A Phase 2, Multicenter, Open-Label Study of CNTO 328 (Anti-IL-6 Monoclonal Antibody) in Combination With Mitoxantrone Versus Mitoxantrone in Subjects With Metastatic Hormone-Refractory Prostate Cancer (HRPC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 106
- 主要终点
- Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of siltuximab administered in combination with mitoxantrone and prednisone in participants with metastatic (spread of cancer cells from one part of the body to another) hormone-refractory (not responding to treatment) prostate cancer (abnormal tissue that grows and spreads in the body) (HRPC).
详细描述
This is a 2-part, open-label (all people know the identity of the intervention) multicenter (when more than 1 hospital or medical school team work on a medical research study), Phase 2 study to evaluate the safety and efficacy of the combination of siltuximab plus mitoxantrone versus mitoxantrone in participants with metastatic HRPC who have received 1 prior Docetaxel-based chemotherapy (treatment of disease, usually cancer, by chemical agents) regimen (pattern of giving treatment). Part 1 of the study is single arm where participants will receive mitoxantrone, prednisone and siltuximab. Part 2 of the study is randomized portion (the study drug is assigned by chance), consisting of 2-arms. The experimental arm will consist of treatment with mitoxantrone, prednisone and siltuximab. The control arm will consist of treatment with mitoxantrone and prednisone. Mitoxantrone will be administered at a dose of 12 milligram per square meter (mg/m^2) intravenously (into a vein) as a 30-minute infusion (a fluid or a medicine delivered into a vein by way of a needle) on Day 1 of each 3-week cycle, until disease progression or unacceptable toxicity (any harmful effect of a drug) or up to 10 cycles (a maximum total dose of approximately 120 mg/m^2). Siltuximab will be administered at a dose of 6 mg/kilogram intravenously as a 2-hour infusion, starting Day 1 of Cycle 1 to continue every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year. All participants will receive prednisone 5 mg twice daily starting with the first administration of Mitoxantrone. The duration of treatment will be a maximum of 12 months for cumulative dose. Radiologic assessments will be performed on Week 12 after the first study agent dosing, then every 9 weeks until the end of treatment and then once every 3 months until documented disease progression. Tumor (a mass in a specific area) response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. There will be short-term follow-up visits (conducted monthly for 2 months), followed by long-term follow-up visits (conducted once every 3 months). Participants' safety will also be monitored throughout the study.
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 (the study of tissue under the microscope) or cytologically (the study of cells) confirmed adenocarcinoma (a malignant epithelial tumor with a glandular organization) of the prostate
- •Radiologically (Gamma and Computed Topography [CT] scans) documented metastatic disease
- •At least 6 weeks of treatment with 1 prior docetaxel-based chemotherapy for metastatic Hormone Refractory Prostate Cancer (HRPC)
- •Disease progression, during or within 6 months of stopping of prior docetaxel-based therapy, based on one of the following: serum Prostate Specific Antigen (PSA) progression, defined as a rise in at least 2 consecutive serum PSA values, each obtained at least 1 week apart or radiologic disease progression: if disease progression is shown by bone scan only, then disease progression is defined by the appearance of 2 or more new bone lesions (abnormal area of tissue, such as a wound, sore, rash, or boil)
- •Orchiectomy (surgery to remove one or both testicles) or testosterone less than 50 nanogram per decilliter (ng/dL) by means of pharmacological/chemical castration
排除标准
- •No evidence of a brain tumor
- •No more than 1 line of chemotherapy for metastatic prostate cancer
- •No prior mitoxantrone treatment
- •Prior malignancy (other than prostate cancer) except adequately treated superficial bladder cancer, basal cell or squamous cell carcinoma (type of cancer) of the skin, or other cancer for which the subject has been disease-free for atleast 3 years
- •No Human Immunodeficiency Virus (HIV) (a life-threatening infection that you can get from an infected person's blood or from having sex with an infected person) seropositivity or hepatitis (inflammation of the liver) B or C infection
研究组 & 干预措施
Mitoxantrone+Prednisone+Siltuximab (CNTO 328) (Part 1)
In Part 1, mitoxantrone 12 milligram per square meter (mg/m^2) will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m^2) along with siltuximab 6 mg/kilogram (mg/kg) intravenously as a 2 hour-infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year; and prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.
干预措施: Mitoxantrone (Drug)
Mitoxantrone+Prednisone+Siltuximab (CNTO 328) (Part 1)
In Part 1, mitoxantrone 12 milligram per square meter (mg/m^2) will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m^2) along with siltuximab 6 mg/kilogram (mg/kg) intravenously as a 2 hour-infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year; and prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.
干预措施: Siltuximab (Drug)
Mitoxantrone+Prednisone+Siltuximab (CNTO 328) (Part 1)
In Part 1, mitoxantrone 12 milligram per square meter (mg/m^2) will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m^2) along with siltuximab 6 mg/kilogram (mg/kg) intravenously as a 2 hour-infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year; and prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.
干预措施: Prednisone (Drug)
Mitoxantrone+Prednisone+Siltuximab (Part 2)
In Part 2, mitoxantrone 12 mg/m^2 will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m^2) along with siltuximab 6 mg/kg intravenously as a 2-hour infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year; and prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.
干预措施: Mitoxantrone (Drug)
Mitoxantrone+Prednisone+Siltuximab (Part 2)
In Part 2, mitoxantrone 12 mg/m^2 will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m^2) along with siltuximab 6 mg/kg intravenously as a 2-hour infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year; and prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.
干预措施: Siltuximab (Drug)
Mitoxantrone+Prednisone+Siltuximab (Part 2)
In Part 2, mitoxantrone 12 mg/m^2 will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m^2) along with siltuximab 6 mg/kg intravenously as a 2-hour infusion every 2 weeks until disease progression or unacceptable toxicity or up to a maximum of 1 year; and prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.
干预措施: Prednisone (Drug)
Mitoxantrone+Prednisone (Part 2)
In Part 2, mitoxantrone 12 mg/m^2 will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m^2) along with prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.
干预措施: Mitoxantrone (Drug)
Mitoxantrone+Prednisone (Part 2)
In Part 2, mitoxantrone 12 mg/m^2 will be given intravenously as a 30-minute infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity or up to 10 cycles (a maximum cumulative dose of approximately 120 mg/m^2) along with prednisone 5 mg orally twice daily starting with the first administration of mitoxantrone.
干预措施: Prednisone (Drug)
结局指标
主要结局
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to 12 weeks after last dose administration
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Part 2: Progression Free Survival (PFS)
时间窗: Randomization, Week 12, then every 9 weeks until 1 month after last dose administration, then every 3 months until disease progression or death, up to 2 years
The PFS is the time from the date of randomization until the first documented sign of progression (at least a 20 percent increase in the sum of the longest diameter \[LD\] of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new target or non-target lesions as per Response Evaluation Criteria in Solid Tumors \[RECIST\] or 3 or more new skeletal lesions on bone scan with confirmation of second bone scan or with clinical deterioration) or death, whichever occurs first.
次要结局
- Time to Clinical Deterioration (TtCD)(Start of treatment (Part 1)/Randomization (Part 2), Week 1 of each cycle up to 1 month after last dose administration, and thereafter every 3 months until clinical deterioration or death, up to 2 years)
- Number of Participants With Palliative Response(Start of treatment (Part 1)/Randomization (Part 2), Week 1 of each cycle up to 1 month after last dose administration, and thereafter every 3 months up to 2 years)
- Overall Survival (OS)(Start of treatment (Part 1)/Randomization (Part 2) until death, up to 2 years)
- Number of Participants With Prostate Specific Antigen (PSA) Response(Start of treatment (Part 1)/Randomization (Part 2), Week 1 of each cycle up to 1 month after last dose administration, and thereafter every 3 months until disease progression, up to 2 years)