Phase 2 Trial Combining EPI-7386 With Enzalutamide and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- PSA progesterone-free survival (PFS)
研究概览
简要总结
The purpose of this study is to study the effects of EPI-7386 in combination with Enzalutamide on participants diagnosed with prostate cancer. The main goals of this study are to evaluate the antitumor activity of EPI-7386 in combination with enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC), and to evaluate the pharmacokinetics (PK) of EPI-7386 when dosed in combination with enzalutamide. Participants will will take the study drug, EPI-7360, twice a day by mouth and enzalutamide once a day by mouth, alongside clinic visits every two weeks.
详细描述
EPI-7386 is an investigational drug that works by blocking the androgen receptor at a different site compared to the approved androgen receptor blockers. This may increase the effectiveness of this drug and increase the effectiveness of approved androgen receptor blockers when taken together. EPI-7386 is a new drug; therefore, its effectiveness and safety in prostate cancer patients must be studied before it is approved by the Food and Drug Administration. EPI-7386 is experimental because it is not currently approved by the Food and Drug Administration (FDA). Enzalutamide is approved by the FDA for patients whose prostate cancers has spread after receiving treatment. The hypothesis is that adding EPI-7386 to standard hormone therapy will be more effective in treating cancer compared to usual treatment, with the long term goal of discovering more about hormone therapy as a treatment for cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Subjects must have histologically or cytologically confirmed prostate adenocarcinoma without small cell or neuroendocrine features (please note: >10% small cell or neuroendocrine differentiation will be excluded).
- •Subjects must have received no prior second-generation antiandrogen therapies for this disease. Androgen deprivation with LHRH agonist/antagonist therapy or history of bilateral orchiectomy that started less than 12 weeks before study enrollment is allowed.
- •Subjects may have either de novo or recurrent metastatic disease. Presence of metastatic disease at study entry documented by 1 or more lesions - bone, lymph node, soft tissue, or visceral metastases - observed by any imaging technique.
- •Age >18 years. This study will be limited to adults only.
- •Evidence of metastatic disease by conventional CT and bone scans, MRI or positron emission tomography (PET) scans.
- •ECOG performance status of 0 to
- •Subjects must have normal organ and marrow function as defined below:
- •Absolute neutrophil count >1000/μL; platelet count >100 000/μL; hemoglobin >8.5 g/dL) at screening. Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 28 days prior to the hematologic laboratory values obtained at screening).
- •Total bilirubin (TBIL) <2 × the upper limit of normal (ULN) at screening, except subjects with documented Gilbert syndrome who must have a TBIL <3 mg/dL
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <5 × ULN at screening
- •Creatinine clearance ≥45 mL/min and/or estimated glomerular filtration rate (eGFR) ≥30
- •Albumin >30 g/L (3.0 g/dL) at screening
- •Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days before the start of study treatment.
- •Radiation therapy is allowed at any time, as deemed appropriate by the treating investigator.
- •Subjects of child-producing potential agree to use highly effective contraceptive methods (i.e., barrier contraception measures such as a male condom with spermicide during intercourse) and avoid sperm donation during the study treatment and for 3 months after the last dose of study treatment. A man is considered to be of child-producing potential, unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. Partners of participants must also practice approved forms of birth control.
- •Subjects must have the ability to understand and the willingness to sign a written informed consent form (ICF).
- •Members of all races and ethnic groups are eligible for this trial. At least ≥ 20% of enrolled subjects must be of African American descent. (self-reported).
排除标准
- •Evidence of mCRPC.
- •Receipt of any other investigational agents.
- •Diagnosis of another clinically significant malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or noninvasive malignancies, as determined by the PI or CoPI.
- •Gastrointestinal issues affecting absorption (e.g., gastrectomy).
- •Known history of seizure or conditions that may predispose the subject to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, or brain arteriovenous malformation. Subjects with brain metastases/central nervous system (CNS) disease that are treated prior to enrollment will be allowed in this clinical trial.
- •Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
- •Use of compounds known to be strong inducers of CYP3A within 30 days prior to start of study drug treatment, and strong inhibitors of CYP2C8 within 14 days of the first dose of study treatment.
- •Use of narrow therapeutic index sensitive CYP2C8 substrates (e.g., daprobustat, dasabuvir, repaglinide, paclitaxel) or sensitive substrates for CYP3A.
- •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 considered by the Investigator to limit compliance with study requirements.
研究组 & 干预措施
EPI-7386 + Enzalutamide
EPI-7386 at 600 mg twice daily orally with standard of care Enzalutamide at 160 mg, once daily, orally for 36 months of treatment (11 cycles).
干预措施: EPI-7386 (Drug)
EPI-7386 + Enzalutamide
EPI-7386 at 600 mg twice daily orally with standard of care Enzalutamide at 160 mg, once daily, orally for 36 months of treatment (11 cycles).
干预措施: Enzalutamide (Drug)
EPI-7386 + Enzalutamide
EPI-7386 at 600 mg twice daily orally with standard of care Enzalutamide at 160 mg, once daily, orally for 36 months of treatment (11 cycles).
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
结局指标
主要结局
PSA progesterone-free survival (PFS)
时间窗: Post-intervention at Week 4
Progression free survival (PFS) is measured from the date of the start of the treatment to the date of progression or death and is censored at the date of last followed for those that have not progressed
Radiographic PFS (rPFS)
时间窗: Post-intervention at Week 4
Progression free survival (PFS) is measured from the date of the start of the treatment to the date of progression or death and is censored at the date of last followed for those that have not progressed
ORR (confirmed)
时间窗: Post-intervention at Week 4
Objective response rate (ORR)
Biochemical response rate
时间窗: Post-intervention at Week 4
Defined as prostate-specific antigen (PSA) undetectable (\<0.2 ng/mL) at 6 months after treatment. The true BRR for the study population will be estimated based on the number of biochemical responses using a binomial distribution, and its confidence interval (CI) will be estimated using Wilson's method.
次要结局
- AUC0-24(Beginning of treatment day 1, at week 2, week 4, week 6)
- Maximum concentration (Cmax)(Beginning of treatment day 1, at week 2, week 4, week 6)
- Predose Plasma Concentration(Beginning of treatment day 1, at week 2, week 4, week 6)
- Time to reach Cmax (Tmax)(Beginning of treatment day 1, at week 2, week 4, week 6)
- Terminal elimination half-life(Beginning of treatment day 1, at week 2, week 4, week 6)
- Volume of distribution at steady state after extravascular administration(Beginning of treatment day 1, at week 2, week 4, week 6)
- Clearance after extravascular administration(Beginning of treatment day 1, at week 2, week 4, week 6)
- Treatment-emergent adverse events(Post-intervention at Week 4)
- Rate of abnormalities in clinical laboratory parameters(Baseline, 2 weeks, 11 weeks, and 20 weeks after beginning treatment)
- Rate of abnormalities in vital sign measurements(Post-intervention at Week 4)
- Rate of abnormalities in electrocardiograms (ECGs)(At screening and beginning of treatment on day 1 of cycle 1 (each cycle is 14 days))
- Changes in Eastern Cooperative Oncology Group (ECOG) performance status(Post-intervention at Week 4)
研究者
Pedro Barata, MD, MSc
Director, Clinical Genitourinary Medical Oncology Research Program, Prinicipal Investigator
Case Comprehensive Cancer Center