Personalized PRRT of Neuroendocrine Tumors (P-PRRT)

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

Tracking Information

• First Submitted Date: March 10, 2016
• First Posted Date: April 28, 2016
• Last Update Posted Date: July 17, 2020
• Actual Study Start Date: April 12, 2016
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: 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: Personalized PRRT of Neuroendocrine Tumors
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Neuroendocrine Tumors
• Carcinoid Tumor
• Carcinoma, Neuroendocrine

Intervention

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

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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 15, 2020): 300
• Original Estimated Enrollment (submitted: April 25, 2016): 85
• Estimated Study Completion Date: December 2026
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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: Canada

Administrative Information

• NCT Number: NCT02754297
• Other Study ID Numbers: A14-11-2181
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: CHU de Quebec-Universite Laval
• Original Responsible Party: Same as current
• Current Study Sponsor: CHU de Quebec-Universite Laval
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: CHU de Quebec-Universite Laval
• Verification Date: July 2020