Phase II Trial of In-Situ Autologous Vaccination With Intratumoral and Systemic Hiltonol® (Poly-ICLC) Administered to Prostate Cancer Patients on Active Surveillance
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Proportion of subjects without Gleason group upgrade after treatment
研究概览
简要总结
This is a partially blinded randomized controlled phase II pilot study comparing Poly-ICLC (Hiltonol®) treatment vs no treatment, for prostate cancer participants on active surveillance.
详细描述
114 prostate cancer participants on active surveillance will be randomized 2:1 into treatment group, A or control group B respectively. Enrolled group A study participants will receive standard of care (SOC) plus intratumoral (IT) and intramuscular (IM) injections of study drug Poly-ICLC (Hiltonol®) as follows:
Preconditioning: week 1: Paired IM Poly-ICLC, 1.5 mg to reduce tumor induced suppression
Immune Priming: week 2, intratumor poly-ICLC 1.0 mg once,
Boosting: Wk. 3 - 10: Paired 1.5 mg IM poly-ICLC weekly
Maintenance: Month 3-12, Paired IM Poly-ICLC once a month
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
- Double (Participant, Outcomes Assessor)
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
- •Written informed consent and HIPAA authorization for release of personal health information.
- •NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age > 18 years at the time of consent.
- •ECOG Performance Status of 0-1 within 14 days prior to being registered for protocol therapy (Study Procedure Manual).
- •Histologically confirmed adenocarcinoma of the prostate (with previous diagnostic tissue available for tumor marker analysis).
- •• ISUP Grade 1(Gleason 3+3) and Grade 2 (Gleason 3+4) and Grade 1 (Gleason 3+3, with PSA≥10, or stage ≥ T2b)
- •Estimated life expectancy is ≥ 10 years
- •Candidate for primary curative therapy (Radical prostatectomy or radiation) if cancer progresses.
- •Tolerated previous transrectal ultrasound guided biopsy procedure under local anesthetic
- •Uncomplicated previous TRUS biopsy procedure (i.e., no prior hospitalization due to sepsis, prostatic abscess or severe hemorrhage following TRUS prostate biopsy)
- •Willing to undergo the intratumoral (IT) injection of the Poly-ICLC into the prostatic tumor as per the protocol
- •No prior hormonal therapy with exception of with the exception of oral 5-alpha-reductase inhibitors (finasteride, dutasteride, etc.). Subjects should be off the medication ≥ 6 months from screening
- •No prior radiation therapy (external beam or brachytherapy) to the pelvis or prostate.
- •No clinically significant infections as judged by the treating investigator.
- •No characteristics suggesting a potential higher risk of infection with intraprostatic injections:
- •Recurrent urinary tract infections or history of prostatitis within 3 months prior to enrollment into the study.
- •Urine analysis positive for nitrites and leucocyte esterase. Such subjects could be considered for the study after treatment and resolution of the infection.
- •Active proctitis
- •History of prostatic abscess
- •Taking immunosuppressive medication including systemic corticosteroids
- •Active hematologic malignancy
- •No uncontrolled angina, congestive heart failure or MI within 6 months.
- •Subjects with history of HIV (if CD4+ T cell counts are ≥350 cells/μL on established ART therapy), Hepatitis B (with viral load below limits of quantification) or Hepatitis C (who have completed a curative therapy and have a viral load below the limit of quantification) are eligible for this study.
- •No treatment with any investigational agent for any medical condition within 28 days prior to being registered for protocol therapy.
- •Patients with the potential for impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Contraception must be continued for at least 2 months following the last dose of poly-ICLC. While animal reproductive studies have been negative, the simulated viral infection and anti-proliferative activity of this experimental drug may theoretically affect the developing fetus or nursing infant.
- •Adequate end organ function as determined by the following laboratory values:
- •White blood cell count (WBC) ≥ 2.5 k/mm^3
- •Absolute neutrophil count (ANC) ≥ 1.5 k/mm^3
- •Hemoglobin (Hgb) ≥ 8.0 g/dL
- •Platelets ≥ 100 k/mm^3
- •Calculated creatinine clearance of > 60 cc/min using the Cockcroft-Gault formula:
- •Males: [(140 - Age in years) × Actual Body Weight in kg]/[72 × Serum Creatinine (mg/dL)]
- •Bilirubin ≤ 2.0 x ULN
- •Aspartate aminotransferase (AST) ≤ 2.5 x ULN
- •Alanine aminotransferase (ALT) ≤ 2.5 x ULN
排除标准
- •Received local or systemic curative therapy for prostate cancer
- •Subjects with neuroendocrine tumors
- •ISUP Gleason Grade Group (>3), or Gleason 3+3 plus PSA ≤ 10 or Stage ≤T2a
- •Evidence of locally advanced disease
- •Subject has evidence of any other malignancy
- •Allergy to any antibiotics, as IT administration requires prophylactic antibiotics.
研究组 & 干预措施
Hiltonol (Poly-ICLC)
Enrolled study subjects will receive paired intramuscular (IM) and intertumoral. (IT) injections of the drug Poly-ICLC (Hiltonol®) as follows: Paired 1.5 mg IM (week 1), 1 mg IT once (week 2), followed by paired 1.5 mg IM weekly from weeks 3-through10, and at weeks 14, 18, 22, 26, 30, 34, 38, 42 and 46 with a 4-week rest period between IM injections.
干预措施: Poly-ICLC intramuscular (IM) injection (Drug)
Hiltonol (Poly-ICLC)
Enrolled study subjects will receive paired intramuscular (IM) and intertumoral. (IT) injections of the drug Poly-ICLC (Hiltonol®) as follows: Paired 1.5 mg IM (week 1), 1 mg IT once (week 2), followed by paired 1.5 mg IM weekly from weeks 3-through10, and at weeks 14, 18, 22, 26, 30, 34, 38, 42 and 46 with a 4-week rest period between IM injections.
干预措施: Poly-ICLC, Intertumoral (IT) injection (Drug)
结局指标
主要结局
Proportion of subjects without Gleason group upgrade after treatment
时间窗: at 36 months
Proportion of subjects without Gleason group upgrade after treatment with Poly-ICLC or control, as determined by histological examination of prostate biopsy at the three years time point.
Proportion of subjects without Gleason group downgrade after treatment
时间窗: at 36 months
Proportion of subjects with Gleason group downgrade after treatment with Poly-ICLC or control, as determined by histological examination of prostate biopsy at the 3 years time point.
次要结局
- Number of subjects who experience adverse events per NCI-CTCAE 5.0(At 36 months)
- Number of subjects who receive prostate cancer treatment(At 36 months)
研究者
Ashutosh Kumar Tewari
Professor and System Chair, Milton and Carroll Petrie Department of Urology
Icahn School of Medicine at Mount Sinai