NCT02146833终止2 期
A Phase-2, Open-Label Study of Oral Selinexor (KPT-330) in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Overall Clinical Benefit Response (CBR)
研究概览
简要总结
This is an open-label, Phase 2 clinical study of the oral Selective Inhibitor of Nuclear Export (SINE) selinexor (KPT-330) in patients with metastatic castration-resistant prostate cancer (mCRPC).
详细描述
This is a Phase 2, open-label study to explore the effect of selinexor (KPT-330) therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Approximately 50 patients are planned for enrollment. Patients will receive an oral dose of selinexor on one of three dosing schedules.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.
- •Must have received at least one agent known to impact survival (abiraterone, enzalutamide, etc.).
- •Eastern Cooperative Oncology Group (ECOG) less than or equal to (≤ 2) or a Karnofsky Performance Status (KPS) ≥ 60%.
- •Serum testosterone levels less than (<) 50 ng/ml.
- •Ongoing gonadal androgen deprivation therapy with luteinising hormone-releasing hormone (LHRH) analogues or orchiectomy. Participants, who have not had an orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at appropriate frequency for the duration of the study.
- •Progression of disease despite androgen ablation shown by objective, documented evidence of disease progression (excluding prostate-specific antigen [PSA]), defined as one or both of the following:
- •Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Bone disease progression defined by modified Prostate Cancer Clinical Trials Working Group 2 (PCWG2) with two or more new lesions or bone scan
- •Discontinuation of all glucocorticoids prescribed to specifically treat prostate cancer (e.g., as a secondary hormonal manipulation) greater than (>) 4 weeks prior to receiving first dose of study drug. Glucocorticoids prescribed for a chronic non-cancer-related illness (e.g., asthma or chronic obstructive pulmonary disease [COPD]) that is well controlled with medical management are permissible to an equivalent of ≤ 10 milligrams (mg) prednisone daily.
- •Laboratory requirements:
- •White blood cell (WBC) count > 3,000/microliter (μL)
- •Absolute neutrophil count (ANC) > 1,500/μL
- •Hemoglobin ≥8.0 gram per deciliter (g/dL)
- •Platelet count ≥150,000/μL
- •Serum albumin ≥3.0 g/dL
- •Calculated or measured creatinine clearance > 30 milliliter per minute (mL/min)
- •A biopsy documenting prostate cancer in a target lesion (e.g., lymph node, bone lesion, or soft tissue lesion) within 3 months prior to study entry.
- •No evidence of chronic or acute disseminated intravascular coagulation or bleeding tendency.
- •Participant must be willing and able to comply with protocol requirements. All participants must sign an informed consent indicating that they are aware of the investigational nature of this study.
- •Participant must be willing and able to sign an authorization for the release of their protected health information for study purposes.
排除标准
- •Histologic variants other than adenocarcinoma in the primary tumor.
- •Participants who require or may be expected to require urgent treatment with docetaxel during the study (e.g., participants with visceral metastases).
- •Abnormal hepatic function:
- •Bilirubin > 2 times the upper limit of normal (2 x ULN) (except participants with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must not have a total bilirubin of > 3 x ULN)
- •Aspartate transaminase (AST) and alanine transaminase (ALT) > 2.5 x ULN (except participants with known liver involvement of their mCRPC who must not have an AST and ALT > 5 x ULN)
- •Therapy with other hormonal therapy, including any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES) within 4 weeks prior to receiving first dose of study drug.
- •Therapy with samarium-153, strontium-89, or radium-223 within 8 weeks prior to first dose of study drug.
- •Uncontrolled infection or concomitant illness that is not controlled with medical management.
- •Prior external beam radiation therapy completed < 3 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug.
- •Any "currently active" second malignancy, other than non-melanoma skin cancer. Participants are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next 3 months.
- •Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.
- •Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study.
- •Severely compromised immunological state, including known human immunodeficiency virus (HIV).
- •Known acute or chronic hepatitis B or C.
- •Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 3-week washout period before treatment initiation.
- •Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study treatment. Participants receiving ongoing bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to receiving first dose of study treatment. Participants on stable doses of bisphosphonates who show subsequent tumor progression may continue on this medication.
- •Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- •History or presence of serious uncontrolled ventricular arrhythmias or presence of uncontrolled atrial fibrillation.
- •Clinically significant resting bradycardia (< 50 beats per minute).
- •Any of the following within 3 months prior to study entry: myocardial infarction severe/unstable angina, Coronary Artery Bypass Graft, Grade 3 or 4 Congestive Heart Failure, Cerebrovascular Accident, Transient Ischemic Attack, or Pulmonary Embolism.
- •Uncontrolled hypertension, as defined by a systolic blood pressure > 160 mm Hg and/or a diastolic blood pressure > 90 mm Hg with or without anti-hypertensive medication.
- •Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring 2 or more interventions per month.
- •Angina at rest.
- •Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE), version 4.03 Grade of ≤
- •Chemotherapy induced alopecia or Grade 2 neuropathy is allowed.
- •Any condition or situation, which in the Investigator's opinion, may put the participant at significant risk, confound the study results, or interfere significantly with the participant's participation in the study.
- •Men with a female partner of child-bearing potential, (defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months), who as a couple are unable or unwilling to employ two forms of highly effective contraception (e.g., male condom with spermicide, diaphragm with spermicide, intra-uterine device). Two methods of contraception must be used by participants and their partners through the study and for 3 months after the end of study treatment.
- •Body mass index (BMI) < 1.2 m^2, in order to prevent a participant from receiving a dose of selinexor > 70 mg/m^2.
研究组 & 干预措施
Selinexor Dosing Regimen 1
Experimental
80 mg twice weekly for 4 weeks (8 doses per 28-day cycle)
干预措施: Selinexor (Drug)
Selinexor Dosing Regimen 2
Experimental
80 mg once weekly for 4 weeks (4 doses per 28-day cycle)
干预措施: Selinexor (Drug)
Selinexor Dosing Regimen 3
Experimental
60 mg twice weekly for 2 weeks, then 1 week off (4 doses per 21-day cycle)
干预措施: Selinexor (Drug)
结局指标
主要结局
Percentage of Participants With Overall Clinical Benefit Response (CBR)
时间窗: At 12 weeks
CBR was defined as the point estimate of the percentage of participants who had complete response (CR), partial response (PR), or stable disease (SD) at 12 weeks as per the Response Evaluation Criteria in Solid Tumors (RECIST v.1.1; soft tissue lesions). CR: Disappearance of all target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taken as reference the baseline sum diameter. SD: steady state of disease; non-CR or non-PR or non-progressive disease.
次要结局
- Percentage of Participants With Best Overall Response: RECIST v1.1 Criteria(From the date of first documented occurrence of response (CR or PR) until the date of documented progression or last disease assessment (up to 23 months))
- Pain Intensity Index (PPII) Total Score(Baseline up to 30 days after last dose of study treatment (up to 23 months))
- Progression Free Survival (PFS)(From first dose of study treatment to time of disease progression or death, censored date (up to 23 months))
- Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Events (TESAE)(From screening up to 23 months)
- Absolute Values of Prostate Specific Antigen (PSA) Levels(Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 (each cycle of 28 days) and End of Treatment (30 days after last dose of study treatment))
- Percent Change From Baseline in Prostate Specific Antigen Levels(Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 (each cycle of 28 days) and End of Treatment (30 days after last dose of study treatment))
- Prostate Specific Antigen Response Rate(Baseline up to 12 weeks)
- Overall Survival (OS)(From first dose of study treatment to death, censored date (up to 23 months))
研究者
研究点 (1)
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