A Study of TQ-B3525 Tablets Combined With Fulvestrant Injection in Subjects With HR-positive, HER2-negative and PIK3CA Mutation Advanced Breast Cancer
- Conditions
- HR-positive, HER2-negative and PIK3CA Mutation Advanced Breast Cancer
- Interventions
- Registration Number
- NCT04355520
- Lead Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Brief Summary
This is a open-label, multicenter phase Ib study to evaluate safety and efficacy of TQ-B3525 tablets combined with fulvestrant injection in subjects with HR-positive, HER2-negative and PIK3CA mutation advanced breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 42
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Histopathologically confirmed breast cancer. 2. Hormone receptor(HR) positive and human epidermal growth factor receptor-2 (HER2) negative for primary or metastatic tumors confirmed by immunohistochemistry test.
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Agree to provide at least 10 unstained sections of tumor tissue obtained within 2 years (surgery or biopsy) for genetic mutation detection and with PIK3CA mutation positive.
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Age ≥18 years, postmenopausal women. 5. Inoperable, locally advanced recurrent and/or metastatic tumor, and has at least one measurable lesion.
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Inappropriate to receive radical resection or radiation therapy. 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
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Life expectancy ≥12 weeks. 9. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study.
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Understood and signed an informed consent form.
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Has known untreated or active CNS metastasis. 2.Previous or co-existing cancers of a different site or histology from primary breast cancer.
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Inadequate bone marrow hematopoiesis. 4. Abnormal liver function. 5. Renal abnormalities. 6. Has bleeding risk. 7. Gastrointestinal disorder. 8. Cardio-cerebrovascular anomaly. 9. Previous treatment: A) Has received fulvestrant injection; B) Has received PI3K, AKT and mTOR inhibitors; C) Has received anti-tumor treatment, including chemotherapy, radiotherapy, hormone therapy, biotherapy, immunotherapy, and surgical treatment, less than 4 weeks after the first administration; D) Has received oral targeted drugs less than 5 half-lives to the first administration; E) Has received palliative radiotherapy for non-target lesions within 2 weeks before the first administration; F) Toxicity related to previous anti-tumor treatment did not recover to ≤ grade 1, except for hair loss.
10.Has participated in other clinical trials within 30 days. 11.Has received major surgical treatment within 1 month or unhealed traumatic injury.
- Has a history of organ transplantation or hematopoietic stem cell transplantation within 60 days prior to the first administration.
13.Immunosuppressant or systemic or absorbable local hormone therapy is required to achieve the aim of immunosuppression (dose > 10mg/ day prednisone or other therapeutic hormones) and is still used within 2 weeks after the first administration.
14.Active bacterial or fungal infections diseases. 15.Human immunodeficiency virus (HIV) infection. 16.Pregnant or lactating female patients. 17.Has mental and neurological diseases. 18. With severe or poorly controlled diseases. 19. Has a history of active tuberculosis. 20. Patients have inadequate compliance to participate in this study.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TQ-B3525 tablets combined with fulvestrant injection TQ-B3525 TQ-B3525 tablets were taken orally, once daily in 28-day cycle; fulvestrant injection 500mg administered intravenously (IV) on day 1, day 15 of first cycle and on day 1 of follow-up treatment cycle. Each cycle is 28 days. TQ-B3525 tablets combined with fulvestrant injection Fulvestrant injection TQ-B3525 tablets were taken orally, once daily in 28-day cycle; fulvestrant injection 500mg administered intravenously (IV) on day 1, day 15 of first cycle and on day 1 of follow-up treatment cycle. Each cycle is 28 days.
- Primary Outcome Measures
Name Time Method Dose-limiting toxicity (DLT) up to 28 days Subjects appear the toxic reaction relate to the drug after treatment within 28 days.
- Secondary Outcome Measures
Name Time Method Cmax Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on day 1; Hour 0 of day 15; and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on day 28. Cmax is the maximum plasma concentration of TQ-B3525 or metabolite(s).
Tmax Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on day 1; Hour 0 of day 15; and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on day 28. To characterize the pharmacokinetics of TQ-B3525 by assessment of time to reach maximum plasma concentration.
Duration of Response (DOR) up to 72 weeks DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment.
Overall survival (OS) up to 72 weeks OS defined as the time from the first dose to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.
Overall response rate (ORR) assessed by investigator up to 72 weeks Percentage of participants achieving complete response (CR) and partial response (PR).
Progression-free survival (PFS) up to 72 weeks PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
Disease control rate（DCR） up to 72 weeks Percentage of participants achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).
AUC0-t Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on day 1; Hour 0 of day 15; and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24 hours post-dose on day 28. To characterize the pharmacokinetics of TQ-B3525 by assessment of time to reach maximum plasma concentration.
Trial Locations
- Locations (4)
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Cancer Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
The First Hospital of Jilin university
🇨🇳Changchun, Jilin, China
Liaoning Cancer Hospital
🇨🇳Shenyang, Liaoning, China