Personalized PRRT of Neuroendocrine Tumors (P-PRRT)

May 31, 2023 updated by: CHU de Quebec-Universite Laval

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Quebec
      • Quebec City, Quebec, Canada, G1R 2J6
        • Recruiting
        • CHU de Québec - Université Laval
        • Contact:
        • Sub-Investigator:
          • François-Alexandre Buteau, MD, FRCPC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Personalized PRRT (P-PRRT)

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
  • 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.
Other Names:
  • 177Lu-DOTATATE
  • LuTate
  • 177Lu-[DOTA0,Tyr3]octreotate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 3 months after induction course
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)
Time Frame: Time from first cycle to date of disease progression or death, reported up to 5 years after accrual closure
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 Frame: Time from first cycle to date of death, reported up to 5 years after accrual closure
Time from first cycle to date of death, reported up to 5 years after accrual closure
Symptomatic response rate
Time Frame: 3 months after induction course
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
Time Frame: 3 months after induction course
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
Time Frame: 3 months after induction course
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
Time Frame: From the first treatment cycle administration until 5 years after accrual closure or death, whichever came first
From the first treatment cycle administration until 5 years after accrual closure or death, whichever came first

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor radiation dose-response relationship
Time Frame: 3 months after induction course
Correlation between cumulative absorbed radiation dose to tumor lesions and 3-month objective response rate, as defined above
3 months after induction course
Tumor radiation dose-survival relationship
Time Frame: At least 5 years after first cycle or until study completion, whichever came first
Correlation between cumulative absorbed radiation dose to tumor lesions and survival endpoints above (PFS and OS)
At least 5 years after first cycle or until study completion, whichever came first
Renal radiation dose-chronic toxicity relationship
Time Frame: At least 5 years after first cycle or until study completion, whichever came first
Correlation between cumulative absorbed radiation dose to kidney and variations in glomerular filtration rate from baseline, reported annually for at least 5 years after first cycle or until study completion.
At least 5 years after first cycle or until study completion, whichever came first
Bone marrow radiation dose-chronic toxicity relationship
Time Frame: At least 5 years after first cycle or until study completion, whichever came first
Correlation between cumulative absorbed radiation dose to bone marrow and chronic variations of blood counts from baseline, reported annually for at least 5 years after first cycle or until study completion.
At least 5 years after first cycle or until study completion, whichever came first
Bone marrow radiation dose-subacute toxicity relationship
Time Frame: Time of nadir blood counts values between 2 and 6 weeks after each cycle
Correlation between per-cycle absorbed radiation dose to bone marrow and subacute variations (nadir values between 2 and 6 weeks) of blood counts from baseline, for each cycle.
Time of nadir blood counts values between 2 and 6 weeks after each cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CHU de Quebec-Universite Laval

Investigators

  • Principal Investigator: Jean-Mathieu Beauregard, MD,MSc,FRCPC, CHU de Québec - Université Laval

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 12, 2016

Primary Completion (Estimated)

April 12, 2025

Study Completion (Estimated)

April 12, 2029

Study Registration Dates

First Submitted

March 10, 2016

First Submitted That Met QC Criteria

April 25, 2016

First Posted (Estimated)

April 28, 2016

Study Record Updates

Last Update Posted (Actual)

June 1, 2023

Last Update Submitted That Met QC Criteria

May 31, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A14-11-2181

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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