A Trial to Assess the Safety and Effectiveness of Lutetium-177 Octreotate Therapy in Neuroendocrine Tumours

Titre officiel

An Open-label Phase II Study of Lutetium-177 [DOTA0, Tyr3] Octreotate (Lu-DOTA-TATE) Treatment in Patients With Somatostatin Receptor Positive Tumours

Sommaire:

Les tumeurs neuroendocrines (TNE) sont rares, se développent lentement et le diagnostic est souvent retardé à cause des métastases avancées lors de la présentation. Le traitement aux radioisotopes s'est révélé être une thérapie palliative sûre et efficace chez les patients sélectionnés. Le Lutétium-177 (Lu-DOTA-TATE) a été utilisé au Cross Cancer Institute pour traiter 91 patients atteints des TNE depuis août 2010. Cette étude est menée parce que les experts cliniques administrent actuellement le traitement Lu-DOTA-TATE dans le cadre du Programme d'accès spécial (PAS) de Santé Canada (SC), chaque traitement individuel nécessitant une approbation distincte. SC a demandé que les experts cliniques expérimentent Lu-DOTA-TATE, dans le but d'obtenir l'autorisation de l'utiliser comme un agent de traitement commercialisé. Il y aura deux groupes de sujets : le Groupe A (traitement primaire) sera constitué de sujets atteints des tumeurs à récepteur positif de la somatostatine; le Groupe B (traitement secondaire) sera composé de sujets à qui le Lu-DOTA-TATE a déjà été administré dans le cadre du PAS. Tous le sujets seront traités dans une phase thérapeutique à l'aide d'une posologique de 8-12 semaines pendant 4 cycles suivis d'une phase d'entretien utilisant une posologie à intervalles de 22 à 26 semaines allant jusqu'à 8 cycles, avec un suivi de 22 à 26 semaines après l'administration de la dernière dose. L'innocuité sera évaluée par les signes vitaux, les examens hématologiques, l'activité fonctionnelle rénale et la collecte des déclarations d'événements indésirables.

Description de l'essai

Primary Outcome:

• Change in Tumour response of the target lesion(s) through end of treatment
• Median progression-free survival
• Lu-177 scan disease evaluation
• Change in tumour marker levels

Secondary Outcome:

• Number of participants with adverse events as a measure of safety and tolerability
• Change in haematology
• Change in renal function
• Change in liver function
• Median, 1, 2, 3, and 5-year overall survival
• Change in Quality of Life (EORTC QLQ)
• Change in Quality of Life (ESAS-r)
• Change in tumour biology (optional)

The proposed clinical trial will be a Phase II, open label, single site study in subjects with somatostatin receptor positive tumours. Radioactive Lu-DOTA-TATE doses are fixed within a range of 1.85 - 5.55 GBq ± 10%, with individual doses based on specified risk factors. There will be two groups of subjects enrolled in this study. Group A subjects (primary therapy) will have progressive somatostatin receptor positive tumours and have never received Lu-DOTA-TATE. Group B subjects (maintenance therapy) will be those subjects who have previously received Lu-DOTA-TATE under the Special Access Programme (SAP) and will maintain their treatment schedule when they are entered into the study.

All subjects in Group A will be treated in an induction stage using 10-14 week dosing for up to 4 treatments. If an individual patient shows stable or improving disease status with no significant toxicities after the 4 induction treatments, they will be assessed 12-20 weeks after the last therapeutic treatment for entry into the maintenance stage. Patients will be re-assessed for stable or improving disease status with no significant toxicities 12-20 weeks after every other treatment of the maintenance stage for consideration of further maintenance treatments (re-evaluations), up to a maximum of 8 treatments per patient if there have been no significant toxicities or progression. At each treatment, an amino acid solution is infused prior to and during the Lu-DOTA-TATE infusion to protect the kidneys. Subjects will be followed for 6 months and 1 year (± 4 weeks) following their last treatment dose to determine progression-free survival, and for 2, 3, and 5 years (± 4 weeks) following their last treatment dose to determine overall survival. All subjects meeting evaluation criteria will be analysed for safety, and all Group A subjects who have received at least two treatments of Lu-DOTA-TATE will be evaluated for efficacy. Those Group B subjects with adequate baseline data for comparison collected retrospectively from a chart review study (REV-LUT-001) may also be evaluated for safety and efficacy. Additional optional characterization of tumour samples from subjects who have had surgery before or during the study may be performed to characterize NET tumour biology changes following Lu-DOTA-TATE treatment.

Voir cet essai sur ClinicalTrials.gov