Clinical trial NCT02754297: Personalized PRRT of Neuroendocrine Tumors
Official title: Personalized Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Phase 2 Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Carcinoid Tumor
Carcinoma, Neuroendocrine
Keywords: Neuroendocrine tumors
Personalized
Peptide receptor radionuclide therapy
PRRT
177Lu-DOTATATE
177Lu-octreotate
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
First posted: 2016-04-28
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, peptide receptor radionuclide therapy (PRRT) with 177Lu-Octreotate (LuTate) will be personalized, i.e. administered activity of LuTate will be tailored for each patient to maximize absorbed radiation dose to tumor, while limiting that to healthy organs.

The purpose of this study is to:

* Assess the objective (radiological), symptomatic and biochemical response rates following an induction course of personalized PRRT;
* Assess the overall, the disease-specific, and the progression-free survival following P-PRRT;
* Correlate therapeutic response and survival with tumor absorbed radiation dose;
* Evaluate the acute, subacute and chronic adverse events following P-PRRT;
* Correlate toxicity (i.e. occurence and severity of adverse events) with absorbed radiation doses to organs at risk;
* Optimize the quantitative SPECT imaging-based dosimetry methods in a subset of 20 patients (sub-study funded by the Canadian Institutes of Health Research).

This study also has a compassionate purpose, which is to provide access to PRRT to patients.

Detailed description: A prospective, single-center, non-comparative, open phase 2 study. In this study, personalized peptide receptor radionuclide therapy (P-PRRT) with 177Lu-Octreotate (LuTate) will be administered to patients with progressive and/or symptomatic inoperable neuroendocrine tumors (NET) of any origin expressing the somatostatin receptor.

The primary objective to assess the objective response rate at 3 months following a four-cycle induction course of P-PRRT will be assessed for at least the first 85 participants.

This study as a compassionate aim to provide access to personalized PRRT patients at CHU de Québec - Université Laval center, and therefore this study has no pre-determined recruitment period duration or limited number of participants, and may remain open as long as necessary to fulfill this aim.

The study will continue until all participants have completed a minimum follow-up of 5 years. Interim analyses will be conducted annually.

Eligibility criteria: Inclusion Criteria:

* Patient suffering from a progressive and/or symptomatic NET (any site);
* Patient ineligible to, or refusing a potentially curative treatment such as surgical resection;
* Patient who did not respond, is intolerant or refuses other indicated and available palliative treatments;
* Demonstration of overexpression of somatostatin receptor by tumor lesions by scintigraphic imaging (Octreoscan or 68Ga positron emission tomography.

Exclusion Criteria:

* Pregnancy;
* Breastfeeding;.
* Very limited survival prognosis (i.e. less than a few weeks, because of the NET disease or any other condition) or Eastern Cooperative Oncology Group (ECOG) 4 performance status;
* Inability to obtain informed consent of the participant.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 3 months after induction course
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Time from first cycle to date of disease progression or death, reported up to 5 years after accrual closure
measure: Overall survival (OS)
timeFrame: Time from first cycle to date of death, reported up to 5 years after accrual closure
measure: Symptomatic response rate
timeFrame: 3 months after induction course
measure: Quality of life response
timeFrame: 3 months after induction course
measure: Biochemical response
timeFrame: 3 months after induction course
measure: Safety determined by type, frequency and severity of adverse events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03
timeFrame: From the first treatment cycle administration until 5 years after accrual closure or death, whichever came first
Other outcomes:
measure: Tumor radiation dose-response relationship
timeFrame: 3 months after induction course
measure: Tumor radiation dose-survival relationship
timeFrame: At least 5 years after first cycle or until study completion, whichever came first
measure: Renal radiation dose-chronic toxicity relationship
timeFrame: At least 5 years after first cycle or until study completion, whichever came first
measure: Bone marrow radiation dose-chronic toxicity relationship
timeFrame: At least 5 years after first cycle or until study completion, whichever came first
measure: Bone marrow radiation dose-subacute toxicity relationship
timeFrame: Time of nadir blood counts values between 2 and 6 weeks after each cycle
Locations:
city: Quebec City
country: Canada
facility: CHU de Québec - Université Laval
state: Quebec
Study officials:
affiliation: CHU de Québec - Université Laval
name: Jean-Mathieu Beauregard, MD,MSc,FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Del Prete M, Buteau FA, Arsenault F, Saighi N, Bouchard LO, Beaulieu A, Beauregard JM. Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial. Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):728-742. doi: 10.1007/s00259-018-4209-7. Epub 2018 Nov 30.