A Phase I, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sodium Stibogluconate in Combination With Interferon Alpha-2b for Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD) of SSG in combination with IFN alpha2b
研究概览
简要总结
Primary Objective:
-To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of SSG in combination with IFN alpha2b in patients with advanced malignancies.
Secondary Objectives:
- To correlate the AUC of SSG with clinical toxicity and efficacy.
- To quantify the effect of SSG on IFN alpha2b induced gene modulation and signal transduction pathways.
- To characterize the effects of SSG on PTPases SHP-1 and SHP-2.
- To assess the safety, efficacy, and PK of SSG in combination with IFN alpha2b.
详细描述
Sodium stibogluconate is a drug that is able to block an enzyme in the cells that is responsible for cell growth. By blocking this enzyme, it may be able to prevent cancer cells from multiplying.
Interferon alfa-2b is a drug that activates an immune response to infections in the body. By triggering an immune response, this drug may help to prevent some cancer cells from growing and multiplying. You will receive treatment with both sodium stibogluconate and interferon alfa-2b, because sodium stibogluconate may improve the effectiveness of interferon in treating the cancer.
Participants will be enrolled in groups of 3 on this study, and the doses of the study drugs will be escalated for each group. This means that each new group of 3 participants will get a higher dose of the study drugs than the group before them. This will continue until the highest tolerable dose combination is found.
Once the highest tolerable dose has been found, up to an additional 9 participants, called the expansion group, will receive study drug at that dose. Your doctor will tell you if you are in the expansion group.
If you are found to be eligible to take part in this study, you will go to the clinic to start treatment. During Cycle 1, you will be given sodium stibogluconate once a day by vein during Days 1-5. On Days 8-12, you will be given sodium stibogluconate once a day by vein, and you will be given interferon alfa-2b for 3 days by injection just under the skin on Days 8, 10, and 12. For every cycle after Cycle 1, you will be given sodium stibogluconate once a day by vein during Days 1-5 and 8-12, and you will be given interferon alfa-2b for 3 days by injection just under the skin on Days 1, 3,5, 8, 10, and 12. Treatment cycles will last about 3 weeks (2 weeks on treatment, followed by 1 week off treatment).
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 who sign a written informed consent document and are able to comply with the study protocol for the duration of the study.
- •Patients who have a histologically or cytologically confirmed diagnosis malignancy (patients with measurable or non-measurable disease) who have progressed following effective therapy or for which no effective therapy exists.
- •Patients who are greater than or equal to 18 years of age.
- •Patients who have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-
- •Patients who have an estimated life expectancy of 3 months.
- •Patients who have a normal cardiac ejection fraction, >50% estimated by 2 D Echocardiogram or MUGA.
- •Patients who have adequate organ function as indicated by the following laboratory values obtained within 10 days prior to the first dose of SSG: Granulocytes>/=1,500 microliter, Platelets>/= 100,000 microliter, Hemoglobin >/=9.0 g/dL,Creatinine (Cr) </= 1.5 mg/dL, Bilirubin Normal limits, or <2.0 x ULN with liver metastases, Aspartate aminotransferase (AST) <2.5 * ULN or <5.0 * ULN with liver metastases, Alanine aminotransferase (ALT)<2.5 * ULN or <5.0 * ULN with liver metastases.
排除标准
- •Patients on concurrent immunotherapy, including IFN therapy (prior therapy is allowed if >/= 4 months since immunotherapy).
- •Patients who have received investigational drugs including immunotherapy, gene therapy, hormone therapy, biologic therapy, radiation therapy, chemotherapy, or had major surgery within 3 weeks of study enrollment
- •Patients who have not recovered from acute toxicity of previous therapy prior to enrollment.
- •Patients with medically uncontrolled cardiovascular illness, unstable angina, congestive heart failure, history of myocardial infarction, electrocardiogram (ECG) abnormalities suggestive of cardiac conduction delay (QTc >0.47 seconds), history of atrial fibrillation or flutter, or other serious clinically significant cardiac arrhythmia
- •Patients who have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant.
- •Pregnant or lactating women, and fertile women or men unless surgically sterile or using effective contraception; All female patients of childbearing potential or < 1 year postmenopausal must have a negative beta human chorionic gonadotropin (βhCG) pregnancy test at baseline and be practicing a medically acceptable method of birth control (oral contraceptives for at least 3 months, implantation of an intrauterine device at least 2 months, or barrier methods [e.g. vaginal diaphragm, vaginal sponge, or condom with spermicidal jelly]). These must be continued for 3 months after study initiation
- •Patients who use daily glucocorticoids except for physiological replacement.
- •Patients who are known to be positive for Hepatitis B surface antigen, Hepatitis C or human immunodeficiency virus (HIV).
- •Patients with prior history of solid organ allografts or allogeneic bone marrow transplant.
- •Patients who have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up.
- •Patients who have any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- •Patient who have symptomatic or untreated central nervous system metastases.
- •Patients taking the following medications will not be eligible: Amiodarone (Cordarone); Disopyramide (Norpace); Dofetilide (Tikosyn); Procainamide (Procanbid, Pronestyl); Quinidine (Quinaglute); Sotalol (Betapace); Erythromycin; Azithromycin (Z-pack), cont'd
- •Clarithromycin (Biaxin); Pentamidine (Pentacarinat); Trimethoprim-sulfamethoxazole (Bactrim); Bepridil (Vascor); Phenothiazines-prochlorperazine (Compazine), promethazine (Phenergan), chlorpromazine (Thorazine) or any antipsychotic medication; Butyrophenones-Haloperidol (Haldol), cont'd
- •Risperidone (Risperdal); Tricyclic or tetracyclic antidepressants-imipramine (Tofranil), amitriptyline (Elavil), desipramine (Norpramin), nortriptyline (Pamelor); Monoamine oxidase inhibitors; High dose methadone; Arsenic trioxide; Dolasetron (Anzemet); Any herbal preparations; or • Chronic need for colony stimulating factors (i.e., GM-CSF), erythropoietin use is permitted.
- •Patients with a history of hypersensitivity to IFN a-2b or SSG or any of their components.
研究组 & 干预措施
SSG + Intron A
Sodium Stibogluconate (SSG) 400 mg/m^2 intravenous (IV) daily on days 1-5 + Interferon Alfa-2b (Intron A) 3x10^6 units subcutaneously three times weekly
干预措施: Sodium Stibogluconate (Drug)
SSG + Intron A
Sodium Stibogluconate (SSG) 400 mg/m^2 intravenous (IV) daily on days 1-5 + Interferon Alfa-2b (Intron A) 3x10^6 units subcutaneously three times weekly
干预措施: Interferon Alpha-2b (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of SSG in combination with IFN alpha2b
时间窗: Continuous assessment with each 3 week cycle
MTD defined as the highest dose at which no dose limiting toxicity (DLT) occurs.
次要结局
未报告次要终点