NCT01265927已完成1 期
A Phase I Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Determine the dose-limiting toxicity of GRN163L in combination with trastuzumab in patients with refractory HER2+ metastatic disease
研究概览
简要总结
A study to evaluate safety and biologic effects of giving GRN163L in combination with trastuzumab in patients diagnosed with HER2+ metastatic breast cancer that is resistant to therapy with trastuzumab.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females 18 years or older at the time of consent.
- •ECOG performance status of 0-2 within 21 days of study registration.
- •Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. NOTE: locally recurrent disease must not be amenable to surgery or radiation with curative intent.
- •Measurable or evaluable disease according to RECIST v1.1 within 35 days prior to study registration.
- •Disease must be amenable to biopsy (image-guided or via direct visualization of superficial lesions) with minimal risk to the patient. NOTE: Patients with disease limited to the lung and/or pleura are excluded.
- •Disease must be HER2+ as defined by IHC 3+ or FISH ratio > 2.
- •Resistant to trastuzumab as defined as (1) progression within 12 months of completing adjuvant/neoadjuvant trastuzumab or (2) progression on trastuzumab administered for metastatic disease.
- •Prior treatment with lapatinib or investigational HER2 targeted therapies is allowed but not required. There are no limits on the number of regimens or other prior anti-HER2 therapies patients have received.
- •LVEF ≥ Lower Limit of Normal based on MUGA or ECHO within 35 days prior to study registration
- •Females of childbearing potential and males must be willing to use an effective method of contraception from the time consent is signed until 6 months after treatment discontinuation. Methods of contraception include hormonal birth control (oral contraceptives, patch, injection, vaginal ring or implant), two barrier methods of birth control, abstinence and/or other methods as determined by the treating physician.
- •Females of childbearing potential must have a negative pregnancy test within 14 days prior to registration for protocol therapy.
- •NOTE: Females are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (> 12 months since last menses).
- •Laboratory values must be obtained within 21 days of study registration:
- •Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
- •Platelets ≥ 100 K/mm3
- •Hemoglobin (Hgb) ≥ 9.0 g/dL (may be transfused)
- •Serum creatinine < 3.0 mg/dL
- •Total Bilirubin ≤ 1.5 x ULN
- •AST/SGOT ≤ 2.5 x ULN. If liver metastases is present, AST ≤ 5 x ULN
- •ALT, SGPT ≤ 2.5 x ULN. If liver metastases is present, ALT ≤ 5 x ULN
排除标准
- •No Investigational therapy within 4 weeks of study registration
- •No hormonal therapy within 2 weeks of study registration
- •No cytotoxic chemotherapy within 2 weeks of study registration.
- •No prior treatment with GRN163L
- •No prior history of severe reaction to trastuzumab, as determined by the treating physician.
- •No history of clinically significant cardiac dysfunction, including:
- •Current uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg), or unstable angina History of symptomatic CHF (Grade >3 by NCI CTCAE or Class >II by NYHA criteria [see Appendix IV]) or serious cardiac arrhythmia requiring treatment within 12 months of study registration, with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia History of myocardial infarction within 6 months of study registration
- •No history of cerebrovascular accident within 12 months of study registration
- •No active CNS metastases. Patients with previously treated CNS metastases who do not require chronic steroids or anticonvulsants are eligible.
- •Prior radiation therapy must not have involved > 25% of bone marrow due to potential myelosuppression with GRN163L. See bone marrow chart in Appendix III
- •NOTE: Radiation therapy within 2 weeks of study registration is not allowed.
- •Females must not be breastfeeding.
- •No clinically significant active infection, as determined by the treating physician
研究组 & 干预措施
GRN163L + Trastuzumab
Experimental
干预措施: GRN163L in combination with trastuzumab (Drug)
结局指标
主要结局
Determine the dose-limiting toxicity of GRN163L in combination with trastuzumab in patients with refractory HER2+ metastatic disease
时间窗: End of Study
次要结局
- Tumor samples analyzed for activation of HER2 family signaling protein activation (phosphorylation) status prior to treatment and immediately prior to cycle 2.(Until cycle 2)
- Tumor biopsy and bone marrow aspirate assayed for telomerase activity prior to treatment and immediately prior to planned cycle 2(Until cycle 2)
- Flow cytometry to compare cell cycle distribution in tumor and bone marrow prior to treatment and immediately prior to cycle 2.(Until cycle 2)
- Determine objective response rate (ORR) and progression free survival (PFS) of GRN163L in combination with trastuzumab in this patient population(End of Study)
- Measure the concentration of trastuzumab and GRN163L from blood samples immediately before and after infusion on day 1, weekly during cycle 1, and immediately prior to cycle 2(Until cycle 2)
研究者
研究点 (1)
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