A Phase II Study of PS-341 Alone or in Combination With Irinotecan in Patients With Adenocarcinoma of the Gastroesophageal Junction (GEJ) or Stomach
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- True Response Rate Evaluated for the Combination of Irinotecan and PS341 by Response Evaluation Criteria in Solid Tumors (RECIST)
研究概览
简要总结
This phase II trial is studying how well bortezomib with or without irinotecan works in treating patients with gastroesophageal junction or stomach cancer that can not be removed by surgery. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy such as irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with irinotecan may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the response rate for the combination of irinotecan and PS 341 in patients with previously untreated adenocarcinoma of the stomach or GEJ.
II. To determine the response rate for PS341 in patients with previously treated adenocarcinoma of the stomach or GEJ.
III. To determine the toxicities and recovery from toxicities for patients receiving PS 341 alone or in combination with irinotecan IV. To perform GeneChip analysis on biopsy specimens prior to and subsequent to treatment with PS341 to determine changes in patterns of gene expression
OUTLINE: Patients are stratified (stratum 2 closed to accrual as of 9/19/2006) according to prior chemotherapy for advanced disease (yes vs no).
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
- •Patients must have histologically or cytologically confirmed adenocarcinoma of the GE junction or stomach, which is beyond the scope of surgical resection
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
- •Patients may have received adjuvant therapy for resected disease
- •Patients who have received no prior systemic therapy for advanced disease are eligible to receive PS341 + irinotecan
- •Patients are eligible for PS-341 as a single agent if they have received any number of prior regimens for gastric cancer
- •Life expectancy of greater than 6 weeks
- •ECOG performance status =< 2 (Karnofsky >= 60%)
- •Leukocytes >= 3,000/uL
- •Absolute neutrophil count >= 1,500/uL
- •Platelets >=100,000/uL
- •Total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
- •Creatinine within normal institutional limits
- •When possible, patients will undergo an esophagogastroduodenoscopy (EGD) with biopsy prior to therapy then at 24 hours after starting PS-341
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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 chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients may not be receiving any other investigational agents, concurrent radiation therapy, or other chemotherapy; patients who have had photodynamic therapy either within 4 weeks of study entry or concurrently are ineligible, unless it was used to relieve esophageal obstruction that could not be treated with laser, stent or dilatation
- •Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to PS 341 or other agents used in the study
- •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
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with PS341
- •HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
- •Patients with a concurrent malignancy are excluded (except for early stage squamous cell carcinoma of the skin or cervix which can be treated locally); patients with an advanced malignancy within the past five years are not eligible; patients with a prior malignancy who have been disease free for five years are eligible
研究组 & 干预措施
Stratum 1 (previously untreated)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV over 90 minutes on days 1 and 8.
干预措施: bortezomib (Drug)
Stratum 1 (previously untreated)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV over 90 minutes on days 1 and 8.
干预措施: irinotecan (Drug)
Stratum 2 (previously treated)
(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1.
干预措施: bortezomib (Drug)
结局指标
主要结局
True Response Rate Evaluated for the Combination of Irinotecan and PS341 by Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: Up to 6 years
CT or MRI imaging scans of measurable lesions were obtained at baseline and every 8 weeks thereafter. Responses were classified according to RECIST criteria (version 1.0)
次要结局
- Change in Patterns of Gene Expression Pre- and Post-treatment Performed by GeneChip Analysis(Baseline to 6 years)