A Single Arm Phase II Study to Evaluate Efficacy of T-DM1 With Palbociclib in the Treatment of Patients With Metastatic HER2 Positive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 16
- 主要终点
- Estimate Progression-free Survival
研究概览
简要总结
This is a single arm, phase II study to evaluate if the combination of T-DM1 with palbociclib improves progression-free survival in patients with metastatic HER2 positive breast cancer. All patients will be treated with T-DM1 with palbociclib.
详细描述
This is a multi-center, single arm, phase II study of T-DM1 with palbociclib in the treatment of patients with metastatic HER2-positive breast cancer.
Hypotheses: Combination of T-DM1 with palbociclib improves progression free survival
Primary objective: Progression free survival of the combination of T-DM1 with palbociclib
Secondary objectives i) Response rates ii) Overall survival
Correlative objectives i) Investigate predictive biomarkers of response in blood and archived tumor tissue ii) Investigate mechanisms of resistance for palbociclib in blood and tumor tissue
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be informed of the investigational nature of the study and all pertinent aspects of the trial
- •Sign and provide written consent in accordance with institutional and federal guidelines.
- •ECOG Performance status of 0-2
- •Recurrent or metastatic HER2-positive breast cancer (HER2 positive is defined per ASCO-CAP guidelines)
- •Adequate cardiac reserve (EF≥50%)
- •Serum creatinine ≤ 1.5 x institutional upper limit of normal (IULN), bilirubin ≤ 2.0, and an SGOT/SGPT/alkaline phosphatase ≤ 2.0 x IULN
- •Adequate bone marrow function (ANC ≥1000, Platelets ≥100,000/ml, Hemoglobin ≥10gm/dL)
- •Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures
- •Been treated with pertuzumab previously (neoadjuvant or metastatic setting). Patients who weren't able to tolerate pertuzumab due to side effects can be eligible for study upon discussion with the study PI
- •No more than 2 lines of therapy in the metastatic disease setting
排除标准
- •HER2 negative tumors
- •Prior treatment with T-DM1
- •Prior treatment with CDK 4/6 inhibitors
- •Known active CNS metastases or carcinomatous meningitis. Patients with stable CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. However, oral corticosteroids for control of CNS symptoms are not allowed on study
- •Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs.
- •Uncontrolled systemic illness, including but not limited to ongoing or active infection
- •Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
- •Be pregnant or breast feeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment and must agree to use effective contraception during the period of therapy
- •Concurrent hormonal or other anti-neoplastic therapy is not allowed. Patients can receive supportive therapy like bone-directed therapy including bisphosphonates or denosumab
研究组 & 干预措施
T-DM1 with palbociclib
T-DM1 is given intravenously every 21 days (day 1 of each cycle) Palbociclib is administered orally on days 5-18 of each cycle
干预措施: Palbociclib (Drug)
T-DM1 with palbociclib
T-DM1 is given intravenously every 21 days (day 1 of each cycle) Palbociclib is administered orally on days 5-18 of each cycle
干预措施: T-DM1 (Drug)
Single Agent T-DM1
T-DM1 is given intravenously every 21 days (day 1 of each cycle)
干预措施: T-DM1 (Drug)
结局指标
主要结局
Estimate Progression-free Survival
时间窗: Up to 4 years
Progression Free Survival (PFS) is defined as the time from date of first treatment to the date of investigator-determined objective disease progression as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 or death from any cause. Per RECIST 1.1 for target lesions: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Patients who have neither progressed nor died will be censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post initiation (that is post baseline) radiographic assessment is available.
次要结局
- Number of Participants With Response(Up to 4 years)
- Estimate Overall Survival(Up to 4 years)