Neoadjuvant PRRT With 177Lu-DOTATATE Followed by Surgery for Resectable PanNET

NCT04385992 | Completed Phase 2

• 1 other identifier: Neo.Lu.Pa.NET
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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:

1. 1.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
2. 2.Quality of life (QoL) after neoadjuvant PRRT followed by pancreatic surgical resection.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (2)

• Postoperative morbidity

  Rate of postoperative 90-day morbidity after neoadjuvant PRRT with 177Lu-DOTATATE followed by pancreatic resection

  from week 40 until week 52

• Postoperative mortality

  Rate of postoperative 90-day mortality after neoadjuvant PRRT with 177Lu-DOTATATE followed by pancreatic resection

  from week 40 until week 52

Secondary Outcomes (1)

• Radiological response

  week 38

Study Arms (1)

All enrolled patients

EXPERIMENTAL

Enrolled patients following inclusion criteria

Drug: 177Lu-Dotatate

Interventions

177Lu-Dotatate DRUG

Peptide Receptor Radionuclide Therapy (PRRT) is based on specific somatostatin receptor targeting with radiolabelled analogues 90Y-DOTATOC and 177Lu-DOTATATE

All enrolled patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ASA ≤ 3
• 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)

You may not qualify if:

• 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
• ASA \> 3
• 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

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

Ospedale San Raffaele

Milan, 20132, Italy

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Massimo Falconi, Professor

  Ospedale San Raffaele IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 9, 2020
• First Posted: May 13, 2020
• Study Start: March 9, 2020
• Primary Completion: January 25, 2023
• Study Completion: June 26, 2023
• Last Updated: June 27, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)