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Personalized PRRT of Neuroendocrine Tumors (P-PRRT)

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ClinicalTrials.gov Identifier: NCT02754297
Recruitment Status : Recruiting
First Posted : April 28, 2016
Last Update Posted : July 17, 2020
Sponsor:
Information provided by (Responsible Party):
CHU de Quebec-Universite Laval

Tracking Information
First Submitted Date  ICMJE March 10, 2016
First Posted Date  ICMJE April 28, 2016
Last Update Posted Date July 17, 2020
Actual Study Start Date  ICMJE April 12, 2016
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 25, 2016)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2016)
  • 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.
  • Overall survival (OS) [ Time Frame: 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.
  • 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.
  • 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.
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 25, 2016)
  • 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
  • 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)
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Personalized PRRT of Neuroendocrine Tumors
Official Title  ICMJE Personalized Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Phase 2 Study
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroendocrine Tumors
  • Carcinoid Tumor
  • Carcinoma, Neuroendocrine
Intervention  ICMJE 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:
  • LuTate
  • 177Lu-[DOTA0,Tyr3]octreotate
  • 177Lu-DOTATATE
Study Arms  ICMJE 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).
Intervention: Drug: 177Lu-Octreotate
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 15, 2020)
300
Original Estimated Enrollment  ICMJE
 (submitted: April 25, 2016)
85
Estimated Study Completion Date  ICMJE December 2026
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jean-Mathieu Beauregard, MD,MSc,FRCPC 418-525-4444 medecine.nucleaire@mail.chudequebec.ca
Contact: Geneviève Filion 418-525-4444 medecine.nucleaire@mail.chudequebec.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02754297
Other Study ID Numbers  ICMJE A14-11-2181
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party CHU de Quebec-Universite Laval
Original Responsible Party Same as current
Current Study Sponsor  ICMJE CHU de Quebec-Universite Laval
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jean-Mathieu Beauregard, MD,MSc,FRCPC CHU de Québec - Université Laval
PRS Account CHU de Quebec-Universite Laval
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP