Randomized Phase II Neoadjuvant Study of Temozolomide Alone or With Pegylated Interferon-alpha 2b in Patients With Resectable American Joint Committee on Cancer (AJCC) Stage IIIB/IIIC or Stage IV (M1a) Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Response to Neoadjuvant Therapy by Therapy Arms: Clinical Response Rates (CR + PR + SD)
研究概览
简要总结
The goal of this clinical research study is to learn if temozolomide alone or given with pegylated interferon alpha-2b can help to control metastatic melanoma. Researchers also want to study the safety of these 2 treatments.
Objectives:
- To determine the anti-tumor activity (pathological response CR+PR) and toxicity of temozolomide (TMZ) alone or in combination with pegylated interferon alpha-2b (PGI) in patients with resectable stage IIIC or stage IV (M1a) metastatic melanoma prior to definitive surgical resection.
- To determine the relapse-free survival, overall survival and the impact of tumor response to chemotherapy in these patients.
- To differentiate the in vivo treatment effects of TMZ alone vs.TMZ plus PGI and correlate with clinical outcome by analysis the pre- and post-treatment tumors and peripheral blood mononuclear cells with respect to:
- Known cellular and molecular markers of apoptosis and cell proliferation, 2) Promotor methylation status of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), 3) DNA sequence variability of tumor suppressor genes and DNA repair enzymes, 4) Tumor genomic expression profiles analysis by complementary DNA (cDNA) microarray and protein array
详细描述
Temozolomide is a drug that is designed to work by stopping cancer cells from making new DNA. If they cannot make DNA, they can't split into 2 new cancer cells.
Pegylated Interferon alpha-2b is a protein made by the human immune system that helps to fight viral infections and regulate cell function.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups (Arm A or Arm B). You have an equal chance of being assigned to either group and getting the treatment assigned to that group. You will not know which group you are assigned to.
Arm A: Participants in this group will take temozolomide once a day for 7 days in a row. This will be followed by 7 days without any treatment. This will be repeated 3 more times(for a total of 8 weeks - 1 cycle) before you have routine surgery.
Arm B: Participants in this group will take temozolomide on the same schedule as those in Arm A. However, participants in this group will also receive pegylated interferon alpha-2b as an injection under the skin once a week for a total of 8 weeks before they have routine surgery. Tylenol will be given to participants in this group before their pegylated interferon alpha-2b injection. After the first injection, they will also need to stay in the clinic for 2 hours of observation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
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 documented diagnosis of melanoma metastases.
- •Stage IIIB/IIIC (N2b, N2c and N3) or stage IV (M1a) melanoma patients with measurable and potentially resectable metastases without clinical and radiological evidence of other distant metastases.
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Age 18 or older.
- •Adequate organ function defined as follows: a.) Absolute granulocytes greater than or equal to 1,000/mm^3 and Platelets greater than or equal to 100,000/mm^3, b.) Serum bilirubin and serum creatinine of less than or equal to 1.5 times upper limit of laboratory normal. If serum creatinine is greater than 1.5 times upper limit of laboratory normal, the urine creatinine clearance must be greater than 60 ml/min., c.) serum glutamate oxaloacetate transaminase (SGOT) (AST), serum glutamate pyruvate transaminase (SGPT) (ALT) and alkaline phosphatase less than or equal to 3 times upper limit of laboratory normal.
- •Patients have not had any previous systemic chemotherapy for metastatic melanoma. Prior biologic therapy, targeted therapy or immunotherapy are allowable, but must be at least 2 weeks since prior therapy before starting study drugs. No other concurrent chemotherapy, immunotherapy, or radiotherapy.
- •Prior radiation therapy used to enhance local regional control is permitted, but must be at least 2 weeks since prior therapy before starting study drugs. In addition, the patient must have unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity. Lesions within the prior field of radiation may only be used as indicator lesions if there has been recent evidence of disease progression after .
- •Ability to understand and sign an informed consent form, indicating awareness of the investigational nature of this study.
排除标准
- •Significant cardiac or pulmonary dysfunction, such as a history of severe cardiovascular disease, myocardial infarction within 6 months of the start of treatment, unstable angina, Class III or Class IV congestive heart failure, ventricular arrhythmia, or any uncontrolled arrhythmia.
- •Current significant psychiatric illness.
- •Serious infection requiring intravenous antibiotics, or any non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by complications of this therapy.
- •Frequent vomiting or any medical condition (e.g. partial bowel obstruction) that could interfere with oral medication intake.
- •Autoimmune or immunosuppressive disorders (e.g. HIV or AIDS-related illness).
- •Patients who require therapy with systemic corticosteroids.
- •No evidence of active secondary malignancy that requires chemotherapy within the past 2 years (excluding non-melanoma skin cancer, and/or all carcinoma in-situ)
- •Pregnant or lactating women are ineligible. Women of childbearing potential must have a negative urine pregnancy test within a week of initiation of therapy. All patients must agree to use medically approved contraceptive measures to prevent pregnancy during treatment.
- •Any other medical condition or reason that, in the principal investigator's opinion, makes the patient unsuitable to participate in a clinical trial.
研究组 & 干预措施
Temozolomide (TMZ) + Pegylated Interferon-alpha 2b (PGI)
Temozolomide = TMZ and PGI = Pegylated Interferon-alpha 2b
Temozolomide 150 mg/m^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks. Pegylated Interferon-alpha 2b 0.5 mcg/kg subcutaneous injection once weekly for a total of 8 weeks.
干预措施: Pegylated Interferon Alpha-2b (PGI) (Drug)
Temozolomide (TMZ) + Pegylated Interferon-alpha 2b (PGI)
Temozolomide = TMZ and PGI = Pegylated Interferon-alpha 2b
Temozolomide 150 mg/m^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks. Pegylated Interferon-alpha 2b 0.5 mcg/kg subcutaneous injection once weekly for a total of 8 weeks.
干预措施: Temozolomide (TMZ) (Drug)
Temozolomide (TMZ)
Temozolomide = TMZ - 150 mg/m^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks.
干预措施: Temozolomide (TMZ) (Drug)
结局指标
主要结局
Response to Neoadjuvant Therapy by Therapy Arms: Clinical Response Rates (CR + PR + SD)
时间窗: Evaluated after a total of 8 weeks of therapy before definitive surgery.
Response to neoadjuvant therapy reported as number of participants with clinical response, defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD). Clinical Complete Response (CR): Disappearance of all clinical evidence of visible tumor. Partial Response (PR) : 30% or \> decrease in the sum of the of the longest diameter of target lesions, taking as reference the baseline sum longest diameter persisting for at least 4 weeks. Progressive Disease (PD): \> 20% increase in sum of longest diameter of target lesions, reference baseline sum longest diameter. Appearance new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, reference smallest sum longest diameter since treatment started.
Response to Neoadjuvant Therapy: Overall Clinical Responses
时间窗: Evaluated after a total of 8 weeks of therapy before definitive surgery.
Response to neoadjuvant therapy reported as number of participants with clinical response, defined as Clinical Complete Response (CR): Disappearance of all clinical evidence of visible tumor. Partial Response (PR) : 30% or \> decrease in the sum of the of the longest diameter of target lesions, taking as reference the baseline sum longest diameter persisting for at least 4 weeks. Progressive Disease (PD): \> 20% increase in sum of longest diameter of target lesions, reference baseline sum longest diameter. Appearance new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, reference smallest sum longest diameter since treatment started.
次要结局
未报告次要终点