NCT06563986招募中2 期
Single-arm, Phase II Trial of Trifluridine/Tipiracil (FTD-TPI), Bevacizumab, and Individualized Radioembolization With 166Ho-microspheres in Refractory Metastatic Colorectal Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- UMC Utrecht
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Hepatic objective response rate (hORR) (PERCIST 1.0)
研究概览
简要总结
Extrahepatic disease progression limits clinical efficacy of individualized radioembolization for patients with refractory metastatic colorectal cancer (mCRC). In the same patient population, trifluridine/tipiracil (FTD-TPI) and bevacizumab lead to disease control and overall survival benefit and may be a radiosensitizer.
The purpose of this study is to determine safety, tolerability, and activity of individualized radioembolization with 166Holmium (166Ho)-microspheres combined with FTD-TPI and bevacizumab.
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
- •Unresectable liver dominant mCRC
- •Prior therapy with fluoropyrimidine, oxaliplatin, and irinotecan for the treatment of metastatic colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen
- •Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be eligible to enter the study.
- •Patients who refuse oxaliplatin or irinotecan will also be eligible to enter the study.
- •Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy count the adjuvant therapy as treatment of metastatic colorectal cancer.
- •Written informed consent
- •Age >=18 years
- •Estimated hepatic tumor replacement ≥ 10% and ≤ 50% of total liver volume Eastern Cooperative Oncology Group performance status 0-1
- •Adequate organ function as measured by: WBC ≥ 3.0 x 109/L, platelets ≥ 100 x 109/L, absolute neutrophil count > 1.5 x 109/L, Hemoglobin (Hb) > 5 mmol/L (>8.1 g/dL), eGFR ≥ 35 ml/min, Serum transaminases (AST & ALT) ≤ 5 x upper limit of normal (ULN), Total bilirubin ≤ ULN, Albumin > 3 g/dL
- •At least one measurable liver lesion according to the PERCIST 1.0
排除标准
- •Significant extrahepatic disease, defined as symptomatic extrahepatic disease, more than 10 pulmonary nodules (maximum diameter of each lung metastasis <20mm), and/or peritoneal carcinomatosis.
- •Eligible for ablative local treatment of liver metastases (e.g. surgical resection, ablation)
- •Lung shunt >20 Gy, as calculated using scout dose SPECT/CT
- •Absorbed tumor dose <90 Gy when dosing at a maximum average absorbed normal liver dose
- •Other malignancy confounding prognosis
- •Receipt of chemotherapy within 28 days prior to study treatment
- •Previous or current treatment with radioembolization
- •Major surgery within 28 days or incompletely healed surgical incision before starting study therapy
- •Any serious comorbidity preventing the safe administration of anti-VEGF antibody treatment. This includes uncontrolled hypertension or treatment with ≥3 antihypertensive drugs, arterial (cerebro)vascular event within the past 6 months, history of severe bleeding, history of GI perforation, or presence of fistulae
- •Any serious and/or chronic liver disease preventing the safe administration of radio- embolization
- •Uncorrectable extrahepatic deposition of scout dose activity; activity in the falciform ligament, portal lymph nodes and gallbladder is accepted
- •Pregnancy or breastfeeding
- •Body weight over 150 kg (because of maximum table load)
- •Known severe allergy for intravenous contrast fluids
- •Participation to another investigational study which may compromise any endpoint of the study
研究组 & 干预措施
Intervention: Systemic treatment (FTD-TPI + bevacizumab) and radioembolization
Experimental
- Individualized dose 166Ho radioembolization, combined with systemic treatment:
- 35 mg/m2 FTD-TPI on day 1-5 and 8-12 every 4 weeks
- 5 mg/kg bevacizumab iv. on day 1 and 15 every 4 weeks
干预措施: Systemic treatment (FTD-TPI and bevacizumab) (Drug)
Intervention: Systemic treatment (FTD-TPI + bevacizumab) and radioembolization
Experimental
- Individualized dose 166Ho radioembolization, combined with systemic treatment:
- 35 mg/m2 FTD-TPI on day 1-5 and 8-12 every 4 weeks
- 5 mg/kg bevacizumab iv. on day 1 and 15 every 4 weeks
干预措施: Radioembolization with 166-Ho microspheres (Device)
结局指标
主要结局
Hepatic objective response rate (hORR) (PERCIST 1.0)
时间窗: Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.
Hepatic objective response rate (hORR) will be assessed by Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0.
次要结局
- Radioembolization completion rate(Evaluated immediately after the radioembolization treatment.)
- Occurrence of radioembolization-induced liver disease (REILD)(Evaluated every 8 weeks after start treatment during the first half year.)
- Dose reductions, dose delays of FTD-TPI(Evaluated during the first two cycles (each cycle is 28 days).)
- Grade ≥3 adverse events (CTCAE 5.0)(Evaluated every 8 weeks after start treatment during the first half year. The collection period will start from the first day of the first treatment cycle until 180 days thereafter.)
- Overall and extra-hepatic ORR (PERCIST 1.0)(Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.)
- Serious adverse events (SAE's)(Evaluated every 8 weeks after start treatment during the first half year. The collection period will start from the first day of the first treatment cycle until 180 days thereafter.)
- Radioembolization related vascular events(Evaluated every 8 weeks after start treatment during the first half year.)
- Progression free survival (PFS)(Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.)
- Overall survival (OS)(Evaluated once per year until the end of the study (the end of study is defined as six months after the first day of the first treatment cycle (each cycle is 28 days) of the 36th evaluable participant).)
- Hepatic objective response rate (hORR) (RECIST 1.1)(Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.)
- Overall and extra-hepatic ORR (RECIST 1.1)(Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.)
研究者
研究点 (1)
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