A Phase I/II, Open-label, Dose-escalation Study of MDX-010 Administered Every 3 Weeks for 4 Doses in Patients With Metastatic Hormone-Refractory Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 13
- 主要终点
- Number of Participants With Serious AEs (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs - Treated Participants
研究概览
简要总结
Multicenter study in which patients with metastatic hormone refractory prostate cancer (HRPC), who have not had previous chemotherapy or immunotherapy treatments, received MDX-010 every 3 weeks for 4 doses (12 weeks total duration of induction). MDX-010 was administered at escalating dosage levels of 3, 5, and 10 mg/kg/dose infusions. At least 6 patients were to be enrolled in each dosage level. Patients who tolerated and responded to treatment or who had stable disease for 3 months or longer and who subsequently progressed during the follow up phase of the study had the option to receive additional treatment with MDX-010, up to 4 cycles. Patients were followed in the study for response up to 2 years and were followed for survival status for up to 5 years after enrollment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologic diagnosis of adenocarcinoma of the prostate
- •Metastatic prostate cancer (positive bone scan or measurable disease)
- •Total testosterone of less than 50 ng/dL, except for patients with prior orchiectomy, where testosterone does not need to be measured.
- •Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen and completion of a washout period and then observe disease progression.
- •Patients must stop using any herbal product known to decrease PSA levels (eg., saw palmetto and PC-SPES) or any systemic or topical corticosteroid at least 4 weeks prior to screening. Progressive disease must be documented after discontinuation of these products.
- •Progressive disease after androgen deprivation (or hormone therapy). For patients with measurable disease, progression will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. For patients with progression in, or without any measurable disease, a positive bone scan and elevated PSA will be required.
- •Patients receiving bisphosphate therapy must have been on stable doses for at least 4 weeks with stable symptoms prior to enrollment.
- •No prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control prostate cancer).
- •Prior radiation therapy completed at least 4 weeks prior to enrollment. No prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment.
排除标准
- •Bone pain due to metastatic bone disease severe enough to require routine narcotic analgesic use.
- •History of severe hypersensitivity reactions to drugs formulated with polysorbate
- •Patients with active autoimmune disease or a history of autoimmune disease that required systemic steroids or immunosuppressive medications, except for patients with vitiligo.
- •Prior therapy with any anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibody.
- •Active infection requiring therapy.
- •Concurrent medical condition requiring the use of systemic or topical corticosteroids; systemic or topical corticosteroids must be discontinued at least 4 weeks prior to enrollment. The use of inhaled corticosteroids is acceptable.
研究组 & 干预措施
MDX-010
干预措施: MDX-010 (Drug)
结局指标
主要结局
Number of Participants With Serious AEs (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs - Treated Participants
时间窗: Day 1 to last day of study treatment (+70 days) up to 2 years
AEs graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. Immune-related AE (irAE) was defined as a clinically significant AE of any organ that is associated with drug exposure, of unknown etiology, and is consistent with an immune-mediated mechanism. Day 1=first day of study treatment.
Number of Participants With Best PSA Response at Day 85 by Category - PSA Evaluable Participants
时间窗: Day 85
Response by investigator using National Cancer Institute (NCI) PSA Working Group recommendations= PSA \< 50% of PSA reference value occurring on or before Day 85; response confirmed at least 4 weeks after the first measurement. PSA reference=PSA measured immediately prior to treatment. Complete response (CR)=PSA \< 2 nanograms per milliliter (ng/mL), confirmed at least 4 weeks after 1st value; Partial response (PR)=PSA ≤ 50% of PSA reference, confirmed at least 4 weeks after 1st value; Unconfirmed=not confirmed by repeat measurements; Stable disease(SD)=No change from PSA reference; Progressive disease (PD) defined: If PSA nadir was ≥ 100% of the reference: PSA ≥ 125% of PSA reference and with a difference of absolute value of ≥ 5 ng/mL; If PSA nadir was \< 100% and ≥ 50% of the reference: PSA ≥ 125% of PSA nadir and with a difference of absolute value of ≥ 5 ng/mL: If PSA nadir was \< 50% of the reference: PSA ≥ 150% of PSA nadir and with a difference of absolute value of ≥ 5 ng/mL.
次要结局
- Number of Participants With Best Overall Tumor Response by Category - Tumor Evaluable Participants(Day 1 to last day of study treatment (+70 days) up to 2 years)
- Time to PSA Response at Day 85 in Participants With Complete Response (CR) or Confirmed Partial Response (PR) at Day 85(Day 1 to Day 85)
- PSA Response Rate at Day 85 and Overall PSA Response Rate in 10 mg/kg Monotherapy and Combination Therapy(Day 85, Day 1 to last day of study treatment (+70 days) up to 2 years)
- Number of Participants With Best Overall PSA Response by Category - PSA Evaluable Participants(Day 1 to last day of study treatment (+70 days) up to 2 years)
- Overall Tumor Response Rate in 10 mg/kg Ipilimumab Monotherapy and Ipilimumab/XRT Combination Therapy(Day 1 to last day of study treatment (+70 days) up to 2 years)
- Number of Participants Who Died by Date of Primary Analysis and by Date of Completion of Follow Up - All Treated Participants(Day 1 to 5 years post treatment)
- Overall Survival at Completion of Follow Up Period - Treated Participants(Day 1 to 5 years post treatment)
- Number of Participants With On-Study Hematology Laboratory Tests Worst Common Terminology Criteria (CTC) Grade - Treated Participants(Day 1 to last day of study treatment (+70 days) up to 2 years)
- Number of Participants With On-Study Serum Chemistry Laboratory Tests Worst Common Terminology Criteria (CTC) Grade - Treated Participants(Day 1 to last day of study treatment (+70 days) up to 2 years)
- Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities at Baseline and During Treatment Period - Treated Participants(Baseline up to 2 years)
- Number of Participants Positive for Human Anti-Human Antibodies (HAHA) - Treated Participants(Day 1 up to 2 years)