Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET

Brief summary public domain (ClinicalTrials.gov)

This study will estimate the treatment effect of everolimus in combination with pasireotide LAR relative to everolimus alone on progression-free survival (PFS) in patients with advanced progressive PNET. A planned primary analysis was completed with data cut of 02-Apr-2014. The study did not meet its primary objective, which was based on progression-free survival (PFS) as per local radiology assessment and was prematurely terminated with the last patient last visit on 19-Feb-2015. However, it is important to note that the data did not reveal any new safety concerns. It was decided to stop the study and this decision was shared with the study sites on 31-Jul-2014.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Progression-free Survival (PFS) Per Local Radiological Review [Once 80 PFS events had occurred aproximately after 24 months]. Median, months (95% Confidence Interval). Paseriotide LAR + Everolimus (n=79): 16.82 (12.09 to 19.58); Everolimus (n=81): 16.59 (11.07 to 19.48). Analysis, Paseriotide LAR + Everolimus vs Everolimus: Hazard Ratio (HR) 0.991 (95% CI 0.636 to 1.543); p=0.488; Log Rank; superiority or other.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR [Once 80 PFS events had occurred]. Number, Participants. Deaths: Paseriotide LAR + Everolimus (n=78): 7; Everolimus (n=81): 10. Serious Adverse Events: Paseriotide LAR + Everolimus (n=78): 41; Everolimus (n=81): 49. Adverse Events: Paseriotide LAR + Everolimus (n=78): 78; Everolimus (n=81): 81.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR) as Per Radiology Review [Once 80 PFS events had occurred]. Number, Percentage of participants (95% Confidence Interval). Paseriotide LAR + Everolimus (n=79): 20.3 (12.0 to 30.8); Everolimus (n=81): 6.2 (2.0 to 13.8).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Duration of Response (DoR) [Once 80 PFS events had occurred].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) Using Kaplan Meier Method [Once 80 PFS events had occurred]. Number, Percentage of participants (95% Confidence Interval). 6 months: Paseriotide LAR + Everolimus (n=79): 93.5 (85.0 to 97.2); Everolimus (n=81): 93.7 (85.5 to 97.3). 12 months: Paseriotide LAR + Everolimus (n=79): 85.5 (75.4 to 91.7); Everolimus (n=81): 86.1 (76.2 to 92.0). 18 months: Paseriotide LAR + Everolimus (n=79): 81.4 (70.6 to 88.5); Everolimus (n=81): 75.5 (64.3 to 83.6). 24 months: Paseriotide LAR + Everolimus (n=79): 77.0 (65.6 to 85.1); Everolimus (n=81): 71.0 (59.3 to 79.9).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PFS and the Predictive Probability of Success in Phase III [Once 105 PFS events had occurred occurred].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease Control Rate (DCR) as Per Radiology Review [Once 80 PFS events had occurred]. Number, Percentage of participants (95% Confidence Interval). Paseriotide LAR + Everolimus (n=79): 77.2 (66.4 to 85.9); Everolimus (n=81): 82.7 (72.7 to 90.2).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Summary of Pharmacokinetics (PK) for Everolimus for AUClast [Cycle 2 Day 1]. Mean, ng*hr/mL (Standard Deviation). Paseriotide LAR + Everolimus (n=5): 511 (91.8); Everolimus (n=8): 378 (123).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Summary of Pharmacokinetics (PK) for Everolimus for CL/F [Cycle 2 Day 1]. Mean, L/hr (Standard Deviation). Paseriotide LAR + Everolimus (n=5): 20.0 (3.21); Everolimus (n=8): 29.0 (9.51).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin [Cycle 2 Day 1]. Mean, ng/mL (Standard Deviation). Cmax: Paseriotide LAR + Everolimus (n=6): 58.7 (25.9); Everolimus (n=9): 60.2 (30.6). Cmin: Paseriotide LAR + Everolimus (n=6): 14.7 (4.81); Everolimus (n=9): 7.67 (4.41).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Summary of Pharmacokinetics (PK) for Everolimus for Tmax [Cycle 2 Day 1]. Median, hr (Inter-Quartile Range). Paseriotide LAR + Everolimus (n=6): 1.00 (0.333 to 5.00); Everolimus (n=9): 0.500 (0.500 to 5.00).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg [Cycle 1 Day 21, Cycle 2 Day 29]. Mean, ng/mL (Standard Deviation). Cycle 1 Day 21 (n:69): Paseriotide LAR + Everolimus (n=69): 21.6 (0.333 to 5.00). Cycle 2 Day 29 (n: 64): Paseriotide LAR + Everolimus (n=69): 19.9 (12.1).