A Phase I/2 Study of GTI-2040 Combined With Docetaxel In Metastatic Or Unresectable Locally Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of patients experiencing dose limiting toxicities (DLTs), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 (Phase I)
研究概览
简要总结
Phase I/II trial to study the effectiveness of combining GTI-2040 with docetaxel in treating patients who have recurrent, metastatic, or unresectable locally advanced non-small cell lung cancer, prostate cancer, or other solid tumors. GTI-2040 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of docetaxel by making the tumor cells more sensitive to the drug. Combining GTI-2040 with docetaxel may kill more tumor cells
详细描述
OBJECTIVES:
I. Determine the recommended phase II dose of GTI-2040 and docetaxel in patients with recurrent, metastatic, or unresectable locally advanced non-small cell lung cancer, prostate cancer, or other solid tumors (phase I study closed to accrual as of 8/5/2004).
II. Determine the toxicity of this regimen in these patients. III. Determine the objective tumor response rate in patients treated with this regimen.
IV. Determine the stable disease rate, time to disease progression, objective response duration, and duration of stable disease in patients treated with this regimen.
V. Determine the pharmacokinetics of GTI-2040 when administered in combination with docetaxel 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 diagnosis of 1 of the following:
- •Solid tumor malignancy (phase I only)*
- •Prostate cancer (phase I only)*
- •Non-small cell lung cancer (phase I and II)*
- •Recurrent, metastatic, locally advanced unresectable, or treatment-refractory disease
- •Measurable disease
- •At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
- •Previously irradiated lesions are considered measurable provided they have demonstrated progression before study entry
- •No bone-only disease
- •Must have measurable disease other than bone lesions
- •No stage IIIA or IIIB non-small cell lung cancer without a malignant pleural or pericardial effusion that is eligible for first-line radical combined chemotherapy and radiotherapy
- •No known progressive or symptomatic brain metastases
- •Asymptomatic brain metastases allowed
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •More than 3 months
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •No history of coagulopathy
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- •AST/ALT no greater than 2 times ULN (3.5 times ULN if liver metastases are present)
- •INR no greater than 1.3
- •APTT no greater than 1.25 times ULN
- •Creatinine no greater than 1.5 times ULN
- •Creatinine clearance at least 50 mL/min
- •No symptomatic congestive heart failure
- •No evidence of cardiac dysfunction
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No active peptic ulcer disease
- •No poorly controlled diabetes mellitus
- •No pre-existing grade 2 or greater neuropathy
- •No ongoing or active infection
- •No contraindication to corticosteroids
- •No psychiatric illness or social situation that would limit compliance with study requirements
- •No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs
- •No other concurrent uncontrolled illness
- •One, and only one, prior chemotherapy regimen for advanced disease (not including adjuvant therapy) allowed
- •Neoadjuvant/adjuvant chemotherapy allowed
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
- •Prior multiple lines of endocrine therapy for advanced solid tumors allowed
- •More than 4 weeks since prior endocrine therapy and recovered
- •Concurrent steroids allowed
- •See Disease Characteristics
- •More than 4 weeks since prior radiotherapy and recovered
- •No concurrent radiotherapy to sole site of measurable disease
- 另有 6 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (GTI-2040, docetaxel)
Phase I (closed to accrual as of 8/5/2004): Patients receive GTI-2040 IV continuously on days 1-14. Patients also receive docetaxel IV over 1 hour on day 3 during course 1 and on day 1 for all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of GTI-2040 and docetaxel until the MTD is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The RP2D is defined as the dose preceding the MTD.
Phase II: Patients receive GTI-2040 and docetaxel at the RP2D as in phase I.
干预措施: GTI-2040 (Biological)
Treatment (GTI-2040, docetaxel)
Phase I (closed to accrual as of 8/5/2004): Patients receive GTI-2040 IV continuously on days 1-14. Patients also receive docetaxel IV over 1 hour on day 3 during course 1 and on day 1 for all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of GTI-2040 and docetaxel until the MTD is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The RP2D is defined as the dose preceding the MTD.
Phase II: Patients receive GTI-2040 and docetaxel at the RP2D as in phase I.
干预措施: docetaxel (Drug)
Treatment (GTI-2040, docetaxel)
Phase I (closed to accrual as of 8/5/2004): Patients receive GTI-2040 IV continuously on days 1-14. Patients also receive docetaxel IV over 1 hour on day 3 during course 1 and on day 1 for all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of GTI-2040 and docetaxel until the MTD is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The RP2D is defined as the dose preceding the MTD.
Phase II: Patients receive GTI-2040 and docetaxel at the RP2D as in phase I.
干预措施: laboratory biomarker analysis (Other)
Treatment (GTI-2040, docetaxel)
Phase I (closed to accrual as of 8/5/2004): Patients receive GTI-2040 IV continuously on days 1-14. Patients also receive docetaxel IV over 1 hour on day 3 during course 1 and on day 1 for all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of GTI-2040 and docetaxel until the MTD is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The RP2D is defined as the dose preceding the MTD.
Phase II: Patients receive GTI-2040 and docetaxel at the RP2D as in phase I.
干预措施: pharmacological study (Other)
结局指标
主要结局
Number of patients experiencing dose limiting toxicities (DLTs), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 (Phase I)
时间窗: Up to day 21
Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II)
时间窗: Up to day 42
The 95% confidence intervals will be provided.
次要结局
- Stable disease rate(Up to 6 weeks)
- Response duration(Up to 4 years)
- Toxicities of GTI-2040 combined with docetaxel, graded according to the NCI CTC v2.0(Up to 4 years)
- Time to disease progression(Up to 4 years)
- Duration of stable disease(Up to 6 weeks)
- Level of ribonucleotide reductase (RNR) activity(Up to week 10)
- Tumoral expression in terms of c-myc, R2 subunit protein levels and markers of proliferation (cyclin B1) and apoptosis (activated caspase 3)(Up to week 10)