2023-503846-30-00进行中（未招募）1/2 期
A Phase 1b/2 Open-Label Study of Samuraciclib in Combination with Elacestrant in Participants with Metastatic or Locally Advanced Hormone-Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer
适应症
试验速览
- 阶段
- 1/2 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 15
- 主要终点
- • Phase 1b (Dose-finding): ): Identification of combination, Phase 2, expansion dose level. Dose- limiting toxicities and type, incidence, severity (as graded by CTCAE v5.0), seriousness, and relationship to study medications of AEs and any laboratory abnormalities
研究概览
简要总结
• Phase 1b (Dose Finding): Determine the recommended Phase 2 dose (RP2D) of samuraciclib and elacestrant in combination. • Phase 2 (Expansion): To assess the efficacy of samuraciclib and elacestrant in combination in terms of progression-free survival (PFS) as per local investigator assessment.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Phase 2 (Expansion): assess efficacy of samuraciclib and elacestrant in combination in terms of PFS
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of carcinoma of the breast with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent.
- •Documentation of ER-positive with or without progesterone receptor (PgR)-positive tumor based on most recent tumor biopsy utilizing an assay consistent with local standards. • ER-positivity is defined as ≥10% positive stained cells regardless of the PgR-result (Hammond et al., 2010; Allison et al., 2020).
- •Documentation of HER2 negativity based on local testing on most recent tumor biopsy. • HER2-negativity is defined as immunohistochemistry score 0/1+ or negative by in situ hybridization (fluorescent in situ hybridization [FISH]/chromogenic in situ hybridization [CISH]/silver-enhanced in situ hybridization [SISH] defined as a HER2/chromosome 17 FISH (CEP17) ratio <2 or for single probe assessment a HER2 copy number <4 • Biopsy of first recurrence is recommended, in case no tumor biopsy was performed after initial resection of the primary tumor, the original tumor tissue serves as basis for assessment of ER/PgR and HER2 status • Assessment of ER, PgR, and HER2 status will be based on results from local pathology laboratories.
- •Must have 1 of the following as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: • Measurable disease • Bone only disease with evaluable lesions. Participants who have had prior radiation to bone must have at least 1 evaluable lesion in a nonirradiated area. For clarity bone lesions must be evaluable, but do not need to be measurable.
- •Participants must have documented objective disease progression while on or within 6 months after the end of the most recent therapy.
- •Participants must have received an aromatase inhibitor in combination with a CDK4/6 inhibitor in one of the following settings: • Participants must have received at least 6 months of clinical benefit on this line of therapy to be eligible. Participants who received <6 months CDK4/6 inhibitor due to tolerability issues may still enter the study provided at least 6 months aromatase inhibitor was received. • Adjuvant setting, if the disease-free interval between initiation of endocrine therapy and first line treatment of locally advanced or metastatic disease was >24 months.
- •Expected life expectancy of greater than 12 weeks.
排除标准
- •Prior therapy with a Selective estrogen receptor degrader (SERD) or other investigational SERDs or alike agents in the advanced/metastatic setting.
- •Prior treatment with cytotoxic chemotherapy for locally advanced or metastatic BC.
- •Prior treatment with a mammalian target of rapamycin (mTOR) inhibitor including, but not limited to, everolimus.
- •Inadequate hepatic, renal, bone marrow, or cardiac function, specified as follows: • Hepatic • Renal • Bone marrow • Cardiovascular
- •Known central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease.
- •More than 1 line of endocrine treatment for locally advanced or metastatic disease treatment
- •Inflammatory BC
- •Prior treatment with a phosphatidylinositol-3-kinase (PI3K) inhibitor, including, but not limited to alpelisib.
- •Prior treatment with an AKT (protein kinase B, or Akt) inhibitor, including, but not limited to capivasertib.
结局指标
主要结局
• Phase 1b (Dose-finding): ): Identification of combination, Phase 2, expansion dose level. Dose- limiting toxicities and type, incidence, severity (as graded by CTCAE v5.0), seriousness, and relationship to study medications of AEs and any laboratory abnormalities
• Phase 1b (Dose-finding): ): Identification of combination, Phase 2, expansion dose level. Dose- limiting toxicities and type, incidence, severity (as graded by CTCAE v5.0), seriousness, and relationship to study medications of AEs and any laboratory abnormalities
• Phase 2 (Expansion): PFS, defined as the time from enrollment until disease progression or death
• Phase 2 (Expansion): PFS, defined as the time from enrollment until disease progression or death
次要结局
- • Type, incidence, severity (as graded by CTCAE v5.0), seriousness, and relationship to study medications of AEs and any laboratory abnormalities
- • Clinical benefit response (CBR) 24 weeks (a complete or partial response, or stable disease (SD) for at least 24 weeks).
- • Overall Response Rate (ORR), defined as the proportion of participants with a reduction in tumor burden (PR and/or CR in accordance with RECIST v1.1) of a predefined amount
- • Duration of Response (DOR), defined as the time from documentation of tumor response (PR and/or CR) to disease progression.
- • Best percent change in tumor size.
- • Plasma concentrations and PK parameters of samuraciclib
- • Plasma concentrations and PK parameters of elacestrant
- • Correlations between ESR1 and TP53 mutations and efficacy/safety findings in this participant population
研究者
Sheila O'Mahony
Scientific
Carrick Therapeutics Limited
研究点 (15)
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