Preoperative PRRT Versus Surgical Cytoreduction Alone in Metastatic Pancreatic Neuroendocrine Tumors to the Liver: A Phase II Multi-institutional Trial
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Progression-free Survival
研究概览
简要总结
Doctors and researchers leading this study hope to learn more about peptide receptor radionuclide therapy (PRRT) in combination with cytoreduction (surgically removing tumors). They hope to learn if combining PRRT in combination with cytoreduction would be more effective than cytoreduction alone. PRRT itself is approved by the U.S. Food and Drug Administration (FDA) for people with PanNETs however the combination with cytoreduction is considered experimental.
Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT.
详细描述
Doctors and researchers leading this study hope to learn more about peptide receptor radionuclide therapy (PRRT) in combination with cytoreduction (surgically removing tumors). They hope to learn if combining PRRT in combination with cytoreduction would be more effective than cytoreduction alone. PRRT itself is approved by the U.S. Food and Drug Administration (FDA) for people with PanNETs however the combination with cytoreduction is considered experimental.
Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT.
PRRT is a form of targeted treatment (think of a "lock and key") done by the use of a small molecule (Lutathera) Lutathera acts as a "key" to "lock" onto certain areas your tumor cells called receptors when injected into a vein and travels through the bloodstream. Lutetium-177 is the radionuclide in Lutathera which is a chemical that delivers strong radiation directly into your tumor cells and works by causing death of the cancerous tissues.
PRRT can only be done on patients who have tumors that have the somatostatin receptors. Before being given PRRT, your treating doctor will run imaging tests to make sure your tumors have these targeted receptors. Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT.
Participants will be randomized (like the flip of a coin) to one of two arms. Arm 1 is the control arm, which will undergo standard of care cytoreductive surgery (for the tumor). Arm 2 will undergo four cycles of PRRT before cytoreductive surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Metastatic Pancreatic neuroendocrine tumors (PanNET) to the liver
- •Well- or moderately differentiated (grade 1 or grade 2, Ki-
- •Ability to aim for equal or greater than 90% hepatic cytoreduction surgically
- •Proof of SSTR2 expression by uptake of tumor on 68Ga DOTATATE PET CT (Krenning Score on all or a majority of lesions
- •Age older than 18 years
- •No Somatostatin Analogues (SSA) or other systemic therapy for 4 weeks prior to starting PRRT, if randomized to arm 2.
排除标准
- •Patient with G3 or poorly differentiated NET (grade 3, Ki-67 >20%)
- •Previous liver-directed therapy with Yttrium-90 (TACE/TAE allowed if performed more than 12 months prior to enrollment)
- •Systemic therapy with Capecitabine and/or Temozolamide within 12 months of enrollment.
- •No tumor uptake on 68Ga DOTATATE PET CT
- •Liver tumor burden > 50% (as defined by CT or MRI)
- •Signs of early liver failure (T-Bilirubin >3, INR > 1.5, Albumin <3.0 g/dL unless prothrombin time is within the normal range) or cirrhosis or ascites
- •calculated by the Cockroft Gault method, eventually confirmed by measured creatinine clearance
- •(or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma
- •camera-based) <50 mL/min (the measured creatinine clearance / GFR is required only as - confirmatory exam).
- •Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L (2000/mm3); platelets <75x109/L - (75x103/mm3).
- •Known brain metastases, unless these metastases have been treated and stabilized.
- •Uncontrolled congestive heart failure (NYHA II, III, IV).
- •Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
- •Pregnancy or lactation.
- •For female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male patients, who are not surgically sterile or with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel). - Prior external beam radiation therapy to more than 25% of the bone marrow.
- •Current spontaneous urinary incontinence making impossible the safe administration of the radioactive IMP.
- •Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and with no evidence of recurrence.
- •Patients who have not provided a signed informed consent form to accept this treatment.
- •Poor renal function
- •Quality Unit language added
- •editorial changes
研究组 & 干预措施
Arm 1- Control Arm - Standard Of Care - no peptide receptor radionuclide therapy
Arm 1 is the control arm, which will undergo standard of care cytoreductive surgery (for the tumor). Participants in this arm will not receive peptide receptor radionuclide therapy (PRRT).
干预措施: cytoreductive surgery (Procedure)
Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)
Arm 2 will undergo four cycles of peptide receptor radionuclide therapy (PRRT) before cytoreductive surgery.
干预措施: cytoreductive surgery (Procedure)
Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)
Arm 2 will undergo four cycles of peptide receptor radionuclide therapy (PRRT) before cytoreductive surgery.
干预措施: Lutathera - a small molecule used in Peptide Receptor Radionuclide Therapy (PRRT) (Drug)
Arm 2 (peptide receptor radionuclide therapy + cytoreductive surgery)
Arm 2 will undergo four cycles of peptide receptor radionuclide therapy (PRRT) before cytoreductive surgery.
干预措施: Peptide receptor radionuclide therapy (PRRT) (Procedure)
结局指标
主要结局
Progression-free Survival
时间窗: 2 years
To determine whether preoperative peptide receptor radionuclide therapy (PRRT) prior to hepatic cytoreduction increases progression free survival (PFS1) (when compared to cytoreduction alone) in patients with metastatic PanNETs to the liver
次要结局
- Objective Response Rate(2 Years)
- Overall Survival(2 years)
- Improvement in Overall Survival(2 years)
- Difference in imaging characteristics(2 years)
- Increase in Progression Free Survival(2 years)
- Improvement in Progression-Free Survival (PFS2)(2 years)