PHASE 1B STUDY TO ASSESS THE SAFETY, TOLERABILITY, AND CLINICAL ACTIVITY OF GEDATOLISIB IN COMBINATION WITH PALBOCICLIB AND EITHER LETROZOLE OR FULVESTRANT IN WOMEN WITH METASTATIC OR LOCALLY ADVANCED/RECURRENT BREAST CANCER (MBC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celcuity Inc
- 入组人数
- 141
- 试验地点
- 36
- 主要终点
- Objective response rate observed in patients in the dose expansion portion
研究概览
简要总结
This is a multicenter, open label, Phase 1b study in patients with mBC. This study will have a dose escalation to identify the maximum tolerated dose (MTD) of the combination of gedatolisib plus palbociclib/fulvestrant and gedatolisib plus palbociclib/letrozole and expansion to estimate the objective response rate (OR) of the combination of gedatolisib plus palbociclib/letrozole or palbociclib/fulvestrant.
详细描述
This is a multicenter, open label, continuous Phase 1b study in patients with MBC. This study will have a dose escalation and expansion. The dose escalation will identify the maximum tolerated dose (MTD) of the combination of gedatolisib plus palbociclib/fulvestrant and gedatolisib plus palbociclib/letrozole. The expansion will estimate the objective response rate (OR) of the combination of gedatolisib plus palbociclib/letrozole and the combination of gedatolisib plus palbociclib/fulvestrant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women 18 years of age or older, who are either: Postmenopausal or Pre/perimenopausal women with medically-induced menopause by treatment with agents to induce chemical menopause.
- •Histologically or cytologically proven diagnosis of breast cancer with evidence of metastasis.
- •Documentation of estrogen receptor positive ((ER+), human epidermal growth factor receptor 2 (HER2 negative (HER2-)) tumor.
- •Dose Escalation Portion: Patients must satisfy one of the following criteria:
- •Letrozole combination cohort (L): metastatic breast cancer (MBC) with progression who are candidates for a letrozole-containing regimen, with palbociclib.
- •Fulvestrant combination cohort (F): MBC with progression who are candidates for a fulvestrant containing regimen, with palbociclib.
- •Dose Expansion Portion: Patients must satisfy one of the following criteria:
- •Arm A: MBC with progression and no prior endocrine based systemic therapy in the metastatic setting;
- •Arm B: MBC with progression during or following one prior endocrine based systemic therapy in the metastatic setting, with no prior therapy with any cyclin-dependent kinase (CDK) inhibitor;
- •Arm C/Arm D: MBC with progression during or following one or two prior endocrine based systemic therapies in the metastatic setting, and following prior therapy with a CDK inhibitor.
- •Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.
- •Bone only patients during dose escalation portion.
- •Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available.
- •Eastern Cooperative Oncology Group [ECOG] performance must be 0 or
- •Adequate bone marrow, renal and liver function.
排除标准
- •Prior treatment with a mechanistic target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinase (PI3K) inhibitor.
- •More than 1 line of prior chemotherapy in the treatment of metastatic or locally advanced/recurrent disease.
- •Bone only patients during expansion/efficacy portion.
- •Patients with advanced/metastatic disease who have symptomatic visceral spread, and who have life threatening complications needing immediate therapy, such as massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver replacement with tumor.
- •Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases.
- •Active bacterial, fungal or viral infection.
- •Uncontrolled or significant cardiovascular disease.
- •Radiation therapy within 4 weeks of investigational product.
- •Cytotoxic chemotherapy within 4 weeks of investigational product (6 weeks for mitomycin C or nitrosoureas) if immediate prior regimen was administered on an every 3 4 week schedule or 2 weeks of investigational product if immediate prior regimen consisted of weekly therapy.
- •Any other anti cancer agents (eg, hormonal, biological, investigational) within 5 times the half life prior to investigational product.
- •Impairment of gastro intestinal (GI) function or GI disease.
- •Pregnant female patients; breastfeeding female patients; and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for 90 days.
研究组 & 干预措施
Letrozole Cohort
Letrozole combination cohort in dose escalation
干预措施: Gedatolisib (Drug)
Letrozole Cohort
Letrozole combination cohort in dose escalation
干预措施: Palbociclib (Drug)
Letrozole Cohort
Letrozole combination cohort in dose escalation
干预措施: Letrozole (Drug)
Fulvestrant cohort
Fulvestrant combination cohort in dose escalation
干预措施: Gedatolisib (Drug)
Fulvestrant cohort
Fulvestrant combination cohort in dose escalation
干预措施: Palbociclib (Drug)
Fulvestrant cohort
Fulvestrant combination cohort in dose escalation
干预措施: Fulvestrant (Drug)
ARM A
Gedatolisib + palbociclib + letrozole in dose expansion
干预措施: Gedatolisib (Drug)
ARM A
Gedatolisib + palbociclib + letrozole in dose expansion
干预措施: Palbociclib (Drug)
ARM A
Gedatolisib + palbociclib + letrozole in dose expansion
干预措施: Letrozole (Drug)
ARM B
Gedatolisib + palbociclib + fulvestrant in dose expansion
干预措施: Gedatolisib (Drug)
ARM B
Gedatolisib + palbociclib + fulvestrant in dose expansion
干预措施: Palbociclib (Drug)
ARM B
Gedatolisib + palbociclib + fulvestrant in dose expansion
干预措施: Fulvestrant (Drug)
ARM C
Gedatolisib + palbociclib + fulvestrant in dose expansion
干预措施: Gedatolisib (Drug)
ARM C
Gedatolisib + palbociclib + fulvestrant in dose expansion
干预措施: Palbociclib (Drug)
ARM C
Gedatolisib + palbociclib + fulvestrant in dose expansion
干预措施: Fulvestrant (Drug)
Arm D
Gedatolisib (3:1) + palbociclib + fulvestrant in dose expansion
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Objective response rate observed in patients in the dose expansion portion
时间窗: 16 weeks
Number of patients for each response category, objective response rate (number of patients with a partial response (PR)) relative to the number of response evaluable patients)
Number of participants with dose limiting toxicities
时间窗: up to 28 days
次要结局
- Maximum observed plasma concentration(Day 1: 0, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 24, 72 and 168 hours. Cycle 2 Day 1: 0, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 24, 72 and 168 hours)
- Tumor response observed in patients in the dose escalation portion(16 weeks)
- Duration of response(16 weeks)
- QTc interval (corrected QT interval)(Screening up to 6 months)
- Progression free survival(16 weeks)