A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of IPI-504 in Combination With Trastuzumab in Patients With Pretreated, Locally Advanced or Metastatic Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 11
- 主要终点
- The primary objective of the study is to evaluate overall response rate, safety, and tolerability of IPI-504 plus trastuzumab in patients with pretreated, locally advanced or metastatic HER2 positive breast cancer
研究概览
简要总结
The purpose of this study is to see if IPI-504 in combination with trastuzamab is an effective treatment in HER2 positive metastatic breast cancer
详细描述
Recent clinical data has demonstrated that even in heavily pretreated patients with trastuzumab-refractory HER-2 positive breast cancer, targeting HER2 is efficacious.
IPI-504 is an HSP90 inhibitor and is chemically related to 17-AAG and it has been studied in a clinical trial in combination with trastuzamab and a response rate of 26% (7/27) was demonstrated in patients with pretreated, HER2-positive breast cancer. These data provide a strong scientific rationale for clinical testing of IPI-504 plus trastuzumab in patients with pretreated, locally advanced or metastatic HER2-positive breast cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Locally advanced/metastatic breast cancer.
- •HER2-expressing primary or metastatic tumor
- •Two prior regimens with HER
- •Trastuzumab must have been given. No limit to prior therapies
- •Measurable disease with RECIST 1.1
- •Clinical progression
- •ECOG 0 or 1
- •Last dose of chemotherapy, radiotherapy, surgery, ablative therapy, tyrosine kinase inhibitor, ≥2 weeks
- •Administration of biological therapy ≥4 weeks
- •Last dose of trastuzumab must be ≥1, or ≥3 weeks prior to start, if previously administered on an every 3 week schedule.
- •Resolution of toxic effects to baseline or Grade 1, except alopecia (NCI CTCAE Version 3.0
- •Organ and marrow function:
- •Hemoglobin ≥8.0 g/dL
- •ANC ≥1200/µL
- •Platelets ≥75,000 /µL
- •ALT and AST ≤ 1.5 x ULN
- •Alkaline phosphatase ≤2.5 x ULN, or ≤3.0 x ULN if secondary to liver metastases.
- •Serum bilirubin WNL
- •Serum albumin ≥3.0 g/dL
- •PT, PTT ≤1.5 x ULN
- •Serum creatinine ≤1.5 x ULN
- •Negative pregnancy test
排除标准
- •Prior treatment with Hsp90 inhibitor.
- •Grade 4 AE secondary to trastuzumab. Grade 3/4 infusion reactions or Grade 3/4 symptomatic heart failure
- •Medication/food that is a CYP3A inhibitor or inducer.
- •Hx 6 months: cardiac disease - acute coronary syndrome or unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, cirrhotic liver disease, cerebrovascular accident or significant co-morbid condition
- •Grade 3 or 4 hemorrhagic event within 6 months.
- •HIV positivity
- •Baseline QT corrected, QTcF >470 ms
- •Sinus bradycardia <50 bpm Secondary to pharmacologic therapy may enroll if stopping therapy normalizes heart rate.
- •Malignancies within 3 years other than non-melanomatous skin cancers, non-muscle-invasive bladder cancer and carcinoma in situ of cervix.
- •Active keratitis or keratoconjunctivitis
- •Active brain metastasis (e.g., requiring therapy with steroids or radiation therapy; or with intracranial progression 4 weeks after the completion of radiation therapy) uncontrolled seizure disorder, ongoing spinal cord compression, or carcinomatous meningitis. If clinically stable brain metastasis (previously treated or untreated)are present pt is eligible.
研究组 & 干预措施
IPI-504 and Trastuzumab
IPI-504 IV infusion 300 mg/m2 once weekly in combination with trastuzumab infusion every 3 weeks. (Continuous schedule)
Three week cycle with IPI-504 twice per week for 2 weeks and trastuzumab once per cycle followed by one week without treatment.
Trastuzumab IV infusion 8 mg/kg as the first dose of trastuzumab, followed by trastuzumab 6 mg/kg every 3 weeks. Subjects whose last dose of trastuzumab was <4 weeks prior to study entry will receive 6 mg/kg as the first dose of trastuzumab. For all additional cycles in Stage 1, trastuzumab will be administered with the first dose of IPI-504.
IPI-504 and trastuzumab will be administered for all cycles. Until progression or unacceptable toxicity develops.
干预措施: IPI-504 (Drug)
IPI-504 and Trastuzumab
IPI-504 IV infusion 300 mg/m2 once weekly in combination with trastuzumab infusion every 3 weeks. (Continuous schedule)
Three week cycle with IPI-504 twice per week for 2 weeks and trastuzumab once per cycle followed by one week without treatment.
Trastuzumab IV infusion 8 mg/kg as the first dose of trastuzumab, followed by trastuzumab 6 mg/kg every 3 weeks. Subjects whose last dose of trastuzumab was <4 weeks prior to study entry will receive 6 mg/kg as the first dose of trastuzumab. For all additional cycles in Stage 1, trastuzumab will be administered with the first dose of IPI-504.
IPI-504 and trastuzumab will be administered for all cycles. Until progression or unacceptable toxicity develops.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
The primary objective of the study is to evaluate overall response rate, safety, and tolerability of IPI-504 plus trastuzumab in patients with pretreated, locally advanced or metastatic HER2 positive breast cancer
时间窗: After initial 20 patients are enrolled and treated for one cycle - if less that 33% of the subjects experience a dose limiting toxicity an additional 26 subjects will be enrolled
次要结局
- Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS)(One year)