Combination Radiation and PD-1 Inhibition in Metastatic or Recurrent RCC
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
There are two primary aims in the study: 1) to determine the tolerability and feasibility of combination hypofractionated radiation therapy and PD-1 inhibition with nivolumab, and 2) to determine the ability of hypofractionated radiation therapy to enhance response rate from PD-1 inhibition versus PD-1 inhibition alone by comparing the observed response rate under the combination therapy with a previously reported response rate under inhibition alone.
详细描述
Patients with metastatic or recurrent renal cell cancer who have progressed on standard Tyrosine Kinase Inhibitor (TKI) therapy and who have metastatic or primary tumors suitable for palliative radiation will be eligible for this study. Treatment will consist of nivolumab plus hypofractionated radiation therapy. The primary endpoint will be objective response rate, which will be compared against the historical control of 25% using nivolumab alone as established in the CHECKMATE 025 clinical trial. Patients will continue on nivolumab until disease progression or withdrawal of consent. Follow-up will continue for 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed history of renal cell carcinoma (all variants are acceptable)
- •Progression or recurrence after at least one prior tyrosine kinase inhibitor therapy including, but not limited to: sunitinib, pazopanib, axitinib.
- •At least 1 site (primary or metastasis) amenable to hypofractionated radiation therapy and appropriate for radiation therapy as part of standard of care per medical, urologic or radiation oncologist discretion. NOTE: CT / MRI imaging to have been completed no more than 30 days before enrollment on study.
- •Potential indications for radiation therapy include (but are not limited to):
- •Painful bone or soft tissue metastasis
- •Symptoms from mass effect caused by tumor
- •Prevention of impending symptoms from tumor
- •Hemoptysis due to tumor
- •Limited oligometastasis
- •Isolated region of progression
- •Patients with prior IL-2 treatment are eligible
- •At least 14 days since any prior therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3
- •Adequate organ and marrow function as defined below:
- •leukocytes ≥ 2,000/mcL
- •absolute neutrophil count ≥ 1,000/mcL
- •platelets ≥ 100,000/mcL
- •total bilirubin within normal institutional limits
- •AST(SGOT) ≤ 2.5 X institutional upper limit of normal
- •ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
- •Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception. Men of child-bearing potential must not donate sperm while on this study and for 90 days after their last study treatment.
排除标准
- •Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
- •Men who are trying to father a child.
- •Presence of a condition or abnormality that in the opinion of the study-delegated investigator would compromise the safety of the patient or the quality of the data.
- •Requirement for high dose steroids: dexamethasone > 2 mg per day or equivalent
- •NOTE: Per OPDIVO (Nivolumab) package insert, no formal pharmacokinetic drug-drug interaction studies have been conducted with OPDIVO (Nivolumab) - therefore, no other concomitant medications will exclude potential participants.
- •Life expectancy < 6 months.
- •Other active malignancy (patients with no evidence of disease (NED) or are in remission are eligible).
- •Patient has untreated brain metastases. Patients are eligible after documented stable or improved brain metastases at least 1 month after treatment of brain metastases.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD-1 Inhibitors used in study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients with active, known or suspected autoimmune disease (not including type 1 diabetes mellitus, hypothyroidism, skin disorders not requiring systemic treatment or conditions not expected to recur).
- •Patients with interstitial lung disease
- •Patients receiving concurrent other cancer-directed therapy including, but not limited to, Tyrosine Kinase Inhibitor (TKI), Mammalian Target Of Rapamycin (mTOR) inhibition and/or chemotherapy.
研究组 & 干预措施
Nivolumab plus radiation
Nivolumab plus radiation
干预措施: Nivolumab (Drug)
Nivolumab plus radiation
Nivolumab plus radiation
干预措施: Radiation (Radiation)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Every 3 months up to 2 years or progression
Objective response rate (ORR) defined as the sum of partial response (PR) and complete response (CR). Timeframe will be best response from registration to end of treatment.
次要结局
- ORR at irradiated sites(Every 3 months up to 2 years or progression)
- Progression free survival (PFS)(12 months)
- ORR at un-irradiated sites(Every 3 months up to 2 years or progression)