Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma: A Multicenter Phase II Trial (The STRONG 2 Trial)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 11
- 主要终点
- Local tumor control
研究概览
简要总结
The objective of this study is to evaluate the efficacy of stereotactic body radiation therapy (SBRT) as additional treatment after standard chemotherapy regarding tumor local control, toxicity, progression-free survival (PFS), overall survival and quality of life. In addition, the objective is to explore the value of immunodynamics in peripheral blood for predicting PFS in patients undergoing chemotherapy.
详细描述
Rationale:
For patients with perihilar cholangiocarcinoma, surgery is the only treatment modality that can result in cure. Unfortunately, in the majority of these patients the tumors are found to be unresectable at presentation due to local invasive tumor growth or the presence of distal metastases. For patients with unresectable cholangiocarcinoma, palliative chemotherapy is the standard treatment, yielding an estimated median overall survival of 12-15.2 months.
There is no evidence from randomized trials that support the routine use of stereotactic body radiation therapy (SBRT) for cholangiocarcinoma. The STRONG phase I feasibility study showed favorable outcomes regarding safety, and the therapy was generally well tolerated. Based upon these observations, a phase II multi-center study with SBRT after chemotherapy in patients with unresectable perihilar cholangiocarcinoma is proposed, in order to further research the efficacy of adding SBRT to standard chemotherapy.
In addition, an explorative translational research component is part of the study, in which peripheral immunodynamics, specifically myeloid nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB) signaling and interferon-stimulated genes (ISG) responses within the myeloid cells, may help to predict survival after chemotherapy and may also help to predict the value of additional treatment with radiotherapy.
Objective:
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
- •translational part of the study:
- •In order to be eligible to participate in the translational part of the study, a subject must be discussed in a liver tumor board, should be eligible for gemcitabine-based chemotherapy (and immunotherapy, if applicable), and should meet all of the following criteria pre-chemotherapy:
- •Perihilar cholangiocarcinoma (pCCA) according to the criteria of the Mayo Clinic, Rochester: a positive or strongly suspicious intraluminal brush cytology or biopsy, or a radiographic malignant appearing stricture plus either: CA 19-9>100 U/ml in the absence of acute bacterial cholangitis, or polysomy on fluorescence in situ hybridization (FISH), or a well-defined mass on cross sectional imaging
- •One tumor mass
- •Unresectable tumor or patient deemed unfit for surgery
- •T1-T4 (AJCC staging 8th edition), N0-N2-M0 (AJCC staging 8th edition), radiologically or pathologically suspect. N1 is defined as one to three affected lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. N2 is defined as four or more affected lymph nodes from the sites described for N
- •Endoscopic ultrasound (EUS) is leading in identifying pathological lymph nodes compared to CT.
- •In case of (underlying) liver cirrhosis: Child-Pugh A
- •Age ≥ 18 years
- •ECOG performance status 0-1
- •Written informed consent for the translational part of the study
- •Inclusion criteria SBRT part of the study:
- •In addition to the criteria mentioned above, patients should meet the following criteria to be eligible for the treatment with SBRT:
- •Measurable disease to be selected as a target on a computed tomography (CT) or magnetic resonance imaging (MRI) scan, according to RECIST 1.1 criteria
- •Finished gemcitabine-based chemotherapy treatment, preferably 8 cycles. If less cycles are given, patients are still eligible for this study
- •Bilirubin ≤3.0 times normal value, aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤5 times ULN
- •Platelets ≥ 50x10E9/ l, Leukocytes > 1.5x10E9/l, Hemoglobin (Hb) > 6 mmol/l
- •Willing and able to comply to the follow-up schedule
- •Able to start SBRT within 12 weeks after completion of chemotherapy and immuno-therapy (if applicable)
- •Written informed consent for the SBRT part of the study
排除标准
- •translational part of the study:
- •Prior surgery or transplantation of the liver
- •Tumor extension in stomach, colon, duodenum, pancreas or abdominal wall
- •Prior radiotherapy to the liver
- •Current pregnancy
- •Affected lymph nodes outside the regions described in the inclusion criteria
- •Exclusion criteria SBRT part of the study:
- •Progression (local or distant) during or after chemotherapy
研究组 & 干预措施
Stereotactic body radiation therapy
Single-arm study
干预措施: Stereotactic body radiation therapy (Radiation)
结局指标
主要结局
Local tumor control
时间窗: 42 months (maximum follow-up time)
Local tumor control is defined as time from inclusion to local radiological progression. Definition of progression is based on response evaluation criteria in solid tumors (RECIST) 1.1. In RECIST 1.1, response of a tumor to treatment is defined as either complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).
次要结局
- Progression-free survival (PFS)(42 months (maximum follow-up time))
- Overall survival (OS)(42 months (maximum follow-up time))
- Adverse events(42 months (maximum follow-up time))
- Biliary stent-related events (SRE)(42 months (maximum follow-up time))
- Quality of life (QoL) - EQ-5D-5L(36 months)
- Quality of life (QoL) - QLQ-C30(36 months)
- Quality of life (QoL) - QLQ-BIL21(36 months)
研究者
Alejandra Mendez Romero
Principal Investigator
Erasmus Medical Center