A Phase I Study of Antisense Bcl-2 Oligonucleotide (G3139) in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) defined as the highest safely tolerated dose where at most 1 patient experiences a dose-limiting toxicities (DLT) and the next higher dose having at least 2 patients who experience DLT
研究概览
简要总结
Phase I trial to study the effectiveness of combining carboplatin and paclitaxel with oblimersen in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of carboplatin and paclitaxel by making tumor cells more sensitive to the drugs.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of G3139 in combination with carboplatin and paclitaxel.
II. To determine the quantitative and qualitative nature of toxicities of G3139 with carboplatin and paclitaxel.
III. To measure G3139 activity in peripheral blood lymphocytes by quantitating Bcl-2/Bax expression and transcription, as well as T-cell functioning and signaling.
IV. To measure G3139 activity in tumor biopsy specimens by quantitating Bcl-2/Bax expression and transcription.
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 confirmed solid malignancy that is metastatic or unresectable and for which no standard curative therapy exists; patients with lymphoma are excluded
- •ECOG performance status 0, 1, or 2 (Karnofsky >= 60%)
- •Life expectancy of greater than 3 months
- •Leukocytes >= 3,000/mm^3
- •Absolute neutrophil count >= 1,500/mm^3
- •Platelets >= 100,000/mm^3
- •Total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
- •Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •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, for the duration of study participation, and for three months after discontinuation of treatment; 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
- •Patients will need to have a central line or nurse-placed PICC line in place prior to treatment on the protocol
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
- •Patients with known brain metastases will be excluded from this clinical trial
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to G3139 or other agents used in study, unless approved by investigator
- •No pre-existing grade >= 2 neuropathy
- •No personal history of a bleeding diathesis given potential significant antiplatelet effects of therapy
- •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 G3139
- •HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
研究组 & 干预措施
Treatment (oblimersen sodium, paclitaxel)
Patients receive oblimersen IV continuously on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
An additional cohort of 12-15 patients receives treatment as above with oblimersen at the MTD.
干预措施: oblimersen sodium (Biological)
Treatment (oblimersen sodium, paclitaxel)
Patients receive oblimersen IV continuously on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
An additional cohort of 12-15 patients receives treatment as above with oblimersen at the MTD.
干预措施: paclitaxel (Drug)
Treatment (oblimersen sodium, paclitaxel)
Patients receive oblimersen IV continuously on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
An additional cohort of 12-15 patients receives treatment as above with oblimersen at the MTD.
干预措施: laboratory biomarker analysis (Other)
Treatment (oblimersen sodium, paclitaxel)
Patients receive oblimersen IV continuously on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
An additional cohort of 12-15 patients receives treatment as above with oblimersen at the MTD.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum tolerated dose (MTD) defined as the highest safely tolerated dose where at most 1 patient experiences a dose-limiting toxicities (DLT) and the next higher dose having at least 2 patients who experience DLT
时间窗: 21 days
次要结局
- Pharmacokinetic parameters of G3139 in combination with paclitaxel and carboplatin(Day 1, 4, 5, and 6 of course 1)
- Disease response as having either progressive disease (PD), stable disease (SD), a partial response (PR), or a complete response (CR)(Up to 6 years)