This phase II trial compares peptide receptor nucleotide therapy (PRRT) before surgery (preoperative) versus surgery alone in treating patients with pancreatic neuroendocrine tumors that have spread from where they first started (primary site) to the liver (metastatic). 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 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 the tumor cells and works by causing death of the cancerous tissues. Giving PRRT before surgery might increase the time it takes for the tumor to come back when compared with surgery alone.
Additional locations may be listed on ClinicalTrials.gov for NCT05610826.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To determine whether preoperative PRRT prior to hepatic cytoreduction increases progression free survival (PFS1) (when compared to cytoreduction alone) in patients with metastatic pancreatic neuroendocrine tumors (PanNETs) to the liver.
SECONDARY OBJECTIVES:
I. To determine whether preoperative PRRT prior to hepatic cytoreduction increases overall survival (when compared to cytoreduction alone) in patients with metastatic PanNETs to the liver.
II. To determine whether preoperative PRRT induces a significant objective response rate (according to Response Evaluation Criteria in Solid Tumors [RECIST]) in the primary tumor (if available) and hepatic metastases of patients with metastatic PanNETs to the liver, thus facilitating surgical resection.
III. To determine whether PRRT plus cytoreductive surgery increases PFS when compared to a historical cohort of patients undergoing PRRT only for metastatic PanNETs.
IV. To determine whether PRRT + cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves progression-free survival (PFS2) and overall survival (OS).
V. To determine differences in imaging characteristics (e.g. tumor size), biochemical and molecular signatures of patients having received surgery + PRRT or surgery alone.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients undergo standard of care (SOC) cytoreductive surgery on day 0. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) during screening (day -60 to -1), weeks 12 and 24, then every 12 weeks until progressive disease (PD), and gallium Ga 68-DOTATATE positron emission tomography/computed tomography (PET/CT) during screening and at week 12.
ARM 2: Patients receive lutetium Lu 177 dotatate intravenously (IV) over 4 hours on day 1 of each cycle. Treatment repeats every 56 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Six to twelve weeks later, patients undergo SOC cytoreductive surgery. Patients also undergo MRI or CT during screening, 7-14 days prior to surgery, at weeks 44 and 56, then every 12 weeks until PD. Patients also undergo gallium Ga 68-DOTATATE PET/CT during screening and at week 44.
After completion of study treatment, patients are followed every 12 weeks until PD.
Lead OrganizationUniversity of Chicago Comprehensive Cancer Center
Principal InvestigatorXavier M. Keutgen
