A Prospective Phase II Single-Arm Trial on Neoadjuvant Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE Followed by Surgery for Resectable Pancreatic Neuroendocrine Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Postoperative morbidity
研究概览
简要总结
Peptide Receptor Radionuclide Therapy (PRRT) is based on specific somatostatin receptor targeting with radiolabelled analogues 90Y-DOTATOC and 177Lu-DOTATATE. These two most commonly used radiopeptides, 90Y-DOTATOC and 177Lu-DOTATATE, produce overall objective response rates of 15-35%. PRRT is generally well tolerated with mild toxicity, if the necessary precautions, such as the co-administration of nephroprotective amino acids or the adjustment of the administered activity, are taken.
The main aim of this study is to evaluate the safety and the efficacy of neoadjuvant PRRT with 177Lu-DOTATATE followed by surgical resection for resectable non-functioning PanNETs at high risk of recurrence.
The primary endpoint is the Rate of postoperative 90-day morbidity and mortality after neoadjuvant PRRT with 177Lu-DOTATATE followed by pancreatic resection and the secondary endpoints are:
- Rate of objective radiological response to PRRT with 177Lu-DOTATATE according to RECIST criteria (version 1.1), for primary lesions' assessment, and modified RECIST criteria (mRECIST), for liver metastases' assessment, if detected
- Quality of life (QoL) after neoadjuvant PRRT followed by pancreatic surgical resection.
The study is designed as a prospective phase II single-arm trial. 8 Italian centers will participate to the study (6 surgical sites, 2 nuclear medicine sites).
Patients will be recruited for 12 months. The study will end 2 months after operation of the last patient enrolled and the total duration of the study will be 24 months.
Sample size estimation: 30 patients
详细描述
Rationale:
In a recent study un initial experience was reported with neoadjuvant PRRT followed by surgical resection in patients affected by PanNETs. In this study, patients with resectable or potentially resectable PanNETs at high risk of recurrence after surgery who underwent neoadjuvant PRRT were compared with a group of patients who underwent upfront surgery. Of note, patients who underwent neoadjuvant PRRT had a significant lower risk of developing pancreatic fistula and a lower risk of postoperative complications. Moreover, among those patients who underwent curative resection, patients who received PRRT had a progression-free survival significantly longer after compared to upfront surgery. Neoadjuvant PRRT may be a valuable option to reduce the risk of failure after surgery in patients with PanNETs who are at high risk of recurrence. Nevertheless, the safety and the efficacy of neoadjuvant PRRT has never been investigated in a prospective trial.
The main aim of this study is to evaluate the safety and the efficacy of neoadjuvant PRRT with 177Lu-DOTATATE followed by surgical resection for resectable non-functioning PanNETs at high risk of recurrence.
The primary endpoint is the Rate of postoperative 90-day morbidity and mortality after neoadjuvant PRRT with 177Lu-DOTATATE followed by pancreatic resection and the secondary endpoints are:
- Rate of objective radiological response to PRRT with 177Lu-DOTATATE according to RECIST criteria (version 1.1), for primary lesions' assessment, and modified RECIST criteria (mRECIST), for liver metastases' assessment, if detected.
- Quality of life (QoL) after neoadjuvant PRRT followed by pancreatic surgical resection.
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
- •Morphological confirmation by high-quality imaging technique (MR or CT scan)
- •Cytological or histologically confirmed sporadic resectable nonfunctioning PanNETs (NF-PanNETs) with positive 68Ga-DOTATOC PET/CT (with primary lesion uptake greater than the normal liver and SUV bw max ≥ 15) and at least one of the following high-risk features:
- •Radiological tumour size > 40 mm
- •Well differentiated G2 NF-PanNETs with Ki67 >10% or well differentiated NF-PanNETs G3
- •Presence of nearby organs involvement
- •Vascular invasion (excluding the presence of superior mesenteric vein/portal vein invasion > 180° and/or celiac trunk/superior mesenteric artery invasion)
- •Mesenteric and/or portal and/or splenic vein thrombosis
- •Presence of a single resectable liver metastasis
- •Presence of enlarged hypervascularized lymph nodes at imaging that are positive at 68Ga-DOTATOC PET/CT
- •Absence of extra-abdominal disease
- •Absence of peritoneal carcinomatosis
- •Karnofsky Performance Status ≥ 90 or o ECOG-PS=0
- •Preserved hematologic, hepatic and renal parameters (WBC> 2,500/ml [ANC> 1,500/mcl]; Hb> 10g/dL; PTL> 100,000/mcl; bilirubin< 2.5 mg/dl, creatinine< 2 mg/dl)
- •Absence of serious disease which can compromise safety (cardiac failure, previous myocardial infarction within prior 6 months, history of psychiatric disabilities, synchronous malignancy)
排除标准
- •Age < 18 years
- •Negative functional Imaging (68Ga-DOTATOC PET/CT)
- •Presence of genetic syndrome (MEN1, VHL, NF)
- •Functioning PanNET
- •NF-PanNEC G3
- •Absence of "high-risk features" as defined above
- •Presence of extra abdominal disease
- •Presence of multiple liver metastases
- •Presence of peritoneal carcinomatosis
- •Previous PanNET-directed treatment
- •Karnofsky Performance Status < 90% or ECOG-PS > 0
- •Inadequate bone marrow, liver and kidney function
- •Presence of serious disease which can compromise safety (cardiac failure, previous myocardial infarction within prior 6 months, history of psychiatric disabilities, synchronous malignancy)
- •Bone marrow invasion
- •Life expectancy less than 6 months
- •Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
- •Known or suspected non-compliance, drug or alcohol abuse
- •Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
- •Participation in another study with investigational drug within the 30 days preceding and during the present study or 5 half-life of the experimental drug
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
- •Creatinine clearance < 30 mL/min calculated by the Cockroft Gault method
- •Uncontrolled congestive heart failure (NYHA III, IV).
- •Total bilirubin > 3 x normal rate
- •Serum albumin < 3.0 g/dL u
- •Hb concentration < 5.0 mmol/L (<8.0 g/dL); WBC < 2x10E9/L (2000/mm3); platelets < 75x10E9/L (75x10E3/mm3)
- •Pregnancy or lactation
研究组 & 干预措施
All enrolled patients
Enrolled patients following inclusion criteria
干预措施: 177Lu-Dotatate (Drug)
结局指标
主要结局
Postoperative morbidity
时间窗: from week 40 until week 52
Rate of postoperative 90-day morbidity after neoadjuvant PRRT with 177Lu-DOTATATE followed by pancreatic resection
Postoperative mortality
时间窗: from week 40 until week 52
Rate of postoperative 90-day mortality after neoadjuvant PRRT with 177Lu-DOTATATE followed by pancreatic resection
次要结局
- Radiological response(week 38)
研究者
Massimo Falconi
Professor
IRCCS San Raffaele