A Phase 1 Study of Alvocidib (Flavopiridol) in Combination With Radiation in Locally Advanced, Non-Operable Pancreatic and Extrahepatic Bile Duct Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of flavopiridol when administered biweekly in conjunction with radiation for patients with locally advanced pancreatic or extrahepatic bile duct cancer
研究概览
简要总结
Drugs used in chemotherapy work different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Flavopiridol may make the tumor cells more sensitive to radiation therapy. Phase I trial to study the effectiveness of combining flavopiridol with radiation therapy followed by gemcitabine hydrochloride in treating patients who have locally advanced, unresectable pancreatic cancer.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of flavopiridol in combination with radiotherapy followed by gemcitabine in patients with locally advanced, unresectable pancreatic cancer.
II. Determine the toxicity of this regimen in these patients.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics of flavopiridol in these patients. II. Determine, preliminarily, the therapeutic activity of this regimen in these patients.
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
- •Histologically or cytologically confirmed adenocarcinoma of the pancreas
- •No non-adenocarcinoma of the pancreas (i.e., islet cell, lymphoma, or sarcoma)
- •Locally advanced and unresectable disease defined as the following:
- •Obvious encasement of the celiac, hepatic, or superior mesenteric artery
- •Encasement of the portal or superior mesenteric vein not amenable to resection
- •Extrapancreatic extension with or without regional lymph node involvement
- •No distant metastases
- •Measurable or evaluable disease
- •Primary pancreatic tumor is considered evaluable, not measurable
- •A lymph node mass is considered measurable
- •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
- •Bilirubin no greater than 1.5 mg/dL
- •AST and ALT no greater than 2.5 times upper limit of normal
- •Creatinine no greater than 1.5 mg/dL
- •Creatinine clearance at least 60 mL/min
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No Crohn's disease or inflammatory bowel disease that would preclude study participation
- •No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
- •No other uncontrolled concurrent illness that would preclude study participation
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study participation
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior chemotherapy for this disease except gemcitabine hydrochloride-based therapy for which no radiologic evidence of distant metastatic disease exists
- •No prior flavopiridol or other cyclin-dependent kinase therapies
- •No prior radiotherapy for this disease
- •Prior curative surgery with local recurrence allowed
- •No other concurrent investigational therapy
- •No concurrent combination antiretroviral therapy for HIV-positive patients
排除标准
- 未提供
研究组 & 干预措施
Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)
Patients receive flavopiridol IV over 1 hour twice weekly (on days 1 and 4 or days 2 and 5) for 6 weeks. Concurrently, patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Four weeks after the completion of radiotherapy, patients are re-evaluated*. Beginning within 4-7 weeks after the completion of chemotherapy and radiotherapy, patients receive gemcitabine hydrochloride alone or in combination with another cytotoxic agent or gemcitabine hydrochloride combined with a targeted drug (e.g., erlotinib or bevacizumab) at the discretion of the oncologist. NOTE: *Patients whose imaging studies suggest potential curative resection are referred for a surgical evaluation before initiating gemcitabine hydrochloride therapy. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. Continued (see detailed description)
干预措施: alvocidib (Drug)
Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)
Patients receive flavopiridol IV over 1 hour twice weekly (on days 1 and 4 or days 2 and 5) for 6 weeks. Concurrently, patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Four weeks after the completion of radiotherapy, patients are re-evaluated*. Beginning within 4-7 weeks after the completion of chemotherapy and radiotherapy, patients receive gemcitabine hydrochloride alone or in combination with another cytotoxic agent or gemcitabine hydrochloride combined with a targeted drug (e.g., erlotinib or bevacizumab) at the discretion of the oncologist. NOTE: *Patients whose imaging studies suggest potential curative resection are referred for a surgical evaluation before initiating gemcitabine hydrochloride therapy. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. Continued (see detailed description)
干预措施: gemcitabine hydrochloride (Drug)
Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)
Patients receive flavopiridol IV over 1 hour twice weekly (on days 1 and 4 or days 2 and 5) for 6 weeks. Concurrently, patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Four weeks after the completion of radiotherapy, patients are re-evaluated*. Beginning within 4-7 weeks after the completion of chemotherapy and radiotherapy, patients receive gemcitabine hydrochloride alone or in combination with another cytotoxic agent or gemcitabine hydrochloride combined with a targeted drug (e.g., erlotinib or bevacizumab) at the discretion of the oncologist. NOTE: *Patients whose imaging studies suggest potential curative resection are referred for a surgical evaluation before initiating gemcitabine hydrochloride therapy. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. Continued (see detailed description)
干预措施: 3-dimensional conformal radiation therapy (Radiation)
Treatment (alvocidib, gemcitabine hydrochloride, 3DRT)
Patients receive flavopiridol IV over 1 hour twice weekly (on days 1 and 4 or days 2 and 5) for 6 weeks. Concurrently, patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Four weeks after the completion of radiotherapy, patients are re-evaluated*. Beginning within 4-7 weeks after the completion of chemotherapy and radiotherapy, patients receive gemcitabine hydrochloride alone or in combination with another cytotoxic agent or gemcitabine hydrochloride combined with a targeted drug (e.g., erlotinib or bevacizumab) at the discretion of the oncologist. NOTE: *Patients whose imaging studies suggest potential curative resection are referred for a surgical evaluation before initiating gemcitabine hydrochloride therapy. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. Continued (see detailed description)
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum tolerated dose of flavopiridol when administered biweekly in conjunction with radiation for patients with locally advanced pancreatic or extrahepatic bile duct cancer
时间窗: 6 weeks
次要结局
- Molecular correlates of apoptosis including PARP cleavage and caspase-3 activation, as well as changes in expression of p21, phosphorylation status of pRb and cyclin D1(10 weeks)