NCT03674814进行中（未招募）1 期
A Phase I Trial of Enzalutamide Plus the Glucocorticoid Receptor Antagonist CORT-125134 (Relacorilant) for Patients With Metastatic Castration Resistant Prostate Cancer (CRPC)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
研究概览
简要总结
The study is an open-label Phase 1 study of the combination of relacorilant with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC).
详细描述
The study is an open-label Phase 1 study of the combination of relacorilant with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC). Patients will be enrolled in 6 patient cohorts with a 6+3 design and a 28 day DLT period. Doses of relacorilant, enzalutamide will be adjusted based on safety and pharmacokinetics (PK). Once a safe dose with appropriate drug levels (PK) has been established, the cohort will be expanded to a total of 12 patients to refine safety and PK at the recommended phase II dose (RP2D).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed prostate cancer with documented metastatic disease
- •Evidence of castrate testosterone level <50ng/dl (or surgical castration)
- •Evidence of disease progression:
- •2 or more new lesions on bone scan or
- •Progressive disease on CT/MRI according to Response Evaluation Criteria in Solid Tumors 1.1 criteria or
- •Rising Prostate Specific Antigen (PSA): PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart.
- •Prior treatment with at least one line of potent androgen receptor signaling inhibitor (e.g. abiraterone, enzalutamide, apalutamide) in either castration-sensitive or castration-resistant setting.
- •Any prior therapy for castrate disease is acceptable except prior GR antagonist treatment (e.g. mifepristone or relacorilant).
- •Any other radiotherapy or radionuclide require 28-day washout prior to first dose of study drug.
- •Denosumab or zoledronic acid are allowed.
- •ECOG performance status ≤
- •Patients must have normal hepatic function as defined below:
- •Total bilirubin </=1.5 x the upper limit of normal
- •AST(SGOT)/ALT(SGPT) </=2.5 X institutional upper limit of normal
- •Albumin >/=3.0 g/dL
- •Patients must have normal bone marrow function as defined below:
- •Platelet count (plt) >/= 80,000 /microliter
- •Hemoglobin (Hgb) >/= 9 g/dL
- •Absolute neutrophil count (ANC) >/= 1500
- •Patients must have normal renal function as defined below:
- •GFR >/= 30 mL/min
- •Ability to understand and the willingness to sign a written informed consent document.
- •Patients with active Diabetes Mellitus on glucose lowering medications are eligible provided they agree to and are able to self-monitor daily blood glucose levels due to potential risk of lowering glucose levels on relacorilant.
- •Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following:
- •Condom (barrier method of contraception); AND
- •One of the following is required:
- •Established use of oral, or injected or implanted hormonal method of contraception by the female partner;
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner;
- •Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner;
- •Tubal ligation in the female partner;
- •Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months.
排除标准
- •Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid within 2 weeks prior to first dose of study drug.
- •a.Patients who have been on systemic corticosteroids with prednisone equivalent of 10mg or greater for greater than 3 months immediately prior to participation in this study must have documented ability to tolerate cessation of corticosteroids prior to enrollment.
- •Inability to swallow capsules or known gastrointestinal malabsorption.
- •Evidence of visceral disease on imaging in a patient who is an appropriate candidate for cytotoxic chemotherapy (docetaxel or cabazitaxel).
- •History of other malignancies, with the exception of: adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 malignancies who are without evidence of disease, or other cancers curatively treated with no evidence of disease for > 5 years from enrollment.
- •Blood pressure that is not controlled despite > 2 oral agents (SBP >160 and DBP >90 documented during the screening period with no subsequent blood pressure readings >160/100).
- •History of seizure disorder or active use of anticonvulsants. Medications used to treat neuropathic pain such as gabapentin or pregabalin are allowed.
- •Documented history of or current brain metastases due to seizure risk
- •Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled.
- •Active psychiatric illness/social situations that would limit compliance with protocol requirements.
- •NYHA class II, NYHA class III, or IV congestive heart failure (any symptomatic heart failure).
- •Concurrent therapy with strong inhibitors or inducers of CYP3A4 or CYP2C8 (See Section 9.12below for list of strong inhibitor or inducers) due to concerning possible drug-drug interactions
- •Presence of concurrent medical conditions requiring systemic glucocorticoids for immunosuppression (e.g. Autoimmune diseases, organ transplantation) that is active and has required glucocorticoids in the last 6 months.
研究组 & 干预措施
Dose Level
Experimental
Relacorilant will be given at a dose once daily. Enzalutamide will be given at a dose once daily.
干预措施: Enzalutamide (Drug)
Dose Level
Experimental
Relacorilant will be given at a dose once daily. Enzalutamide will be given at a dose once daily.
干预措施: Relacorilant (Drug)
结局指标
主要结局
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
时间窗: 28 days after start of dosing
Change in steady-state (C-trough) enzalutamide caused by relacorilant
时间窗: 28 days after start of dosing
次要结局
- Preliminary anti-cancer activity of relacorilant as measured by prostate specific antigen levels per response evaluation criteria in solid tumors(12 weeks after initial start of combination dosing)
- Preliminary anti-cancer activity of relacorilant as measured by tumor response per response evaluation criteria in solid tumors(12 weeks after initial start of combination dosing)
- Assess steady state relacorilant drug levels when given with enzalutamide(28 days after start of dosing)
- Assess steady state enzalutamide drug levels when given with relacorilant(28 days after start of dosing)
- Radiographic progression free survival (PFS) of the combination(Approximately 3 years)
研究者
研究点 (1)
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