-70 years. * Confirmation of ER positive; HER2 negative Advanced breast cancer * Documented disease progression after at least 6 months prior endocrine therapy for ER positive breast cancer. * Receipt of ≤2 lines of prior chemotherapy for advanced disease. * Any menopausal status. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and with minimum life expectancy of 12 weeks.
Exclusion criteria
* Any anti-cancer drugs for the treatment of advanced breast cancer within 14 days of the first dose of study treatment. * Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia. * Patient who is unsuitable for endocrine therapy alone including presence of life-threatening metastatic visceral disease. * uncontrolled central nervous system metastatic disease. * Any evidence of severe or uncontrolled systemic diseases. * Inadequate bone marrow reserve or organ function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limited Toxicity (DLT) | baseline through 28 days | to determine DLT in order to assess the tolerability of SHR9549 |
| Maximum Tolerated Dose (MTD) | baseline through 28 days | to determine MTD in order to assess the tolerability of SHR9549 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall response rate (ORR) | every 8 weeks for 24 weeks and then every 12 weeks thereafter through study completion, an average of 6 months | Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1) |
| Peak Plasma Concentration (Cmax) | baseline through 12 weeks | Single and multiple dose pharmacokinetic parameters of SHR9549 at pre-defined intervals |
| Incidence of Treatment-Emergent Adverse Events | baseline through 30 days after study completion | to assess the safety of SHR9549 |
| progression free survival (PFS) | every 8 weeks for 24 weeks and then every 12 weeks thereafter through study completion, an average of 6 months | Antitumour activity evaluation by following up patients' progression and survival |
| Area under the plasma concentration versus time curve (AUC) | baseline through 12 weeks | Single and multiple dose pharmacokinetic parameters of SHR9549 at pre-defined intervals |
Countries
China
Outcome results
None listed