A Phase II Study of BEBT-209 in Combination With Carboplatin and Gemcitabine for the Treatment of Advanced Triple-Negative Breast Cancer
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- BeBetter Med Inc
- Enrollment
- 120
- Locations
- 2
- Primary Endpoint
- PFS
Overview
Brief Summary
This is a multicenter, open-label, two-stage Phase II clinical study to evaluate the safety and efficacy of BEBT-209 capsule in combination with carboplatin and gemcitabine for the treatment of advanced triple-negative breast cancer (TNBC).
Detailed Description
This study is designed with a total of 3 cohorts, enrolling patients with advanced triple-negative breast cancer. Subjects are randomly assigned to each cohort in a 1:1:1 ratio. Each cohort initially enrolls no fewer than 8 subjects for safety assessment, with the assessment period being the first cycle of medication (21 days). If the overall safety assessment is tolerable, the enrollment will be expanded to 30-40 subjects. During the trial, if the subjects in any of the above cohorts are unable to tolerate the treatment or there is no clinical benefit, the enrollment for that cohort will be terminated promptly.
Dosing Regimen Exploration Stage: A total of 3 cohorts are designed, namely Cohort 1, Cohort 2, and Cohort 3. Cohort 1 receives carboplatin and gemcitabine treatment, with medication administered on days 1 and 8 of each cycle, with a 21-day cycle; Cohort 2 receives BEBT-209 capsules + chemotherapy (carboplatin and gemcitabine), with medication administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle, where on days 1 and 8, BEBT-209 capsules 150mg are administered orally only before dinner, and on days 2 and 9, BEBT-209 capsules 150mg are administered orally before breakfast on the day of chemotherapy, along with carboplatin and gemcitabine treatment; Cohort 3 receives BEBT-209 capsules + chemotherapy (carboplatin and gemcitabine), with medication administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle, where on days 1 and 8, BEBT-209 capsules are administered orally only (150mg，twice a day, before breakfast and before dinner), and on days 2 and 9, BEBT-209 capsules 150mg are administered orally before breakfast on the day of chemotherapy, along with carboplatin and gemcitabine treatment. If the safety assessment deems the BEBT-209 dosing regimen in Cohort 2 and Cohort 3 to be intolerable, the investigators may adjust the dosing regimen design for BEBT-209 capsules.
Expansion Stage: Investigators determine the expansion cohort for a specific dosing regimen based on the combined results of safety and pharmacodynamics observed in the dosing regimen exploration stage, further exploring the safety and efficacy of BEBT-209 capsules in combination with carboplatin and gemcitabine for the treatment of advanced triple-negative breast cancer.
The study process for each subject includes three periods: the screening period, the treatment period, and the post-treatment follow-up period. The screening period lasts up to 28 days. Subjects who meet the inclusion criteria and do not meet the exclusion criteria will be enrolled to receive treatment in a 21-day treatment cycle. Hematological assessments are conducted before and after each cycle of chemotherapy, and an overall safety assessment is conducted according to the protocol during the study period; after the first dose during the treatment period, the first two tumor assessments are conducted every 9 weeks, and from the third assessment onward, every 12 weeks. Participants can continue to receive the study medication until disease progression (PD), death, intolerable toxicity, or withdrawal of informed consent (whichever occurs first).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age: ≥18 years old, female;
- •The subject has fully understood and is willing to sign the Informed Consent Form (ICF);
- •Confirmed diagnosis of HR-negative, HER2-negative locally recurrent or metastatic breast cancer by pathological biopsy;
- •Estrogen and progesterone receptor immunohistochemical assessment of tumor tissue is negative (defined as \<1% nuclear staining), and HER2 is negative (i.e., no overexpression, including local immunohistochemical assessment \[0 or 1+\], or immunohistochemical assessment \[2+\] with negative in situ hybridization testing);
- •The subject has previously received 1-2 lines of systemic treatment (if progression within 12 months after the last treatment of adjuvant/new adjuvant, it can be considered as one line of treatment);
- •At least one measurable lesion in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria;
- •Eastern Cooperative Oncology Group (ECOG) score of 0-1 , and no decline in physical performance in the past two weeks;
- •Life expectancy of at least 12 weeks;
- •Adequate organ and bone marrow function, defined as follows:
- •Absolute neutrophil count (ANC) ≥ 1500/mm³ (1.5 × 10\^9/L);
Exclusion Criteria
- •Previous treatment with gemcitabine;
- •Previous treatment with carboplatin for locally recurrent unresectable or metastatic breast cancer is allowed if it was administered in the adjuvant or neoadjuvant setting more than 6 months before the first metastatic relapse;
- •Concurrent central nervous system metastases or leptomeningeal disease requiring immediate radiotherapy or corticosteroid treatment; patients must discontinue steroid medication for at least 14 days before the first administration of the study drug. No stereotactic radiosurgery within 7 days or whole brain radiotherapy within 14 days before the first administration of the study drug;
- •Previous receipt of hematopoietic stem cell or bone marrow transplantation;
- •Within 7 days prior to study entry, the patient has received the following treatments:
- •Medications known to be strong inhibitors/inducers of CYP3A4;
- •Medications known to significantly prolong the QT interval or cause torsades de pointes (antiarrhythmic drugs such as quinidine, disopyramide, procainamide, sotalol, etc.);
- •Within 14 days prior to study entry, the patient has received radiotherapy, or within 21 days prior to study entry, the patient has received other investigational drug treatment or cytotoxic chemotherapy;
- •Known history of hypersensitivity or suspected allergic symptoms to any component of BEBT-209, carboplatin, or gemcitabine;
- •In a resting state, the average corrected QT interval (QTc) obtained from 3 Electrocardiogram (ECG) examinations is \>480msec (corrected using the Fridericia method); history of long QT syndrome or confirmed family history of long QT syndrome; history of clinically significant ventricular arrhythmias, or current use of antiarrhythmic drugs or implantation of defibrillation devices for the treatment of ventricular arrhythmias;
Arms & Interventions
Cohort 1：Carboplatin and Gemcitabine
Carboplatin injection, dosage:AUC 2 ×(creatinine clearance rate + 25), frequency and duration of administration: administered on days 1 and 8 of each cycle, with a 21-day cycle.
Gemcitabine hydrochloride for injection, dosage:1000mg/m², frequency and duration of administration: administered on days 1 and 8 of each cycle, with a 21-day cycle.
Intervention: Carboplatin injection (Drug)
Cohort 1：Carboplatin and Gemcitabine
Carboplatin injection, dosage:AUC 2 ×(creatinine clearance rate + 25), frequency and duration of administration: administered on days 1 and 8 of each cycle, with a 21-day cycle.
Gemcitabine hydrochloride for injection, dosage:1000mg/m², frequency and duration of administration: administered on days 1 and 8 of each cycle, with a 21-day cycle.
Intervention: Gemcitabine hydrochloride for injection (Drug)
Cohort 2：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)
BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally once before dinner, and on days 2 and 9, take orally once before breakfast.
Carboplatin injection, dosage: AUC 2 × ( creatinine clearance rate + 25), frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Intervention: BEBT-209 capsules (Drug)
Cohort 2：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)
BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally once before dinner, and on days 2 and 9, take orally once before breakfast.
Carboplatin injection, dosage: AUC 2 × ( creatinine clearance rate + 25), frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Intervention: Carboplatin injection (Drug)
Cohort 2：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)
BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally once before dinner, and on days 2 and 9, take orally once before breakfast.
Carboplatin injection, dosage: AUC 2 × ( creatinine clearance rate + 25), frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Intervention: Gemcitabine hydrochloride for injection (Drug)
Cohort 3：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)
BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally twice (before breakfast and before dinner), and on days 2 and 9, take orally once before breakfast.
Carboplatin injection, dosage: AUC 2 × (creatinine clearance rate + 25), frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Intervention: BEBT-209 capsules (Drug)
Cohort 3：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)
BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally twice (before breakfast and before dinner), and on days 2 and 9, take orally once before breakfast.
Carboplatin injection, dosage: AUC 2 × (creatinine clearance rate + 25), frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Intervention: Carboplatin injection (Drug)
Cohort 3：BEBT-209 Capsules plus Chemotherapy (Carboplatin and Gemcitabine)
BEBT-209 Capsules, dosage: 150mg, frequency and duration of administration: administered on days 1, 2, 8, and 9 of each cycle, with a 21-day cycle. On days 1 and 8, take orally twice (before breakfast and before dinner), and on days 2 and 9, take orally once before breakfast.
Carboplatin injection, dosage: AUC 2 × (creatinine clearance rate + 25), frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Gemcitabine hydrochloride for injection, dosage: 1000mg/m², frequency and duration of administration: administered on days 2 and 9 of each cycle, with a 21-day cycle.
Intervention: Gemcitabine hydrochloride for injection (Drug)
Outcomes
Primary Outcomes
PFS
Time Frame: From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Progression-free survival
AE
Time Frame: From the first administration of the study drug to 28 days after the last administration of the study drug
Adverse event
Secondary Outcomes
- OS(From date of administration until date of death from any cause,assessed up to 24 months.)
- ORR(During the treatment period, the first two assessments are conducted every 9 weeks, and starting from the third assessment, they are conducted every 12 weeks,assessed up to 24 months.)
- DCR(During the treatment period, the first two assessments are conducted every 9 weeks, and starting from the third assessment, they are conducted every 12 weeks,assessed up to 24 months.)
- TTR(During the treatment period, the first two assessments are conducted every 9 weeks, and starting from the third assessment, they are conducted every 12 weeks,assessed up to 24 months.)
- DOR(During the treatment period, the first two assessments are conducted every 9 weeks, and starting from the third assessment, they are conducted every 12 weeks,assessed up to 24 months.)