Trial Outcomes & Findings for Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET (NCT NCT01374451)

Last Updated: 2016-12-20

Results Overview

PFS per RECIST 1.0. (Response Evaluation Criteria in Solid Tumors). PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

160 participants

Primary outcome timeframe

Once 80 PFS events had occurred aproximately after 24 months

Results posted on

2016-12-20

Participant Flow

Participant milestones

Participant milestones
Measure	Paseriotide LAR + Everolimus everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im	Everolimus everolimus 10 mg once daily po alone
Overall Study STARTED	79	81
Overall Study COMPLETED	78	81
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Paseriotide LAR + Everolimus everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im	Everolimus everolimus 10 mg once daily po alone
Overall Study Administrative problems	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paseriotide LAR + Everolimus n=79 Participants everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im	Everolimus n=81 Participants everolimus 10 mg once daily po alone	Total n=160 Participants Total of all reporting groups
Age, Continuous	56.52 Years STANDARD_DEVIATION 11.978 • n=5 Participants	58.22 Years STANDARD_DEVIATION 12.650 • n=7 Participants	57.38 Years STANDARD_DEVIATION 12.314 • n=5 Participants
Gender Female	40 Participants n=5 Participants	34 Participants n=7 Participants	74 Participants n=5 Participants
Gender Male	39 Participants n=5 Participants	47 Participants n=7 Participants	86 Participants n=5 Participants

PRIMARY outcome

Timeframe: Once 80 PFS events had occurred aproximately after 24 months

Population: The FAS consisted of all randomized patients. Following the intention to treat principle patients were analyzed according to the treatment (and stratum) they were assigned to at randomization. One patient in the everolimus + pasireotide LAR treatment arm was untreated due to administrative problems.

Outcome measures

Outcome measures
Measure	Paseriotide LAR + Everolimus n=79 Participants everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im	Everolimus n=81 Participants everolimus 10 mg once daily po alone
Progression-free Survival (PFS) Per Local Radiological Review	16.82 months Interval 12.09 to 19.58	16.59 months Interval 11.07 to 19.48

SECONDARY outcome

Timeframe: Once 80 PFS events had occurred

Population: Safety analysis population included all patients who received any study medication (i.e. at least 1 dose of the study drug in case of monotherapy or at least 1 dose of any 1 compound of the study treatment in case of a combination therapy) with a post-Baseline safety assessment. See Adverse Events (AE) section for all AEs collected.

Consisted of monitoring and recording the rate, type, severity, and causal relationship of adverse events (AEs) and serious AEs (SAEs) to treatment. The safety analysis was based mainly on the frequency of AEs or SAEs and on the number of laboratory values that fell outside of pre-determined range.

Outcome measures

Outcome measures
Measure	Paseriotide LAR + Everolimus n=78 Participants everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im	Everolimus n=81 Participants everolimus 10 mg once daily po alone
Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR Deaths	7 Participants	10 Participants
Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR Serious Adverse Events	41 Participants	49 Participants
Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR Adverse Events	78 Participants	81 Participants

SECONDARY outcome

Timeframe: Once 80 PFS events had occurred

Population: The FAS consisted of all randomized patients.1 patient in the everolimus + pasireotide LAR treatment arm was untreated due to administrative problems. The study was terminated because the study did not meet its primary objective so minimal efficacy data was obtained.

Objective response was determined by the local radiologist according to the RECIST Version 1.0. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). This is also referred to as Overall response rate. CR: Disappearance of all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameter of all target lesions recorded at or after baseline.

Outcome measures

Outcome measures
Measure	Paseriotide LAR + Everolimus n=79 Participants everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im	Everolimus n=81 Participants everolimus 10 mg once daily po alone
Objective Response Rate (ORR) as Per Radiology Review	20.3 Percentage of participants Interval 12.0 to 30.8	6.2 Percentage of participants Interval 2.0 to 13.8

SECONDARY outcome

Timeframe: Once 80 PFS events had occurred

Population: The FAS consisted of all randomized patients. Only a low number of objective responses per RECIST was expected. Therefore, protocol was amended to only list duration of response, and confirmed responses were flagged in the listing. Hence, statistical analyses were not planned and such data are not available for the following table.

80 PFS are expected after approximately 24 months. Kaplan Meier was initially planned to be used to depict duration of response by treatment group and by stratum. Later based on the mode of action of everolimus and pasireotide and based on study experience, only a low number of objective responses per RECIST were expected. Therefore, protocol was amended to only list duration of response, and confirmed responses were flagged in the listing. Hence, statistical analyses were not planned and such data are not available for the following table.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Once 80 PFS events had occurred

Overall survival was defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival was to be censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Paseriotide LAR + Everolimus n=79 Participants everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im	Everolimus n=81 Participants everolimus 10 mg once daily po alone
Overall Survival (OS) Using Kaplan Meier Method 6 months	93.5 Percentage of participants Interval 85.0 to 97.2	93.7 Percentage of participants Interval 85.5 to 97.3
Overall Survival (OS) Using Kaplan Meier Method 12 months	85.5 Percentage of participants Interval 75.4 to 91.7	86.1 Percentage of participants Interval 76.2 to 92.0
Overall Survival (OS) Using Kaplan Meier Method 18 months	81.4 Percentage of participants Interval 70.6 to 88.5	75.5 Percentage of participants Interval 64.3 to 83.6
Overall Survival (OS) Using Kaplan Meier Method 24 months	77.0 Percentage of participants Interval 65.6 to 85.1	71.0 Percentage of participants Interval 59.3 to 79.9

SECONDARY outcome

Timeframe: Once 105 PFS events had occurred occurred

Population: Since the study was terminated because the study did not meet its primary objective which was based on PFS as per local radiology assessment, minimal efficacy data was obtained. Only 80 PFS events occurred before study was terminated so 105 PFS events was not reached to analyze this data.

105 PFS events expected after approximately 36 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Once 80 PFS events had occurred

Disease control rate is the percentage of patients with a best overall response of CR or PR or stable disease (SD) determined by the local radiologist according to the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) Version 1.0. CR: Disappearance of all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameter of all target lesions recorded at or after baseline. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD). PD: Any progression ≤ 18 weeks after randomization (and not qualifying for CR, PR or stable disease SD.