Personalized PRRT of Neuroendocrine Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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Personalized Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Phase 2 Study

Conditions
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Neuroendocrine Tumors, Carcinoid Tumor, Carcinoma, Neuroendocrine

Intervention / Treatment
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* Drug: 177Lu-Octreotate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Personalized PRRT (P-PRRT)<br>177Lu-Octreotate (LuTate) P-PRRT will be administered as follows: Renal absorbed radiation dose will be prescribed for the 4-cycle induction course (23 Gy) and for each subsequent cycle (6 Gy), with a reduction in cases of impaired renal or bone marrow function, or significant toxicity from prior cycles. The personalized activity to be administered at each cycle will be derived from renal dose per unit of injected activity that is predicted by patient characteristics or renal dose delivered during prior cycle(s). Participants responding to the induction course of P-PRRT will be eligible to receive additional consolidation and/or maintenance cycles. Participants with prior PRRT exposure outside the trial may receive less induction cycles, or only consolidation/maintenance cycle(s). | Drug: 177Lu-Octreotate<br>* The induction course will consist in 4 cycles at 8-10 weeks intervals. Concomitant amino acids will be administered for renal protection. Intra-arterial LuTate administration will be allowed in suitable cases. Dosimetry will be based on quantitative SPECT/CT imaging. In patients with hormonal symptoms, somatostatine analogues can be given between P-PRRT cycles.<br>* Other names: 177Lu-DOTATATE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Primary efficacy endpoint is the objective response rate on contrast-enhanced CT (or MRI) by RECIST criteria (and secondarily by South Western Oncology Group (SWOG) criteria) at 3 months after the 4th induction cycle of P-PRRT, in comparison to pre-treatment scan (within 3 months before commencing P-PRRT). | 3 months after induction course | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression of disease is defined as the time from first cycle to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria. | Time from first cycle to date of disease progression or death, reported up to 5 years after accrual closure | 
| Overall survival (OS) |  | Time from first cycle to date of death, reported up to 5 years after accrual closure | 
| Symptomatic response rate | Proportion of participants with improved, stable or worsened NET-related symptoms (frequency and severity), based on participant interviews at baseline and 3 months after completion of induction course. | 3 months after induction course | 
| Quality of life response | Proportion of participants with improved, stable or worsened quality of life score by EORTC quality of life questionnaires QLQ-C30 and QLQ-GI.NET21, administered at baseline and 3 months after induction course. | 3 months after induction course | 
| Biochemical response | Proportion of participants with improved (decreased by 25% or more), stable or worsened (increased by 25% or more) Chromogranin-A serum levels performed at baseline and 3 months after induction course. | 3 months after induction course | 
| 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 |  | From the first treatment cycle administration until 5 years after accrual closure or death, whichever came first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroendocrine tumors, Personalized, Peptide receptor radionuclide therapy, PRRT, 177Lu-DOTATATE, 177Lu-octreotate