A Phase I Study of Herceptin/Flavopiridol in HER-2 Positive Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0
研究概览
简要总结
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with flavopiridol may kill more tumor cells. Phase I trial to study the effectiveness of combining trastuzumab with flavopiridol in treating patients who have metastatic breast cancer
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of flavopiridol in combination with Herceptin in HER-2 positive metastatic breast cancer.
SECONDARY OBJECTIVES:
I. To determine the dose of flavopiridol necessary to achieve a target plasma level of 300-500 nM of flavopiridol in combination with a fixed dose of Herceptin.
II. To assess the feasibility of measuring cyclin D1 in circulating tumor cells and tissue biopsies before and after therapy as a surrogate marker of flavopiridol activity.
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
- •Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease; patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologic study
- •Either the primary tumor or the metastasis must overexpress HER2; acceptable methods of measurement of HER2 expression include immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive for HER2 overexpression using the DAKO Herceptest or the CB-11 antibody (recently FDA approved for HER-2 testing); tumors tested by FISH must be positive by either the Vysis Pathyvision method or the Ventana INFORM method; patients may have measurable or evaluable disease
- •Patients may have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer
- •Patients may have received up to two prior Herceptin-containing regimens in the metastatic setting
- •Patients may have received prior radiation therapy in either the metastatic or early stage settings; radiation therapy must be completed at least 7 days prior to study participation
- •Patients may have received hormonal therapy (therapies) in the adjuvant or metastatic setting; patients must discontinue hormonal therapy prior to study participation
- •Life expectancy of greater than 6 months
- •ECOG performance status < 2 (Karnofsky > 60%)
- •Absolute neutrophil count >= 1,500/mm^3
- •Platelets >= 100,000/mm^3
- •Total bilirubin =< 1.5 mg/dl
- •AST(SGOT)/ALT(SGPT) =< 3 X upper limit normal
- •Creatinine =< 2.0 mg/dl
- •LVEF >= 50%
- •EKG no acute changes
- •Patients may not receive concurrent hormonal therapy, chemotherapy, or radiation treatments while on study; patients requiring radiation therapy during protocol-based treatment will be taken off study with the exception of whole brain radiation or stereotactic radiosurgery for brain metastases; protocol-based therapy will be held during the therapy and for 1 week after treatment but may be resumed; patients may not receive other experimental treatments while on study; patient receiving bisphosphonates may continue to receive treatment while on study; patients may initiate bisphosphonate therapy while on study provided that there has been no evidence of progressive disease and that the bone sites do not constitute the only sites of evaluable disease; if patients are on Lupron prior to the start of this trial, than they must continue on Lupron throughout the course of this study
- •Patients must be neither pregnant nor expect becoming pregnant or conceiving a child while on study; women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Patients who have had more than three chemotherapy regimens in the metastatic setting, more than two Herceptin-containing regimens in the metastatic setting, radiation therapy within 1 week prior to study entry, or those who have not recovered from reversible adverse events due to prior treatments for cancer, are ineligible
- •Patients with active brain metastases or leptomengingeal carcinomatosis are excluded from this clinical trial; patients with a history of treated CNS metastases are eligible if they do not have active symptoms from their CNS disease
- •Patients with a history of grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study are ineligible; patients who experienced grade 1 or 2 hypersensitivity reactions to prior Herceptin are eligible IF these reactions did not prevent further administration
- •Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
- •Pregnant women are excluded from this study
- •Patients with a contraindication to taking coumadin or other warfarin products are ineligible
研究组 & 干预措施
Treatment (trastuzumab and alvocidib)
Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: trastuzumab (Biological)
Treatment (trastuzumab and alvocidib)
Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: alvocidib (Drug)
Treatment (trastuzumab and alvocidib)
Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (trastuzumab and alvocidib)
Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0
时间窗: 3 weeks
次要结局
- Measures of circulating extracellular domain of HER-2 in plasma(Up to 3 years)
- Measures of HER-2, Cyclin D1 and activated Rb in circulating tumor cells(Up to 3 years)