Pilot Study to Test the Safety and Efficacy of the Combination of Imiquimod and Pembrolizumab for the Treatment of Metastatic Melanoma
概览
- 阶段
- 早期 1 期
- 干预措施
- Imiquimod
- 疾病 / 适应症
- 未指定
- 发起方
- Mayo Clinic
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Progression Free Survival
- 状态
- 已完成
- 最后更新
- 上个月
概览
简要总结
This pilot early phase I trial studies the side effects and how well imiquimod and pembrolizumab work in treating patients with stage IIIB-IV melanoma. Imiquimod may stimulate the immune system. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving imiquimod and pembrolizumab may work better at treating melanoma.
详细描述
PRIMARY OBJECTIVES: I. To gain preliminary data of the anti-tumor activity and safety profile of the combination of imiquimod and pembrolizumab in patients with unresectable cutaneous melanoma. CORRELATIVE RESEARCH OBJECTIVES: I. To compare and contrast (in a hypothesis generating manner) the biomarker profiles of patients who have a confirmed complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with patients who do not. OUTLINE: Patients receive pembrolizumab intravenously (IV) on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Cycles repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline, 6 weeks, and 12 weeks and computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) throughout the trial. After completion of study treatment, patients are followed up every 12 weeks for 1 year and then every 6 months for up to 3 years after registration.
研究者
入排标准
入选标准
- •Histological confirmation of stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c that is not suitable for surgical resection
- •Patients must not have received prior pembrolizumab or other anti-PD1/PDL1 therapies for their metastatic disease
- •At least one cutaneous lesion that is amenable to treatment with topical imiquimod
- •Measurable disease by RECIST
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- •Absolute neutrophil count (ANC) \>= 1500/mm\^3
- •Platelet count \>= 100,000/mm\^3
- •Hemoglobin \> 9.0 g/dL or \>= 5.6 mmol/L without transfusion or (EPO) erythropoietin dependency (within 7 days of assessment)
- •Serum total bilirubin =\< 1.5 X upper limit of normal (ULN) or direct bilirubin =\< (ULN) for subjects with total bilirubin levels \> 1.5 ULN
- •Aspartate transaminase (AST) =\< 2.5 x ULN or =\< 5 x ULN for subjects with liver metastases
排除标准
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •NOTE: female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year; male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy; abstain from heterosexual activity is also acceptable method of contraception for males
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm or used an investigational device =\< 4 weeks from registration
- •History of myocardial infarction =\< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
研究组 & 干预措施
Treatment (pembrolizumab, imiquimod)
Patients receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Cycles repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline, 6 weeks, and 12 weeks and CT, PET/CT, or MRI throughout the trial.
干预措施: Imiquimod
Treatment (pembrolizumab, imiquimod)
Patients receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Cycles repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline, 6 weeks, and 12 weeks and CT, PET/CT, or MRI throughout the trial.
干预措施: Biopsy
Treatment (pembrolizumab, imiquimod)
Patients receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Cycles repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline, 6 weeks, and 12 weeks and CT, PET/CT, or MRI throughout the trial.
干预措施: Pembrolizumab
Treatment (pembrolizumab, imiquimod)
Patients receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Cycles repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline, 6 weeks, and 12 weeks and CT, PET/CT, or MRI throughout the trial.
干预措施: Computed Tomography
Treatment (pembrolizumab, imiquimod)
Patients receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Cycles repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline, 6 weeks, and 12 weeks and CT, PET/CT, or MRI throughout the trial.
干预措施: Positron Emission Tomography
Treatment (pembrolizumab, imiquimod)
Patients receive pembrolizumab IV on day 1 and apply imiquimod cutaneously on days 1-5 (Monday - Friday). Cycles repeat every 21 days for up to 2 years (approximately 35 courses) in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline, 6 weeks, and 12 weeks and CT, PET/CT, or MRI throughout the trial.
干预措施: Magnetic Resonance Imaging
结局指标
主要结局
Progression Free Survival
时间窗: 7 months
Defined as the time from registration to documentation of first disease progression or death due to any cause. Will be estimated using the Kaplan-Meier method. The 7 month PFS rate was calculated.
Duration of Response
时间窗: 16 months
Defined as the time from response to disease progression.
Incidence of Adverse Events (AEs)
时间窗: 16 months
AEs are graded using Common Terminology Criteria for Adverse Events version 4.0
Overall Survival
时间窗: 21 months
Defined as the time from registration to death due to any cause. Will be estimated using the Kaplan-Meier method. The 21 month OS rate was calculated here.
Tumor Response Rate
时间窗: 16 months
Defined as percentage of patients whose objective disease status meets the criteria for Response Evaluation Criteria in Solid Tumors (RECIST) criteria for partial or complete response on two consecutive disease evaluations.