NCT02199197已完成2 期
A Phase 2 Randomized Study Comparing Radium Ra 223 Dichloride Plus Enzalutamide With Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Fold Change in Serum N-telopeptides From Baseline
研究概览
简要总结
Study of Radium Ra 223 dichloride with enzalutamide compared to enzalutamide alone in men with metastatic castration refractory prostate cancer
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
- 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 documented adenocarcinoma of the prostate.
- •Men at least 18 years of age and life expectancy of greater than or equal to 6 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
- •Metastatic disease as evidenced by both lymphadenopathy and bony metastases or just bony metastases on baseline bone scan and/or computed tomography (CT) scan or MRI of the abdomen and pelvis within 28 days of registration. Chest imaging is only required if clinically indicated or if there is known disease in the chest.
- •Castration resistant prostatic adenocarcinoma. Subjects must have castrate levels of serum testosterone (less than 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy.
- •Previously received docetaxel or are not healthy enough per clinical judgment or declined to receive it
- •Evidence of disease progression on or after the most recent systemic treatment defined by the following criteria:
- •Prostate-Specific Antigen (PSA): Increasing serum PSA levels as defined by the Prostate Cancer Working Group 2 (PCWG2), determined by 2 consecutive measurements (compared to a baseline or nadir value). If the third measurement is below the second, then a fourth measurement must be greater than the second. The confirming third or fourth measurement must be greater or equal to 2 ng/mL. PSA progression must have occurred within 15 months of registration (with at least 7 days between each PSA measurement). Additionally, the PSA progression as described above should have occurred during or after the most recent systemic treatment for prostate cancer.
- •Measurable disease: greater than or equal to 20% increase in the sum of the short axis diameter of all measurable lymph nodes or the development of any new measurable lymphadenopathy by RECIST 1.1 and PCWG2 criteria.
- •Non-measurable disease:
- •Lymph node disease: The appearance of 1 or more new lymphadenopathy, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response.
- •Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression.
- •Symptomatic bone metastases
- •Adequate hematologic, renal, and liver function as evidenced by laboratory test results. (Transfusion of blood products are not allowed to normalize blood parameters within 4 weeks of the first radium treatment.)
- •Subjects who have previously received docetaxel or are ineligible for docetaxel and who are candidates for treatment with enzalutamide alone or enzalutamide in combination with Radium-223
- •Men must agree to use adequate contraception beginning at the signing of the Informed Consent Form until at least 6 months after the last dose of study drug. Because of the potential side effect on spermatogenesis associated with radiation, men who are sexually active must agree to use condoms and their female partners of reproductive potential must agree to use a highly effective contraceptive method during and for 6 months after completing treatment.
- •Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines to ensure compliance with HIPAA regulations.
排除标准
- •The presence of known brain metastases, malignant pleural effusions, or malignant ascites. Brain MRI is required at screening only if clinically indicated.
- •Visceral metastases as assessed by chest, abdominal or pelvic computed tomography (CT) (or other imaging modality)
- •Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases
- •Prior treatment with enzalutamide.
- •Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than the protocol based treatment. LHRH agonist or antagonist therapy, and supportive non-cancer directed therapies like bisphosphonates or denosumab are allowed.
- •Prior cytoxic chemotherapy with the exception of docetaxel or cabazitaxel. Treatment with docetaxel or cabazitaxel must be discontinued greater than 4 weeks from the time of enrollment, and recovery of adverse events (AEs) to grade 1 or baseline (however, ongoing neuropathy is permitted).
- •Major surgery within 30 days prior to start of study drug
- •Current, untreated pathologic long-bone fractures, imminent pathologic long-bone fractures (cortical erosion on radiography greater than 50%).
- •Prior hemi-body external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count (ANC), and platelets.
- •Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) within 4 weeks prior to screening
- •Lymphadenopathy exceeding 3 cm in short-axis diameter
- •Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis.
- •Current or imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.
- •Any other serious illness or medical condition in the opinion of the investigator, such as but not limited to:
- •Any greater than or equal to Grade 2 infection as defined by NCI-CTCAE version 4.
- •Cardiac failure New York Heart Association (NYHA) III or IV
- •Crohn's disease or ulcerative colitis
- •Bone marrow dysplasia
- •Fecal incontinence
- •Concomitant use of narrow therapeutic index drugs that are metabolized by CYP3A4 (i.e. alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), CYP2C9 (phenytoin, warfarin), and CYP2C19 (S-mephenytoin). [Note: Patients on stable doses of anti-coagulation with warfarin and fentanyl will be eligible, as long as they are monitored closely with additional international normalized ratio (INR) monitoring].
- •Any infection requiring parenteral antibiotic therapy or causing fever (temperature greater than 100.5 degrees F or 38.1 degrees C) within 1 week prior to registration.
- •Concurrent other malignancy with the exception of: a) cutaneous squamous cell and basal carcinomas, b) adequately treated stage 1-2 malignancy , c) adequately treated stage 3-4 malignancy that had been in remission for greater than or equal to 2 years at the time of registration.
- •Inability to comply with the protocol and/or not willing or not available for follow-up assessments
- •Any medical intervention or other condition which, in the opinion of the Principal Investigator could compromise adherence with study requirements or otherwise compromise the study's objectives
研究组 & 干预措施
Radium Ra 223 Dichloride and Enzalutamide
Experimental
Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.
干预措施: Radium Ra 223 Dichloride (Drug)
Radium Ra 223 Dichloride and Enzalutamide
Experimental
Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles.
干预措施: Enzalutamide (Drug)
Enzalutamide alone
Active Comparator
Enzalutamide administered as a single agent for 6 28-day cycles.
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Fold Change in Serum N-telopeptides From Baseline
时间窗: From prior to start of treatment to end of treatment or disease progression (approximately 6 months)
Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.
Number of Participants With Adverse Events
时间窗: From first dose of study treatment to 30 days following last dose (approximately 7 months)
Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.
次要结局
- Prostate Specific Antigen (PSA) Progression Free Survival (PFS)(Up to 2 years (24 months))
- Radiographic Progression Free Survival (PFS)(Up to 2 years (24 months))
- Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)(Up to 2 years (24 months))
- Count of Prostate Specific Antigen (PSA) Responses(Up to 2 years after start of study treatment)
- Count of Radiographic Responses(Up to 2 years after start of study treatment)
- Overall Survival (OS)(Up to 40 months)
研究者
研究点 (1)
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