Phase II Study of Front Line Therapy With Nivolumab and Salvage Nivolumab + Ipilimumab in Patients With Advanced Renal Cell Carcinoma. HCRN: GU16-260
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 164
- 试验地点
- 12
- 主要终点
- 1-year Progression Free Survival (PFS) Rate for ccRCC Patients
研究概览
简要总结
Phase II trial of nivolumab in 120 treatment naïve patients with ccRCC.
详细描述
Eligible patients with biopsiable (biopsied) disease will receive nivolumab 240 mg IV every 2 weeks x 6 doses then 360 mg every 3 weeks for up to 84 weeks. Tumor response will be assessed at weeks 12, 18 and 24 and then every 12 weeks. For patients who experience RECIST 1.1 defined PD, but remain clinically stable (and asymptomatic), a confirmatory scan after 6 weeks (± 1 week) of additional therapy is suggested. Patients with persistent PD at confirmatory scan will be evaluated for enrollment on Part B of this study. Symptomatic patients may be evaluated for Part B immediately. Patients without confirmed PD can continue on nivolumab therapy.
Patients who experience symptomatic or confirmed PD (or have best response of SD at 12 months) on nivolumab monotherapy will be eligible for consideration for Part B. Part B involves the addition of ipilimumab for up to 4 doses while maintaining nivolumab therapy. Dose of ipilimumab will be 1 mg/kg every 3 weeks together with nivolumab changed to 3 mg/kg every 3 weeks for up to 4 doses. Nivolumab will revert to 360 mg every 3 weeks after the completion of treatment with ipilimumab (beginning week 13-19 of Part B) for up to 48 weeks. Patients will be followed with serial imaging assessments weeks 12, 18 and 24 and then every 12 weeks after the initiation of ipilimumab. The tumor measurements at the time of ipilimumab institution will be the new baseline. If unequivocal symptomatic or confirmed new PD (as defined above) develops, treatment will be discontinued.
Patients for Part B must still meet the eligibility criteria for initial study enrollment. Patients with Grade 3 toxicity on nivolumab monotherapy, serious symptomatic disease that in the opinion of the site investigator requires immediate use of an alternative treatment approach or continued PR/CR will be excluded from enrolling in Part B. It is estimated that roughly half of the patients accrued to the first-line treatment will go on to enroll in Part B.
An additional biopsy will be performed of a metastatic lesion at time of confirmed PD in all patients enrolling in Part B. Confirmation of tumor in the biopsy specimen must occur prior to initiation of treatment on Part B. FFPE and frozen tissue will be stored from this sample and used for correlative studies described below.
An additional cohort of 40 non-ccRCC patients will be enrolled and analyzed separately for evidence of anti-tumor activity (CR, PR and SD and PFS at 1 year of nivolumab). These patients will also be eligible for participation in Part B. We anticipate that the accrual of these 40 patients will be able to be completed within the 1.5 years needed for accrual of the ccRCC patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for 2 weeks of more after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
- •Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected without recurrence or treated with SRS without progression x 4 weeks.
- •Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- •Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- •As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
- •Active infection requiring systemic therapy
- •Has any other medical or personal condition that, in the opinion of the site investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's successful completion of the clinical trial
- •Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
- •Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- •Allergies and Adverse Drug Reaction
- •History of allergy to study drug components
- •History of severe hypersensitivity reaction to any monoclonal antibody
- •Known additional malignancies within the past 3 years (excluding basal of squamous cell skin cancers, CIS or localized prostate cancer that has been treated or is being observed)
- •Inclusion/Exclusion Criteria- Part B
- •Must meet eligibility criteria for initiation of Part A with the exception of being allowed to have prior nivolumab in Part A of this protocol
- •Must have evidence of either RECIST 1.1 defined Disease Progression or Stable Disease 1 year after initiating nivolumab therapy
- •Tumor biopsy prior to combination treatment is mandatory. If a biopsy/resection of a new lesion or primary tumor and slow freezing of fresh tissue for single cell RNAseq study (as specified in the CLM) is not feasible, the subject is not eligible for the study. All biopsies must be core needle or excisional. Fine needle aspirate is not acceptable.
- •Must not have had a Grade ≥ 3 irAE on nivolumab monotherapy
- •Must not have untreated brain metastases
- •Must not have had major surgery or radiation therapy within 14 days of starting study treatment
- •Must not have active autoimmune disease
- •Must not have a concurrent medical condition requiring use of systemic corticosteroids with prednisone >10 mg per day
- •Must not have had prior systemic therapy for Stage IV RCC (except for nivolumab as part of part A of this protocol)
- •Prior solid organ or stem cell transplant
研究组 & 干预措施
PART A: Nivolumab
Nivolumab 240mg; Nivolumab 360mg
干预措施: Nivolumab 240 mg (Drug)
PART A: Nivolumab
Nivolumab 240mg; Nivolumab 360mg
干预措施: Nivolumab 360mg (Drug)
PART B: Nivolumab + Ipilimumab
Nivolumab 3mg/kg and Ipilimumab 1mg/kg; Nivolumab 360mg
干预措施: Ipilimumab 1mg/kg (Drug)
PART B: Nivolumab + Ipilimumab
Nivolumab 3mg/kg and Ipilimumab 1mg/kg; Nivolumab 360mg
干预措施: Nivolumab 3mg/kg (Drug)
PART B: Nivolumab + Ipilimumab
Nivolumab 3mg/kg and Ipilimumab 1mg/kg; Nivolumab 360mg
干预措施: Nivolumab 360mg (Drug)
结局指标
主要结局
1-year Progression Free Survival (PFS) Rate for ccRCC Patients
时间窗: 1 year
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. 1-year Progression-Free Survival (PFS) Rate refers to the percentage of patients who have not experienced disease progression or death from any cause within one year of starting treatment. The 1-year PFS rate of nivolumab in treatment-naïve patients with clear cell renal cell carcinoma (ccRCC) was assessed according to tumor PD-L1 expression levels.
次要结局
- Objective Response Rate for ccRCC Patients Treated With Nivolumab Monotherapy(Up to 39 Months)
- Clinical Activity for nccRCC Patients(Up to 39 Months)
- Objective Response Rate (ORR) for ccRCC Patients Treated With Nivolumab and Ipilimumab(Up to 39 Months)
- 1-year Progression Free Survival (PFS) Rate for nccRCC Patients(1 year)
- Number of Participants With Adverse Events(Up to 28 months)
研究者
Michael B. Atkins, MD
Sponsor-Investigator
Hoosier Cancer Research Network