NCT02966587撤回2 期
Durvalumab (MEDI4736) in Hypermutated Metastatic Castration-Resistant Prostate Cancer
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Response rate to durvalumab defined according to modified RECIST 1.1 criteria or a reduction in PSA level >= 50%
研究概览
简要总结
This phase II trial studies how well durvalumab works in treating patients with prostate cancer that is resistant to hormones and has spread to other places in the body. Monoclonal antibodies, such as durvalumab, may interfere with the ability of tumor cells to grow and spread.
详细描述
PRIMARY OBJECTIVES:
I. Determine the response rate to durvalumab in metastatic castration-resistant prostate cancer (mCRPC) patients with microsatellite instability (MSI), where response rate is defined either according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or a reduction in prostate specific antigen (PSA) level of >= 50%.
SECONDARY OBJECTIVES:
I. Determine the percent of mCRPC patients with MSI achieving a radiographic response per modified RECIST 1.1 criteria following treatment with durvalumab.
II. Determine the percent of mCRPC patients with MSI achieving a reduction in PSA level of >= 50% following treatment with durvalumab.
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
- •Patient must have evidence of castration resistant prostate cancer as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 3 [PCWG3] criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL); if a subject also received an anti-androgen, he must first progress through antiandrogen withdrawal prior to being eligible; the minimum timeframe to document failure of anti-androgen withdrawal will be four weeks
- •Patients must have received at least one of the approved products known to improve the overall survival of patients with metastatic castration resistant prostate cancer (i.e. abiraterone, enzalutamide, sipuleucel-t, radium-223, docetaxel or cabazitaxel)
- •Microsatellite instability as determined by MSI-plus assay
- •Ability to understand and the willingness to sign a written informed consent
- •Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] authorization) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Life expectancy of >= 4 months
- •Hemoglobin >= 9.0 g/dL Note: patient may receive blood transfusion to achieve a hemoglobin >= 9.1 g/dL; however, hemoglobin must be stable at or above 9 g/dL two weeks prior to dosing
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L (>= 1500 per mm^3)
- •Platelet count >= 100 x 10^9/L (>= 100,000 per mm^3)
- •Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician and the study principal investigator (PI)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =< 5 x ULN
- •Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
- •Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- •Body weight > 30 kg
排除标准
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- •Previous enrollment in the present study
- •Participation in another clinical study with an investigational product during the last 14 days
- •Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of study drug and of low potential risk for recurrence
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ)
- •Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) =< 28 days prior to the first dose of study drug (if sufficient wash-out time has not occurred due to the schedule or pharmacokinetics [PK] properties of an agent, a longer wash-out period may be required)
- •Major surgical procedure (as defined by the local/lead site PI) within 28 days prior to the first dose of investigational product (IP); Note: local surgery of isolated lesions for palliative intent is acceptable
- •Ongoing systemic therapy (other than a luteinizing hormone-releasing hormone agonists [LHRH] agonist/antagonist) for prostate cancer including, but not limited to:
- •CYP-17 inhibitors (e.g. ketoconazole, abiraterone)
- •Antiandrogens (e.g. bicalutamide, nilutamide)
- •Second generation antiandrogens (e.g. ARN-509)
- •Immunotherapy (e.g. sipuleucel-T)
- •Chemotherapy (e.g. docetaxel, cabazitaxel)
- •Radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium- 153)
- •QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 70 ms; any clinically significant abnormalities detected, require triplicate electrocardiography (ECG) results and a mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 470 ms calculated from 3 ECGs
- •Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid (steroids as pre-med for hypersensitivity reactions eg. computed tomography (CT) scan premedication is acceptable)
- •Any unresolved toxicity (> CTCAE grade 2) from previous anti-cancer therapy; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
- •Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > grade 1
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]); the following are exceptions to this criterion:
- •Patients with vitiligo or alopecia
- •Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
- •Any chronic skin condition that does not require systemic therapy
- •Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- •Patients with celiac disease controlled by diet alone
- •History of primary immunodeficiency
- •History of allogeneic organ transplant
- •History of hypersensitivity to durvalumab or any excipient
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- •Active infection including tuberculosis (TB), hepatitis B, hepatitis C, or human immunodeficiency virus. Note: TB testing will be at the discretion of the treating physician and should be in line with local practice
- •History of leptomeningeal carcinomatosis
- •Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
- •Patients of reproductive potential who are not employing an effective method of birth control; male patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period
- •Any condition that, in the opinion of the local/lead site PI, would interfere with evaluation of study treatment or interpretation of patient safety or study results
- •Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 14 days prior to study treatment start; patients with suspected brain metastases at screening should have a CT/magnetic resonance imaging (MRI) of the brain prior to study entry
- •Subjects with uncontrolled seizure
研究组 & 干预措施
Treatment (durvalumab)
Experimental
Patients receive durvalumab IV over 60 minutes on day 1. Courses repeat every 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (durvalumab)
Experimental
Patients receive durvalumab IV over 60 minutes on day 1. Courses repeat every 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity.
干预措施: Durvalumab (Biological)
结局指标
主要结局
Response rate to durvalumab defined according to modified RECIST 1.1 criteria or a reduction in PSA level >= 50%
时间窗: Up to 3 years
Will be calculated as the percentage with 95% confidence interval (CI) of the total number of subjects that achieved a response.
次要结局
- PSA PFS(From the start of treatment until PSA progression, assessed up to 3 years)
- PSA response rate as defined per the PCWG3 criteria(Up to 3 years)
- Incidence of adverse events according to NCI-CTCAE version 4.0(Up to 3 years)
- Overall survival(From the start of treatment until death from any cause, assessed up to 3 years)
- Radiographic PFS(From the start of treatment until disease progression, clinical progression, or death, whichever occurs first, assessed up to 3 years)
- Radiographic response rate defined as CR or PR using RECIST 1.1(Up to 3 years)
研究者
研究点 (2)
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