Clinical Trial Results:
A Prospective Phase II Single-Arm Trial on Neoadjuvant Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE Followed by Surgery for resectable Pancreatic Neuroendocrine Tumors (Neo.Lu.Pa.NET)
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Summary
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EudraCT number |
2019-002196-34 |
Trial protocol |
IT |
Global end of trial date |
31 Aug 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jun 2026
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First version publication date |
06 Jun 2026
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Other versions |
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Summary report(s) |
Neolupanet scientific article |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
Neo.Lu.Pa.NET
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04385992 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
IRCCS Ospedale San Raffaele
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Sponsor organisation address |
Via Olgettina 60, Milano, Italy, 20132
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Public contact |
Pancreatic surgery Unit, IRCCS Ospedale San Raffaele, partelli.stefano@hsr.it
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Scientific contact |
Pancreatic surgery Unit, IRCCS Ospedale San Raffaele, partelli.stefano@hsr.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Jun 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Aug 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main aim of this study is to evaluate the safety of neoadjuvant PRRT with 177Lu-DOTATATE followed by surgical resection for resectable non-functioning PanNETs at high risk of recurrence.
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Protection of trial subjects |
During the administration of the therapy, performed into a dedicated room of the Nuclear Medicine Division, the Health Physics staff will monitor the patient by means of an ionization chamber, in order to check the completeness of the radiopeptide administration.
In order to obtain an adequate hydration of the patient and to protect the renal parenchyma during the phase of excretion of the radiopharmaceutical from an excessive tubular reuptake of radiopetide, the administration of the radiopharmaceutical will be preceded and followed (without interruption) with intravenous infusion of 1000 ml of 0.9% sodium chloride solution containing L-Arginine hydrochloride and/or Lysine.
Patients will also be recommended to perform frequent urination (especially during the first 6 hours following the infusion of the radiopharmaceutical) to reduce the dose absorbed in the bladder and gonads.
All prophylactic and therapeutic measures will be taken to prevent and control any complications due to massive disposal of biologically active substances during or immediately after treatment, such as the administration of steroids and/or antihistamines.
Patients will be hospitalized for at least 24 hours after the administration of 177Lu-DOTATATE and their discharge will be carried out in compliance with the constraints and radiation dose limits for family members and the population, according with the current Italian regulations (D.L 26 maggio 2000, n. 187). Moreover, each patient enrolled for PRRT will be given oral and written information about the rules of behaviour to be followed during the hospitalization and in the days following the discharge.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Mar 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 31
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Worldwide total number of subjects |
31
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EEA total number of subjects |
31
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
23
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
31 patients were recruited in Italy (Milan, Bologna, Pisa, Peschiera del Garda, Verona) between 2020 and 2021. | ||||||||||||||
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Pre-assignment
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Screening details |
All the patients should have performed at initial diagnosis the following procedures: o Thorax/abdomen CT scan with and without contrast enhancement o 68Gallium PET/CT or PET/MRI o Endoscopic ultra-sound with fine-needle aspiration/biopsy To be enrol in the study, all the patients should have a cytological/histological confirmation of PanNET. | ||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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177Lu-DOTATATE | ||||||||||||||
Arm description |
Enrolled patients will be treated with standard pancreatic resection according to PanNET localization, after a course (4 cycles) of neoadjuvant PRRT with 177Lu-DOTATATE. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
177Lu-DOTATATE
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection, Injection
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Routes of administration |
Injection , Intravenous use
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Dosage and administration details |
Patients will receive a cumulative activity of 29.600 MBq (800 mCi), divided in 4 administrations (or cycles) of 7.400 MBq (200 mCi) each, with treatment intervals of 6-8 weeks. The per-cycle activity of 177Lu-DOTATATE (and consequently the cumulative activity) might be reduced if relevant blood and renal toxicity, or other side effects, will occur during the course of PRRT.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
177Lu-DOTATATE
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Reporting group description |
Enrolled patients will be treated with standard pancreatic resection according to PanNET localization, after a course (4 cycles) of neoadjuvant PRRT with 177Lu-DOTATATE. | ||
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End point title |
Rate of postoperative 90-day morbidity and mortality [1] | ||||||||
End point description |
Rate of postoperative 90-day morbidity and mortality after neoadjuvant PRRT with 177Lu-DOTATATE followed by pancreatic resection.
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End point type |
Primary
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End point timeframe |
From week 40 until week 52.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a single arm trial, and to report a statistical analysis related to a specific endpoint it is required to define at least two comparison groups. Given that the statistical analysis for an endpoint is not mandatory, I decided to not insert it, otherwise it gives me Error. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Rate of objective radiological response to PRRT | ||||||||
End point description |
Rate of objective radiological response to PRRT with 177Lu-DOTATATE according to modified RECIST criteria (mRECIST).
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End point type |
Secondary
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End point timeframe |
Week 38.
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End point title |
Quality of life (QoL) | ||||||||
End point description |
The quality of life (QoL) at diagnostic workup, after neoadjuvant PRRT and after the pancreatic surgical resection, will be evaluated by EORTC-QLQ-C30 questionnaire.
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End point type |
Secondary
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End point timeframe |
Week 0, Week 38, Week 52.
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Adverse events information
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Timeframe for reporting adverse events |
The Investigator is responsible for reporting all Serious Adverse Events (SAE), related or not to the study treatment, occurring during the treatment period and within 90 days of the last protocol treatment, to the “Safety Desk”.
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Adverse event reporting additional description |
Any late Serious Adverse Drug Reaction (SADR), occurring after the 90-day period, should follow this reporting procedure:
Fill in the SAE form and send by fax within 24 hours of the initial observation of the event, to the sponsor.
Attach a report of the event and a copy of all examinations that were carried out, including laboratory tests.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Treated group
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Reporting group description |
All patients enrolled in this study have been treated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
