NCT04029428

Peptide Receptor Radionuclide Therapy in the Treatment of Advanced, Non-resectable and/or Symptomatic Tumors With SSTR Overexpression

Clinical Study of the Use of Yttrium-90 (90Y) and/or Lutecium-177 (177Lu) DOTATATE (DOTA-0-Tyr3-Octreotate) in the Treatment of Disseminated and / or Symptomatic Tumors With Somatostatin Receptor Overexpression

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: University of Warmia and Mazury · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

This is a non-randomized phase II , open label, comparative study. Patients with advanced non-resectable and/or progressive gastro-entero-pancreatic Neuroendocrine Tumours - GEP-NET, (G1, G2 and G3), Broncho-pulmonary Carcinoids (BPCs Atypical-AC or Typical-TC), pheochromocytoma/paraganglioma (PPGLs) and neuroendocrine tumours of unknown primary (NET-CUP) with overexpression of somatostatin receptor (SSTR positive) will be enrolled in the study and will be treated using Peptide Receptor Radionuclide Therapy (PRRT) initially with Yttrium-90 (90Y) DOTATATE (DOTA-0-Tyr3-Octreotate), and then compare to Lutecium-177 (177Lu) DOTATATE or mix of both Yttrium-90 (90Y) and Lutecium-177 (177Lu) DOTATATE. Total maximum activity for Yttrium-90 up to 4x3,7GBq, for Lutecium-177 up to 4x5,55GBq (Lu-177) and for both (mix) 4x3,7GBq (90Y and 177Lu 50% each).

Detailed description

This is a non-randomized phase II, open-label, comparative study. Patients with advanced, unresectable and/or progressive Gastro-Entero-Pancreatic Neuroendocrine Tumors - GEP-NET, (histological grade G1, G2 and G3), Broncho-Pulmonary Carcinoids (BPCs), including typical carcinoid (AC) and typical carcinoid (TC), pheochromocytoma/paragangliomas (PPGLs) and neuroendocrine tumors (cancers) of unknown primary (NET-CUP). All with overexpression of somatostatin receptor (SSTR positive) based on somatostatin receptor imaging (scintigraphy or PET), will be enrolled in this study. Initially patients will be assigned to single arm of PRRT using yttrium-90 (90Y) DOTATATE (DOTA-0-Tyr3-Octreotate) and then patients will be non-randomly assigned to one of the two groups lutecium-177 (177Lu) DOTATATE or mix yttrium (90Y) DOTATATE and lutecium-177 (177Lu) DOTATATE (50% each). The dosages (total activity used in each group of treated patients will be as follows: 1. Total activity of 90Y DOTATATE 4x3,7GBq (14,8 GBq) for 4 cycles at 8 ± 2 weeks (400mCi) 2. Total activity of 177Lu DOTATATE 4x5,55GBq (22,2 GBq for 4 cycles at 8 ± 2 weeks (600 mCi) 3. Total activity of mix both 90Y DOTATATE and 177Lu DOTATATE (50 each) 4x3,7 GBq for 4 cycles at 8 ± 2 weeks (400mCi). The non-randomized, phase II study design, allows for proposed initial active treatment arm using standard dose of 90Y DOTATATE and experimental treatment arm which composed of two options of PRRT with lutecium-177 DOTATATE or mix 90Y and 177Lu DOTATATE. The experimental therapy arm will be consisting of randomly allocated patients. Subjects including in this study will be evaluated in the mixed patients' population, including GEP-NET, bronchopulmonary carcinoid (BPCs), paraganglioma/pheochromocytomas (PPGLs) and NET of unknown origin (NET-CUP). Estimates of the original goals of the study can be assessed for each scheme separately using a two-step design using an external standard for comparison (the investigator's previous published results include standard PRRT using 90Y DOTATATE in subjects with GEP-NET). Although the sample size in this study is not based on any specific statistical hypothesis to compare separate groups of patients those with PRRT using 90Y DOTATATE, next those with 177Lu DOTATATE and those who will receive mix 90Y and 177Lu DOTATATE. This study design allows an objective set of clinical efficacy results in terms of PRRT responses and safety in these three treatment regimens in the same patient population, even different groups of tumors, which may be useful when planning next generation of the clinical trial using PRRT.

Conditions

• Neuroendocrine Tumors

Interventions

Type	Name	Description
DRUG	90Y-DOTATATE	Total activity of 90Y DOTATATE, 4x3.7GBq (14.8 GBq). Single session of i.v. infusion of 90Y DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 90Y DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.
DRUG	(177Lu-DOTAOTyr3)Octreotate	Total activity of 177Lu DOTATATE, 4x5.55GBq (22.2 GBq). Single session of i.v. infusion of 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.
DRUG	90Y DOTATATE and 177Lu DOTATATE (mix each of 50%)	Total activity of 90Y DOTATATE and 177Lu DOTATATE, 4x3.7GBq (14.8 GBq 50% each 90Y and 177Lu). Single session of i.v. infusion of 90Y and 177Lu DOTATATE administered for 20 min via infusion pump with co-infusion of amino-acids solution 1000ml for 1h before and then et least 6h after 177Lu DOTATATE infusion. Therapy consists up to 4 cycles at 8 ± 2 weeks between each other.

Timeline

• Start date: 2004-11-02
• Primary completion: 2021-01-01
• Completion: 2021-01-01
• First posted: 2019-07-23
• Last updated: 2020-04-01

Locations

1 site across 1 country: Poland