Phase II Study of Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- 2-month Progression-Free Survival Rate
研究概览
简要总结
Hydroxychloroquine is approved for the treatment of non-cancerous illnesses such as rheumatoid arthritis and systemic lupus erythematous. Researchers in the laboratory have tested tumors from patients with pancreatic cancer and have discovered that they have certain pathways inside the cells that promote growth and survival of the tumor. Hydroxychloroquine may inactivate these pathways and results in the death of pancreatic cancer cells.
详细描述
Primary Objective
- To determine the efficacy of single-agent hydroxychloroquine in patients with metastatic pancreatic cancer previously treated with one or two prior chemotherapy regimens as measured by progression-free survival at two months
Secondary Objectives
- To assess tumor response rate, biochemical response rate (i.e. decrease in serum CA19-9 by > 30%), and overall survival
Translational/Exploratory Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically confirmed unresectable pancreatic adenocarcinoma that is metastatic to distant sites
- •Measurable disease, defined as at least one lesion that can accurately be measured in at least one dimension
- •Patients must have been treated with one or two previous lines of chemotherapy for metastatic disease with documented tumor progression or intolerance due to toxicity
- •Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
- •18 years of age or older
- •Life expectancy of greater than 12 weeks
- •ECOG performance status of 0, 1 or 2
- •Normal organ and marrow function as outlined in the protocol
- •Patients must be able to swallow pills
- •Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
排除标准
- •Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •More than two previous chemotherapy regimens for the treatment of metastatic pancreatic cancer
- •Uncontrolled brain or leptomeningeal metastases
- •History of macular degeneration, visual field changes, retinal disease, or cataracts that would interfere with funduscopic eye examinations
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to hydroxychloroquine
- •Previous treatment with chloroquine or hydroxychloroquine for other indications, such as rheumatoid arthritis, SLE or malaria prophylaxis
- •Prior treatment with any investigational drug within the preceding 4 weeks
- •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter absorption of hydroxychloroquine. Patients who have undergone a Whipple procedure for localized pancreatic cancer are not excluded from enrollment
- •History of non-compliance to medical regimens
- •Known diagnosis of glucose-6-phosphate deficiency, porphyria or psoriasis
- •Penicillamine use for Wilson's disease or any other indication
- •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
- •Pregnant or breastfeeding women
- •Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3-years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past three years: cervical cancer in situ, and basal cell or squamous cell carcinoma
- •HIV-positive individuals on combination antiretroviral therapy
研究组 & 干预措施
Hydroxychloroquine 400 mg b.i.d.
Patients received 400 mg hydroxychloroquine orally twice per day. Cycle duration was 4 weeks. Patients remained on treatment indefinitely without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
干预措施: Hydroxychloroquine (Drug)
Hydroxychloroquine 600 mg b.i.d.
Patients received 600 mg hydroxychloroquine orally twice per day. Cycle duration was 4 weeks. Patients remained on treatment indefinitely without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
干预措施: Hydroxychloroquine (Drug)
结局指标
主要结局
2-month Progression-Free Survival Rate
时间窗: Disease was evaluated radiologically at baseline and at the first restaging at 2 months.
2-month progression-free survival rate was defined as the percentage of patients absent progression (PD) or death before 2 months. Patients were considered to have experienced PD if they demonstrated either clinical deterioration resulting in withdrawal or PD per RECIST 1.0 criteria: At least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
次要结局
- Overall Survival(All patients were followed until death. Median survival follow-up in this study cohort was 60 days (95% CI: 40-184).)
- Biochemical Response Rate(Disease was evaluated radiologically at baseline and every 2 months on treatment. Median duration of treatment for this study cohort was 34 days.)
- Progression-Free Survival(Disease was evaluated radiologically at baseline and every 2 months on treatment. Median PFS follow-up in this study cohort was 46.5 days (95% CI 33-61).)
- Grade 4-5 Treatment-Related Toxicity(Adverse events were assessed each cycle throughout treatment. Participants were followed for the duration of treatment, an average of 34 days for this study population.)
- Tumor Response Rate(Disease was evaluated radiologically at baseline and every 2 months on treatment. Median duration of treatment for this study cohort was 34 days.)
研究者
Brian Wolpin, MD, MPH
Principal Investigator
Dana-Farber Cancer Institute