A Phase I Study of UCN-01 in Combination With Irinotecan in Resistant Solid Tumor Malignancies (Part I) and in Triple Negative (ER-Negative, PgR-Negative, HER-2 Not-Amplified) Recurrent Breast Cancers (Part II)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- MTD of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)
研究概览
简要总结
This phase I trial is studying the side effects and best dose of giving 7-hydroxystaurosporine together with irinotecan hydrochloride in treating patients with metastatic or unresectable solid tumors, including triple-negative breast cancer (currently enrolling only patients with triple-negative breast cancer since 6/8/2007). Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving 7-hydroxystaurosporine together with irinotecan hydrochloride may help kill more cancer cells by making tumor cells more sensitive to the drug.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of UCN-01 (7-hydroxystaurosporine) and irinotecan (irinotecan hydrochloride) in patients with resistant solid tumors. (Part I [closed to accrual as of 6/8/2007]) II. Determine the dose-limiting toxicity of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) III. Determine the types of toxic effects of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) IV. Determine the anti-tumor activity in terms of overall response rate (partial response [PR] and complete response [CR]), clinical benefit rate (PR, CR, and stable disease), and time to disease progression in patients with estrogen receptor-negative, progesterone receptor-negative, and HER-2 not amplified (triple negative) locally recurrent or metastatic breast cancer treated with this regimen. (Part II) V. Determine the side effect profile of this regimen in patients with triple negative recurrent breast cancer. (Part II)
SECONDARY OBJECTIVES:
I. Determine any anti-tumor activity of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) II. Determine the pharmacokinetics of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) III. Determine the activity of the serum α-acid glycoprotein and correlate this level with free UCN-01 concentrations. (Part I [closed to accrual as of 6/8/2007]) IV. Determine the in vivo mechanisms of UCN-01 activity in these patients.
OUTLINE: This is a dose-escalation study.
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
- •Part I (closed to accrual as of 6/8/2007)
- •Histologically confirmed solid tumor that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective, including the following:
- •Gastrointestinal tract cancer
- •Lung cancer
- •Breast cancer
- •Ovarian cancer
- •Endometrial cancer
- •Cervical cancer
- •Prostate cancer
- •Head and neck cancer
- •Patients with or without measurable or evaluable disease allowed
- •Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques or ≥ 10 mm with spiral CT scan
- •Tumor markers allowed for evaluable disease
- •Positive bone scan, osteoblastic metastases, and pleural or peritoneal effusions are not considered measurable or evaluable disease
- •No known brain metastases
- •Histologically confirmed (either primary or the recurrent site) locally recurrent or metastatic breast cancer not amendable to surgery
- •Measurable disease
- •For skin lesions, documentation by color photography and estimation of lesion size with a ruler are required
- •Must have undergone prior therapy with an anthracycline and a taxane either in the adjuvant or metastatic setting
- •CNS metastasis allowed provided stable disease (i.e., no evidence of local progression) ≥ 3 months after local therapy
- •Hormone receptor status:
- •Estrogen receptor negative
- •Progesterone receptor negative
- •HER-2 not amplified by fluorescence in situ hybridization
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •More than 12 weeks
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin ≥ 10 g/dL
- •Bilirubin normal
- •AST/ALT no greater than 3 times upper limit of normal (ULN)
- •No Gilbert's disease
- •No chronic unconjugated hyperbilirubinemia
- •Creatinine no greater than 1.5 times ULN
- •Creatinine clearance at least 60 mL/min
- •No symptomatic cardiac dysfunction
- •No symptomatic pulmonary dysfunction
- •Oxygen saturation at least 90% by pulse oximetry on room air at rest and after walking 6 minutes
- •No insulin-dependent diabetes mellitus
- •No other uncontrolled concurrent illness
- •No active or ongoing infection
- •No psychiatric illness or social situation that would preclude study entry
- •No prior allergic reactions attributed to compounds of similar chemical or biological composition to UCN-01 or irinotecan
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No concurrent granulocyte colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) during the first course of study
- •See Disease Characteristics (Part II)
- 另有 9 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (combination chemotherapy)
PART I: Patients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, and 22 and 7-hydroxystaurosporine IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride and 7-hydroxystaurosporine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Blood samples are collected periodically during study treatment.
PART II: (treatment of triple negative recurrent breast cancer): Patients receive irinotecan hydrochloride IV and 7-hydroxystaurosporine IV as in part I at the MTD and undergo blood sample collection.
干预措施: 7-hydroxystaurosporine (Drug)
Treatment (combination chemotherapy)
PART I: Patients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, and 22 and 7-hydroxystaurosporine IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride and 7-hydroxystaurosporine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Blood samples are collected periodically during study treatment.
PART II: (treatment of triple negative recurrent breast cancer): Patients receive irinotecan hydrochloride IV and 7-hydroxystaurosporine IV as in part I at the MTD and undergo blood sample collection.
干预措施: irinotecan hydrochloride (Drug)
Treatment (combination chemotherapy)
PART I: Patients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, and 22 and 7-hydroxystaurosporine IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride and 7-hydroxystaurosporine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Blood samples are collected periodically during study treatment.
PART II: (treatment of triple negative recurrent breast cancer): Patients receive irinotecan hydrochloride IV and 7-hydroxystaurosporine IV as in part I at the MTD and undergo blood sample collection.
干预措施: diagnostic laboratory biomarker analysis (Other)
结局指标
主要结局
MTD of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)
时间窗: Part I
Defined as the highest dose given to at least 6 patients in which =\< 1 out of 6 experience dose limiting toxicity (DLT).
Toxicities associated with irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)
时间窗: Continuously over study treatment
Graded using the Cancer Therapy Evaluation Program (CTEP) Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
Anti-tumor activity of 7-hydroxystaurosporine in combination with irinotecan hydrochloride in ER-negative, PgR-negative, HER-2 not-amplified (triple negative) recurrent breast cancer (Part II)
时间窗: Every 6 weeks
Including overall response rate (partial response \[PR\] +complete response \[CR\]), clinical benefit rate (PR+CR+stable disease \[SD\]), and time to disease progression. 95% confidence interval will be calculated. Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Side effect profile of 7-hydroxystaurosporine in combination with irinotecan hydrochloride in triple negative recurrent breast cancer (Part II)
时间窗: Continuously over study treatment
95 % confidence interval will be calculated.
DLT of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)
时间窗: Part I
次要结局
- Anti-tumor activity of the combination of irinotecan hydrochloride and 7-hydroxystaurosporine in treatment of patients with resistant solid tumor malignancies(Every 6 weeks)
- Pharmacokinetics of irinotecan hydrochloride and 7-hydroxystaurosporine when administered in combination(Weekly during the first 4 weeks of course 1)
- Serum alpha-acid glycoprotein and correlate this level with free 7-hydroxystaurosporine concentrations(Weekly during the first 4 weeks of course 1)
- In vivo mechanistic basis for 7-hydroxystaurosporine activity(Weekly during the first 4 weeks of course 1)