Methodology of the SORENTO clinical trial: a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET.

BACKGROUND: The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG). METHODS: SORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator's choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events. DISCUSSION: This is the first trial investigating the efficacy of CAM2029 versus SoC SRL therapy using a head-to-head, superiority trial design. It is expected to be the first trial to investigate the efficacy of increased dosing frequency of a high-exposure SRL. A BIRC will limit bias and measurement variability and ensure high-quality efficacy data. Additionally, inclusion of patients with well-differentiated Grade 3 NET may elucidate treatment strategies for this rarely investigated patient population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05050942. Registered on 21st September 2021.

Patient-Reported Outcomes of Treatment of Opioid Dependence With Weekly and Monthly Subcutaneous Depot vs Daily Sublingual Buprenorphine: A Randomized Clinical Trial.

Importance: Patient-reported outcomes in the treatment of opioid dependence may differ between subcutaneously administered depot buprenorphine and daily sublingual buprenorphine. Objective: To compare patient satisfaction between depot buprenorphine and sublingual buprenorphine in adult outpatients with opioid dependence. Design, Setting, and Participants: This open-label, randomized clinical trial was conducted among adult patients with opioid dependence at 6 outpatient clinical sites in Australia from October 2018 to September 2019. Data analysis was conducted from October 2019 to May 2020. Interventions: Participants were randomized to receive treatment with weekly or monthly depot buprenorphine or daily sublingual buprenorphine over 24 weeks. Main Outcomes and Measures: The primary end point was the difference in global treatment satisfaction, assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4 (range, 0-100; higher score indicates greater satisfaction) at week 24. Secondary end points included other patient-reported outcomes, including quality of life, treatment burden, and health-related outcomes, as well as measures of opioid use, retention in treatment, and safety. Results: A total of 119 participants (70 [58.8%] men; mean [SD] age, 44.4 [10.5] years) were enrolled, randomized to, and received either depot buprenorphine (60 participants [50.4%]) or sublingual buprenorphine (59 participants [49.6%]). From the initial sample of 120, a participant (0.8%) in the sublingual buprenorphine group withdrew consent and did not receive study treatment. All participants were receiving sublingual buprenorphine when enrolled. The mean TSQM global satisfaction score was significantly higher for the depot group compared with the sublingual group at week 24 (mean [SE] score, 82.5 [2.3] vs 74.3 [2.3]; difference, 8.2; 95% CI, 1.7 to 14.6; P = .01). Improved outcomes were also observed for several secondary end points after treatment with depot buprenorphine (eg, mean [SE] treatment burden assessed by the Treatment Burden Questionnaire global score, on which lower scores indicate lower burden: 13.2 [2.6] vs 28.6 [2.5]; difference, -15.4; 95% CI, -22.6 to -8.2; P < .001). Thirty-nine participants (65.0%) in the depot buprenorphine group experienced 117 adverse drug reactions, mainly injection site reactions of mild intensity following subcutaneous administration, and 12 participants (20.3%) in the sublingual buprenorphine group experienced 21 adverse drug reactions. No participants withdrew from the trial medication or the trial due to adverse events. Conclusions and Relevance: In this study, participants receiving depot buprenorphine reported improved treatment satisfaction compared with those receiving sublingual buprenorphine. The results highlight the application of patient-reported outcomes as alternative end points to traditional markers of substance use in addiction treatment outcome studies. Trial Registration: anzctr.org.au Identifier: ANZCTR12618001759280.