A Phase I Trial Of G3139 (BCL-2 Antisense, NSC# 683428, IND# 58842) Combined With Cytotoxic Chemotherapy In Relapsed Childhood Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Dose-limiting toxic effects and recommended phase II dose, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
研究概览
简要总结
Phase I trial to study the effectiveness of oblimersen plus combination chemotherapy and dexrazoxane in treating children and adolescents who have relapsed or refractory 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 doxorubicin and cyclophosphamide by making the tumor cells more sensitive to the drug. Chemoprotective drugs such as dexrazoxane may protect normal cells from the side effects of chemotherapy
详细描述
OBJECTIVES:
I. Determine the dose-limiting toxic effects and recommended phase II dose of oblimersen when combined with cyclophosphamide, doxorubicin, and dexrazoxane in pediatric patients with relapsed or refractory solid tumors.
II. Determine the pharmacokinetic behavior of this regimen in these patients. III. Determine, preliminarily, the antitumor activity of oblimersen in these patients.
IV. Assess the biologic activity of oblimersen in mononuclear cells and tumor tissues, in terms of bcl-2 and related protein expression, in these patients.
OUTLINE: This is a 2-part, multicenter, 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
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed solid tumor at original diagnosis that has failed standard therapy or for which no standard therapy exists
- •Patients must have a disease for which there is no known curative potential
- •Patients must meet the following criteria for bone marrow function:
- •Status post stem cell transplantation (SCT)
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3 (transfusion independent)
- •Hemoglobin at least 8.0 g/dL (RBC transfusions allowed)
- •No lymphomas
- •No CNS tumors or known metastatic disease to the brain or spinal cord
- •Performance status - Karnofsky 50-100% (age 11 to 21)
- •Performance status - Lansky 50-100% (age 1 to 10)
- •At least 8 weeks
- •See Disease Characteristics
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- •ALT no greater than 3 times ULN
- •No significant hepatic dysfunction
- •Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
- •Creatinine, based on age, as follows:
- •Age 1 to 5: no greater than 0.8 mg/dL
- •Age 6 to 10: no greater than 1.0 mg/dL
- •Age 11 to 15: no greater than 1.2 mg/dL
- •Age 16 to 21: no greater than 1.5 mg/dL
- •No significant renal dysfunction
- •Shortening fraction at least 28% by echocardiogram
- •Ejection fraction at least 45% by MUGA
- •No significant pulmonary dysfunction
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No serious uncontrolled infections
- •No other end-organ dysfunction that would preclude study entry
- •No other clinically significant systemic illness
- •See Disease Characteristics
- •Recovered from prior immunotherapy
- •At least 1 week since prior growth factors or other biologic agents
- •At least 6 months since prior autologous SCT
- •At least 6 months since prior allogeneic bone marrow transplantation and recovered with no evidence of graft-versus-host disease
- •No concurrent immunomodulating agents
- •No concurrent prophylactic growth factors during the first course of the study
- •No concurrent immunotherapy or other biologic therapy
- •Recovered from prior chemotherapy
- •At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
- •No prior life-time cumulative doxorubicin dose of more than 450 mg/m^2 or equivalent
- •No other concurrent chemotherapy
- •Concurrent chronic steroids allowed
- •Recovered from prior radiotherapy
- •More than 2 weeks since prior localized palliative radiotherapy (small port)
- •More than 6 months since prior substantial radiotherapy to bone marrow (craniospinal radiotherapy, total body irradiation, or hemi-pelvic radiotherapy)
- •No concurrent radiotherapy
- •Concurrent chronic medications (e.g., narcotics or antiepileptics) allowed
- 另有 2 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
干预措施: oblimersen sodium (Biological)
Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
干预措施: dexrazoxane hydrochloride (Drug)
Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
干预措施: doxorubicin hydrochloride (Drug)
Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
干预措施: cyclophosphamide (Drug)
Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
干预措施: filgrastim (Biological)
Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
干预措施: laboratory biomarker analysis (Other)
Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
干预措施: pharmacological study (Other)
结局指标
主要结局
Dose-limiting toxic effects and recommended phase II dose, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
时间窗: Up to day 21
Change in pharmacokinetic behavior of this regimen
时间窗: Days 1 (pre-infusion), 5, 6, and 8 (end of infusion)
Antitumor activity
时间窗: Up to day 21
Biologic activity of oblimersen in mononuclear cells and tumor tissues, in terms of B-cell lymphoma 2 (bcl-2) and related protein expression
时间窗: Up to day 21
次要结局
未报告次要终点