PRIME-LRT: PRomoting IMmunotherapy Efficacy With Low-Dose Liver RT
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Progression free survival (PFS) measured by 6-month PFS for each cohort compared separately to historical trials with an effect size goal of 25% improvement in 6-month PFS
研究概览
简要总结
The purpose of this study is to see if adding Low-Dose Liver Radiation (LD-LRT) improves progression free survival (PFS). This study is for patients with either melanoma or non-small cell lung cancer (NSCLC), with liver metastases, and receiving immunotherapy.
详细描述
Patients will continue standard of care immunotherapy (with or without standard chemotherapy). The research aspect of this study will be adding in the Low-Dose Liver Radiation (LD-LRT) before cycles 1, 2, 3 of treatment to see if this improves the treatment effects.
The trial will be conducted using Simon's optimal two-stage test in two separate cohorts. Cohort 1 will include patients with NSCLC with liver metastases. Cohort 2 will include patients with melanoma with liver metastases. The primary endpoint is 6-month PFS for each cohort compared separately to historical trials with an effect size goal of 25% improvement in 6-month PFS.
Cohort 1 NSCLC- The estimated 6-month PFS in NSCLC with liver metastasis was obtained from a metanalysis of 8 randomized trials evaluating the effect of liver metastases in patients treated with PD-1/PD-L1 inhibitors and chemotherapy (SOC) or chemotherapy alone[30]. Based on the pooled hazard ratios we estimate a 0.68 HR and PFS of 30% at 6 months with chemotherapy alone. Assuming underlining exponential distribution for survival time, we estimate the 6-month PFS is 44% in patients with liver metastases treated with PD-1/PD-L1 inhibitors and chemotherapy.
Simon's optimal two-stage design (Simon, 1989) will be used for conducting the trial. In cohort 1, the null hypothesis is that the true response rate (6-month PFS) is 0.44, and the alternative hypothesis is that the true response rate is 0.69. The trial is carried out in two stages. In stage I, a total number of 11 patients is accrued. If there are 5 or fewer responses among these 11 patients, cohort 1 will be stopped. Otherwise, an additional 15 patients will be accrued in stage II, resulting in a total number sample size of 26. If there are 16 or more responses among these 26 patients, we reject the null hypothesis and claim that the treatment is promising. The design controls the type I error rate at 0.049 and yields the power of 0.81. The probability of early termination is 66%.
Cohort 2 Melanoma with liver met (Expected 6-mo PFS= 30%, Desired 6-mo PFS=55%) The null hypothesis for 6-month PFS of 30%, based on historic clinical trials and series specifically evaluating PFS in patients with melanoma and liver metastases treated with standard of care immunotherapy[9-11, 14]. The alternative hypothesis is that the 6-month PFS is 55%. The trial is carried out in two stages. In stage I, a total number of 10 patients is accrued. If there are 3 or fewer responses among these 10 patients, the cohort will be closed. Otherwise, an additional 18 patients will be accrued in stage II for cohort 2, resulting in a total sample size of 28 patients. If there are 13 or more responses among these 28 patients, we reject the null hypothesis and claim that the treatment is promising. The design controls the type I error rate at 0.05 and yields the power of 0.8. The probability of early termination is 65%.
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
- •Age ≥18 years.
- •ECOG performance status ≤2 (or Karnofsky ≥60%, see Appendix A).
- •Patients must have adequate organ and marrow function to receive standard of care immunotherapy and/or chemoimmunotherapy as per the treating medical oncologist.
- •Must be planning to, and able to, undergo active treatment with PD-L1 or PD-1 checkpoint immunotherapy given per standard care throughout the duration of the RT intervention per their treating physician.
- •Note: Patients may receive other SOC CTLA 4 inhibitors or other SOC chemotherapy/immunotherapy in combination with a SOC PD-L1 or PD-1 checkpoint inhibitor and remain eligible.
- •Biopsy proven Non-Small Cell Lung Cancer (NSCLC) or Melanoma.
- •Radiographic evidence of liver metastases.
- •Women of child-bearing potential and men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
- •Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
- •Patients must have insurance authorization to proceed with radiotherapy prior to initiation of radiation treatment on study
排除标准
- •Patients with prior immunotherapy use in the adjuvant setting for NSCLC or Melanoma are eligible unless the adjuvant immunotherapy was delivered within 6 months of enrollment.
- •Patients with NSCLC are ineligible for enrollment in cohort 1 if the presence of the following driver mutations are noted: EGFR, ALK, ROS1, RET.
- •Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous, in the opinion of the Investigator.
- •Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the Investigator.
- •Pregnant women are excluded from this study considering the use of ionizing radiation.
研究组 & 干预措施
LD-LRT
Low-dose radiation to the liver the week prior to Cycles 1, 2 and 3 of systemic treatment.
干预措施: LD-LRT (Radiation)
结局指标
主要结局
Progression free survival (PFS) measured by 6-month PFS for each cohort compared separately to historical trials with an effect size goal of 25% improvement in 6-month PFS
时间窗: 6 months
The primary objective is to evaluate whether the addition of Low-Dose Liver Radiation (LD-LRT) improves progression free survival (PFS) in patients with melanoma and non-small cell lung cancer (NSCLC) with liver metastases receiving immunotherapy. The primary endpoint is 6-month PFS for each cohort compared separately to historical trials with an effect size goal of 25% improvement in 6-month PFS.
次要结局
- Overall survival (OS) measured by time to death or last follow up(Enrollment to death or last follow-up (up to 2.5 years))
研究者
Jordan Kharofa
Principal Investigator
University of Cincinnati