Efficacy and Safety of Combining Intestinal Low Dose Radiotherapy and PD-1/PD-L1 Inhibitors for Metastatic Malignant Solid Tumors After Acquired Resistance to Anti-PD1/PD-L1 Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Preclinical and clinical studies have shown that intestinal low dose radiotherapy (ILDR) can enhance antitumor immunity and response to immune checkpoint blockade (ICB). Therefore, the investigators launch a phase Ⅱ trial to evaluate the clinical value of combining ILDR and programmed cell death-1/ -ligand 1 (PD-1/PD-L1) inhibitors in patients with ICB refractory metastatic solid tumor.
This study is designed as a researcher-initiated, two-stage and prospective clinical trial. The target population is patients with advanced metastatic malignant solid tumors who have progressed after immunotherapy. The primary endpoints include objective response rate (ORR), disease control rate (DCR), progression free survival while receiving ILDR combined therapy (PFS2), and lesion-based abscopal response rate. The secondary endpoints include incidence of adverse events (AEs), cancer-specific survival (CSS), and overall response rate (OS).
Sixteen subjects will be enrolled in this trial. The primary objective is to evaluate the safety and efficacy of 1Gy ILDR combined with PD-1/PD-L1 inhibitors in immune-resistant metastatic malignant solid tumors, and biomarker exploration for response prediction.
Eligible patients will be subjected to 1Gy ILDR. Tumor response will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as well as Immune related RECIST (iRECSIST). The extent or severity of adverse reactions will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0). Furthermore, tissue samples, stool samples, and peripheral blood samples will be collected for biomarker exploration.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years, ≤80 years, regardless of gender.
- •ECOG level 0-
- •Expected life span>3 months.
- •At least one accessible and measurable lesion should be selected as the target lesion for observation according to RECIST criteria.
- •Patients with metastatic solid tumors (of any histology) without standard therapy options, who have previously received immunotherapy, immunotherapy combined with chemotherapy, or immunotherapy combined with anti-angiogenesis treatment and have shown disease progression.
- •The patient is considered ineligible for surgical treatment.
- •Patients with brain metastases assessed as clinically stable after treatment through repeated CT and/or MRI scans are eligible.
- •Patients have complete clinical and pathological information.
- •Any psychological, family, social or geographical conditions may hinder compliance with the research protocol.
- •Patients are able to understand the informed consent form, voluntarily participate, and sign the informed consent form.
- •Other indicators accord with the general inclusion criteria for clinical trials.
排除标准
- •Patients with contraindications to radiation therapy and immunotherapy.
- •Previous occurrence of unacceptable immune related toxic side effects (immune myocarditis, pneumonia, etc.).
- •Patients who were assessed as hyperprogressive disease (HPD).
- •Patients who have received pelvic and abdominal radiation therapy within 6 months prior to enrollment.
- •The adverse reactions from prior treatment have not yet recovered to a CTCAE5.0 rating of ≤ 1 (excluding toxicity that has been determined to be risk-free, such as fatigue or hair loss).
- •Accompanied by severe infections.
- •Serious liver disease (such as cirrhosis), kidney disease, respiratory disease, or chronic system diseases such as uncontrollable diabetes and hypertension; Patients who cannot tolerate radiation therapy.
- •Clinical symptoms of brain metastases or meningeal metastasis.
- •The patients with known allergies or allergies to the test drug ingredients.
- •Substance/alcohol abuse.
- •Patients who are pregnant or planning to.
- •Patients participating in other clinical studies that may affect the efficacy/safety of this clinical study.
- •Patients who have undergone major surgical procedures within 30 days.
- •Patients who have received antibiotics, antifungal drugs, antiviral, antiparasitic drugs, or probiotics within 4 weeks.
研究组 & 干预措施
ILDR
1Gy/1F ILDR + PD-1/PD-L1 inhibitors.
干预措施: Intestinal Low Dose Radiotherapy-1Gy (Radiation)
ILDR
1Gy/1F ILDR + PD-1/PD-L1 inhibitors.
干预措施: PD-1/PD-L1 Inhibitors (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 6, 12, 24 weeks after start of ILDR.
The objective effective rate of ILDR combined with PD-1/PD-L1 inhibitors in patients with metastatic malignant solid tumors after acquired resistance to immunotherapy, including complete response and partial response.
Disease Control Rate（DCR）
时间窗: 6, 12, 24 weeks after start of ILDR.
The proportion of patients with optimal response to ILDR combined with PD-1/PD-L1 inhibitors.
Progression Free Survival while Receiving ILDR combined Therapy (PFS2)
时间窗: 6, 12, 24 weeks after start of ILDR.
The time from the date of ILDR initiation to the documented disease progression or death due to cancer.
Lesion-based Abscopal Response Rate
时间窗: 6, 12, 24 weeks after start of ILDR.
The proportion of patients with tumor objective response in one or more lesions.
Progression Free Survival while Receiving ILDR combined Therapy (PFS)
时间窗: 6, 12, 24 weeks after start of ILDR.
The time from the date of ILDR initiation to the documented disease progression or death due to cancer.
次要结局
- Incidence of Adverse Events(12, 24, 48 weeks after start of ILDR.)
- Overall survival (OS)(24, 48 weeks after start of ILDR.)
- Cancer-specific survival (CSS)(24, 48 weeks after start of ILDR.)
研究者
Chuangzhen Chen
Dr
Shantou University Medical College