Phase Ib Trial of Encapsulated Rapamycin (eRapa) in Prostate Cancer Patients Under Active Surveillance
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
研究概览
简要总结
This study is to determine the safety, pharmacokinetics/pharmacodynamics, and immunologic impact of encapsulated rapamycin in patients with low risk prostate cancer under active surveillance. There will be four groups of patients, each receiving a different dose of rapamycin.
详细描述
This is a phase Ib trial of encapsulated rapamycin to determine safety, pharmacokinetics/pharmacodynamics, and immunologic impact in patients with low risk prostate cancer under active surveillance. This new formulation, encapsulated rapamycin (sirolimus), provides a more predictable bioavailability of this drug than [the other formulation]. The encapsulated and targeted rapamycin (eRapa) can be delivered at a consistent and lower dosage, not only improving the toxicity profile but also capitalizing on the newly appreciated mechanism of partial and/or intermittent mTOR inhibition, making eRapa an ideal immuno-oncologic and chemopreventative agent. Low dose rapamycin has been shown to prevent cancer formation, progression, and/or recurrence in the majority of cancer histologies including the most prevalent: lung, breast, prostate, and colon cancers.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •The patient must:
- •Have pathologically (histologically) proven diagnosis of prostate cancer with a Gleason score ≤7 (3+4) and already undergoing active surveillance
- •Be able to give informed consent
- •Be age 18 or older
排除标准
- •Prostate cancer with a Gleason score >7
- •Unable to give informed consent
- •Age < 18
- •Immunosuppressed state (e.g., HIV, use of chronic steroids)
- •Active, uncontrolled infections
- •On medications with strong inhibitors or inducers of CYP3A4 and or P-gp.
- •On agents known to alter rapamycin metabolism significantly (Appendix H)
- •Have another cancer requiring active treatment (except basal cell carcinoma or squamous cell carcinoma of the skin)
- •Individuals with a reported history of liver disease (e.g., cirrhosis)
- •Individuals who are not a good candidate for active surveillance in their treating physician's opinion
- •Have a medical condition (e.g., anemia, anticoagulated) for which repeated phlebotomy may be problematic.
- •Uncontrolled hypertension.
- •Individuals that have abnormal screening vital organ function prior to enrollment
- •Liver Function Test
- •Bilirubin >2.0
- •Alkaline phosphatase >5x upper limit of normal (ULN)
- •ALT/AST >2x ULN
- •Complete Blood Count:
- •WBC elevated above the normal standard per the testing laboratory
- •Hgb/Hct below the normal standards of the testing lab
- •Platelets below the normal standards of the testing lab
- •Total Cholesterol >240 mg/dL
- •Triglycerides > 200 mg/dL
- •Serum creatinine >2 and BUN >30
- •Urinary protein: proteinuria >1+ on urinalysis or >1 gm/24hr
研究组 & 干预措施
Cohort 1: 0.5 mg weekly
Oral administration with consecutive enrollment of overlapping dose-escalation cohorts, total treatment period 3 months. Patients will conclude treatment with previously scheduled standard of care prostate biopsy.
eRapa (encapsulated rapamycin) is dosed at 0.5 mg every week.
干预措施: eRapa (encapsulated rapamycin) (Drug)
Cohort 2: 1 mg weekly
Oral administration with consecutive enrollment of overlapping dose-escalation cohorts, total treatment period 3 months. Patients will conclude treatment with previously scheduled standard of care prostate biopsy.
eRapa (encapsulated rapamycin) is dosed at 1 mg every week.
干预措施: eRapa (encapsulated rapamycin) (Drug)
Cohort 3: 0.5 mg daily
Oral administration with consecutive enrollment of overlapping dose-escalation cohorts, total treatment period 3 months. Patients will conclude treatment with previously scheduled standard of care prostate biopsy.
eRapa (encapsulated rapamycin) is dosed at 0.5 mg daily.
干预措施: eRapa (encapsulated rapamycin) (Drug)
Cohort 4: 1 mg daily
Oral administration with consecutive enrollment of overlapping dose-escalation cohorts, total treatment period 3 months. Patients will conclude treatment with previously scheduled standard of care prostate biopsy.
eRapa (encapsulated rapamycin) is dosed at 1 mg daily.
干预措施: eRapa (encapsulated rapamycin) (Drug)
结局指标
主要结局
Primary Safety and Tolerability (Incidence of Treatment-Emergent Adverse Events)
时间窗: This will be completed after all dosing cohorts have been enrolled and treated, anticipated to occur after 1 year.
To compare safety between dosing cohorts of eRapa by evaluating the number, frequency, duration, and relation of toxicity events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 at the 12 week time point.
次要结局
- Secondary Pharmacokinetics: Exposure Trough Levels(Cohorts 3 and 4 PK analysis will occur during the first week of treatment.)
- Secondary Pharmacodynamics: mTOR inhibition in PBMC by assessment of phosphorylation of S6(Cohorts 1 and 2 PD analysis will occur during the first week. Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.)
- Secondary Pharmacokinetics: AUC(Cohorts 1 and 2 PK analysis will occur during the first week. Cohorts 3 and 4 PK analysis will occur during week 12 of treatment.)
- Secondary Immunologic Response: T cell phenotype overall study-wide(Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).)
- Secondary Immunologic Response: T cell function overall study-wide(Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).)
- Secondary Pharmacodynamics: mTOR inhibition during final week of treatment(Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.)
- Secondary Immunologic Response: T cell function individually(Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).)
- Secondary Pharmacodynamics: mTOR inhibition upon initial dose(Cohorts 1 and 2 PD analysis will occur during the first week.)
- Secondary Pharmacodynamics: mTOR inhibition first week of daily dosing(Cohorts 3 and 4 PD analysis will occur during week 12 of treatment.)
- Secondary Immunologic Response: T cell phenotype within each dosing cohort(Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).)
- Secondary Immunologic Response: T cell function within each dosing cohort(Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).)
- Secondary Quality of Life Analysis(Assessments performed baseline, after completion of therapy (approximately 12 weeks), and after 6 months.)
- Secondary Immunologic Response: T cell phenotype individually(Assessments will occur at baseline, during (after 4 weeks), after short-term completion of treatment (after 12 weeks), and long-term completion of treatment (6 months).)