A Parallel Phase I/II Study of Low Dose Decitabine (5-Aza-Deoxycytidine) With Peginterferon Alfa-2b in Advanced Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Phase I: Dose-limiting toxicity (DLT)
研究概览
简要总结
The goal of the first phase of this clinical research study is to find the highest tolerable dose of decitabine and peginterferon alfa-2b that can be given in combination to patients with melanoma. The safety of this drug combination will also be studied.
The goals of the second phase are to learn if decitabine and peginterferon alfa-2b combined can help to control melanoma, and to find out which doses are more effective and/or better tolerated.
详细描述
The Study Drugs:
Decitabine is designed to damage the DNA of cells, which may cause cancer cells to die.
Peginterferon alfa-2b is designed to strengthen the immune system, which may decrease tumor growth.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 6 groups of 3-6 participants will be enrolled in the Phase I portion of the study, and up to 44 participants will be enrolled in Phase II.
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 pathologically confirmed malignant melanoma that is unresectable stage III or stage IV.
- •Patients must have measurable disease as defined by RECIST criteria.
- •No more than two prior chemotherapy for unresectable stage III or IV melanoma.
- •Patients must be >/= 28 days beyond the last administration of anticancer therapy, and must have recovered from the toxicities of prior therapy. If the patient was recently treated with a nitrosurea, they must be >/= 42 days beyond the last administration.
- •Patients must have no other active malignancies. Patients with prior history of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark I melanoma in situ or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible, if their disease has been inactive for 2 years prior to the time of study entry.
- •Patients must be >/= 18 years of age.
- •Patients must give written informed consent prior to initiation of therapy in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of this study and the risks associated with the therapy.
- •Women of childbearing potential (WOCBP) must not be pregnant (negative urine human chorionic gonadotropin (HCG) within 2 weeks of treatment) or lactating. A WOCBP is defined as a woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months.
- •Women of childbearing potential and sexually active males must be counseled to use an accepted and effective method of contraception (including abstinence) while on treatment and for a period of 3 months after completing or discontinuing treatment.
- •Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Patients must have adequate organ and marrow function, measured within 14 days of study entry, as defined below: All Patients: - Absolute neutrophil count >/=1,500/uL - Platelets >/=100,000/uL - Creatinine (serum) </= 2.0 mg/dL - Total bilirubin </= 1.5 mg/dL - AST(SGOT)/ALT(SGPT) </= 2.5 X Institutional Upper Limit of Normal (IULN)
- •Patients with any number of prior targeted or cytokine therapies, but no more than two chemotherapy containing regimens.
排除标准
- •Patients with active autoimmune disorders or who are receiving immunosuppressive therapy (including steroids or methotrexate) for any indication are excluded. An exception may be made, by the PI, to include patients with adrenal insufficiency requiring physiologic steroid hormone replacement only.
- •Patients who have previously received adjuvant high dose interferon.
- •Patients may not receive any other investigational agents within four weeks of study entry. Patients may not receive any other investigational agents while on study.
- •Patients who have had major surgery within 2 weeks prior to entering the study, or have otherwise not adequately recovered from prior surgery.
- •Patients who have had palliative radiation therapy within 2 weeks prior to entering the study.
- •Patients with brain metastases.
- •Patients with a history of active ischemic heart disease or cerebro-vascular disease, congestive heart failure (NYHA class >2) or anginal syndrome requiring ongoing medical treatment.
- •Patients with myocardial ischemia (MI), stroke, or transient ischemic attack (TIA) within the last 6 months.
- •Patients with a diagnosis or evidence of organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that might preclude participation in the protocol.
- •Patients with a history of central nervous system (CNS) demyelinating, inflammatory disease or hereditary or acquired peripheral neuropathy.
- •Patients with known history of HIV and hepatitis infection or any other significant medical or surgical condition or psychiatric disorder that may interfere with the completion of this trial or with the evaluation of safety and efficacy of the study combination.
- •Patients with thyroid dysfunction not responsive to therapy.
研究组 & 干预措施
Decitabine + Peginterferon Alfa-2b
Decitabine starting dose of 10mg/m^2 given daily via intravenous infusion on days 1-5 of 28 day cycle. Peginterferon Alfa-2b starting dose of 3 µg/kg injection under the skin once a week on days 1, 8, 15, and 21 of 28 day cycle.
干预措施: Decitabine (Drug)
Decitabine + Peginterferon Alfa-2b
Decitabine starting dose of 10mg/m^2 given daily via intravenous infusion on days 1-5 of 28 day cycle. Peginterferon Alfa-2b starting dose of 3 µg/kg injection under the skin once a week on days 1, 8, 15, and 21 of 28 day cycle.
干预措施: Pegylated Interferon Alpha-2b (Drug)
结局指标
主要结局
Phase I: Dose-limiting toxicity (DLT)
时间窗: 4 weeks
Dose limiting toxicity defined as any treatment related toxicity that meets one or more of the following criteria: Any grade 3 or 4 non-hematologic toxicity regardless of duration, except: 1. Grade 3 nausea or vomiting occurring without maximal antiemetic therapy. 2. Grade 3 diarrhea that occurs following without adequate loperamide therapy. * Grade 4 thrombocytopenia. * Grade 4 neutropenia lasting \> 2 weeks or associated with infection. * Any toxicity that results in a treatment delay of \> 4weeks.
次要结局
- Phase II: Patient Response(12 weeks)