Phase II Study Incorporating Pegylated Interferon In the Treatment For Children With High-Risk Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 29
- 试验地点
- 6
- 主要终点
- Probability of Event-free Survival (EFS) of Stratum A Participants
研究概览
简要总结
The main goal of this study is to estimate the tumor response rate of temozolomide administered in combination with peginterferon alfa-2b to pediatric patients with unresectable Stage III, metastatic, or recurrent cutaneous melanoma.
详细描述
This study is for children with malignant melanoma and high risk features (at high risk of melanoma returning or spreading to other parts of the body) or who have recurrent disease. The study has two treatment groups based on the stage of the disease. Patients with stage IIC, IIIA or IIIB melanoma whose tumors have been removed by surgery will be treated in study group A. These patients will receive 4 weeks of high dose interferon alfa-2b followed by 48 weeks of peginterferon. Patients with stage IIIC or IV melanoma, stage III melanoma that could not be removed by surgery and those with recurrent disease will be treated in study group B. These patients will receive peginterferon alfa-2b and temozolomide.
Stratum A: Resected Stages IIC, IIIA, and IIIB patients
Induction therapy (weeks 1-4): Subjects will receive recombinant interferon alfa-2b 20 million units/m2 per day intravenously over 20-30 minutes on 5 consecutive days per week for 4 weeks. Subjects will receive peginterferon alfa-2b 1 mcg/kg/week subcutaneously for a total of 48 weeks.
Stratum B: Resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent patients
Stratum B is divided into 2 groups based on the presence (Stratum B1) or absence (Stratum B2) of measurable disease. Subjects will receive 8 weekly doses of peginterferon alfa-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75mg/m2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course will be 8 weeks. Strata B2 (no measurable disease) will proceed with 7 courses as outlined.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •AJCC stage IIC, III, IV or recurrent cutaneous melanoma
- •Adequate bone marrow function
- •Age less than or equal to 21 years of age at diagnosis
- •Adequate liver and kidney function
排除标准
- •Prior Therapy with dacarbazine or temozolomide
- •Patients who have uncontrolled infection
- •Patients with autoimmune hepatitis
- •Patients who have a history of depression or other psychiatric diseases requiring hospitalization
- •Patients taking systemic corticosteroids including oral steroids (i.e. prednisone, dexamethasone) or topical steroid creams/ointments. Steroid containing inhalers, steroid replacement for adrenal insufficiency and steroid premedication for prevention of transfusion or imaging contrast-agent related allergic reaction will be permitted.
- •Patients with hypersensitivity reaction to non-pegylated interferon α-2b are not eligible for study
- •Patients with diabetes mellitus not adequately controlled with medication
- •Patients with hypo- or hyperthyroidism not adequately controlled with medication.
- •Patients with a history of myocardial infarction, severe or unstable angina, or severe peripheral vascular disease.
研究组 & 干预措施
Peginterferon alfa-2b/non-pegylated interferon alfa-2b
Stratum A: Resected Stages IIC, IIIA, and IIIB patients will receive recombinant interferon alfa-2b 20 million units/m2/day intravenously (IV) 5 consecutive days per week for 4 weeks followed by peginterferon alfa-2b 1mcg/kg subcutaneously (SQ) once a week for 48 weeks.
干预措施: Recombinant interferon alfa-2b (Drug)
Temozolomide/peginterferon alfa-2b
Stratum B: Resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent patients
Stratum B is divided into 2 groups based on the presence (Stratum B1) or absence (Stratum B2) of measurable disease. Subjects will receive 8 weekly doses of peginterferon alfa-2b 0.5 mcg/kg/dose subcutaneously (SQ) in combination with temozolomide 75mg/m2/dose by mouth (PO) daily for 6 weeks followed by 2 week break. The duration of each treatment course will be 8 weeks. Strata B2 (no measurable disease) will proceed with 7 courses as outlined.
干预措施: Peginterferon alfa-2b (Drug)
Temozolomide/peginterferon alfa-2b
Stratum B: Resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent patients
Stratum B is divided into 2 groups based on the presence (Stratum B1) or absence (Stratum B2) of measurable disease. Subjects will receive 8 weekly doses of peginterferon alfa-2b 0.5 mcg/kg/dose subcutaneously (SQ) in combination with temozolomide 75mg/m2/dose by mouth (PO) daily for 6 weeks followed by 2 week break. The duration of each treatment course will be 8 weeks. Strata B2 (no measurable disease) will proceed with 7 courses as outlined.
干预措施: Temozolomide (Drug)
Peginterferon alfa-2b/non-pegylated interferon alfa-2b
Stratum A: Resected Stages IIC, IIIA, and IIIB patients will receive recombinant interferon alfa-2b 20 million units/m2/day intravenously (IV) 5 consecutive days per week for 4 weeks followed by peginterferon alfa-2b 1mcg/kg subcutaneously (SQ) once a week for 48 weeks.
干预措施: Temozolomide (Drug)
Peginterferon alfa-2b/non-pegylated interferon alfa-2b
Stratum A: Resected Stages IIC, IIIA, and IIIB patients will receive recombinant interferon alfa-2b 20 million units/m2/day intravenously (IV) 5 consecutive days per week for 4 weeks followed by peginterferon alfa-2b 1mcg/kg subcutaneously (SQ) once a week for 48 weeks.
干预措施: Peginterferon alfa-2b (Drug)
结局指标
主要结局
Probability of Event-free Survival (EFS) of Stratum A Participants
时间窗: 3 years from diagnosis
The probability of EFS was estimated as time to first event (relapse, death or second malignancy). As of April 2016, 21 out of 23 participants had no events. The EFS rate was estimated by Kaplan-Meier method.
Tumor Response Rate
时间窗: 8 weeks
Tumor response rate of stratum B1 participants was evaluated after 1 treatment course of temozolomide plus peginterferon ɑ-2b. Complete response (CR) and partial response (PR) confirmed with repeated scan at least 4 weeks apart following completion of course 1 therapy. CR defined as disappearance of all target and non-target lesions with no new lesions detected. If available, no disease must be detected by immunocytology or serum tumor markers. PR defined as at least 30% decrease in disease measurement compared to disease measurement at study entry with no new lesions detected. Progressive disease (PD) defined as at least 20% increase in the disease measurement compared to the smallest disease measurement recorded since start of treatment, or appearance of one or more new lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD compared to smallest disease measurement since start of treatment.
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Strata B1 and B2
时间窗: 52 weeks
The objective was to assess the safety of temozolomide administered in combination with peginterferon a-2b in Stratum B participants. Accrual was suspended any time during therapy if 2 or more of 6, 4 or more of 12, 6 or more of 18, 8 or more of 24, 10 or more of 30 participants experienced target toxicity defined as: * Grade 4 non-hematologic (non-hem) toxicity that does not resolve to ≤grade 1 within 2 weeks from the time next dose is due and is determined to be probably or definitely related to protocol therapy * Grade 4 non-hem toxicity that is NOT constitutional symptoms (fever, chills, fatigue and/or pain) * Grade 3 elevations in creatinine or BUN that are determined to be probably or definitely related to protocol therapy * Grade 4 cardiopulmonary toxicity that is determined to be probably or definitely related to protocol therapy * Grade 4 mood alteration (suicidal ideation; danger to self or others)
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients
时间窗: 52 weeks
The objective was to study the feasibility and safety of administering peginterferon a-2b weekly for 48 weeks following the initial induction phase to Stratum A participants. Accrual was suspended during the 48-week course if 2 or more of 6, 4 or more of 12, 6 or more of 18, 8 or more of 24, 10 or more of 30 participants experienced target toxicity defined as: * Grade 4 non-hematologic (non-hem) toxicity that does not resolve to ≤grade 1 within 2 weeks from the time next dose is due and is determined to be probably or definitely related to protocol therapy * Grade 4 non-hem toxicity that is NOT constitutional symptoms (fever, chills, fatigue and/or pain) * Grade 3 elevations in creatinine or BUN that are determined to be probably or definitely related to protocol therapy * Grade 4 cardiopulmonary toxicity that is determined to be probably or definitely related to protocol therapy * Grade 4 mood alteration (suicidal ideation; danger to self or others)
次要结局
未报告次要终点