3-arm Trial to Evaluate Pasireotide LAR/Everolimus Alone/in Combination in Patients With Lung/Thymus NET - LUNA Trial (LUNA)

• ClinicalTrials.gov Identifier: NCT01563354
• Recruitment Status: Completed
• First Posted: March 27, 2012
• Results First Posted: April 2, 2021
• Last Update Posted: April 2, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neuroendocrine Carcinoma of the Lung and Thymus
• Interventions: Drug: Pasireotide LAR; Drug: Everolimus; Drug: Pasireotide LAR and Everolimus Combination
• Enrollment: 124

Participant Flow

Recruitment Details
Pre-assignment Details	Two patients completed the core phase of the study but they did not enter the extension phase one due to worsening in clinical conditions and one for Physician decision.

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Period Title: Core Phase
Started	41	42	41
Entered Extension Phase	12	14	15
Completed	12	14	15
Not Completed	29	28	26
Reason Not Completed
Adverse Event	5	15	13
Withdrawal by Subject	1	0	3
Lost to Follow-up	1	0	0
Death	1	5	2
Diseasse progression	18	7	8
Protocol deviation	2	0	0
PI decision - did not enter extension	0	1	0
Worsening of clinical condition - did not enter extension	1	0	0
Period Title: Extension Phase
Started	12 [1]	14 [1]	15
Completed	0	0	0
Not Completed	12	14	15
Reason Not Completed
Adverse Event	0	3	2
Withdrawal by Subject	0	1	0
Administration problems	3	2	3
Disease progression	9	8	10
[1] Criteria to enter Extension: continued clinical benefit and no unacceptable toxicity

Baseline Characteristics

Arm/Group Title		Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination	Total
Arm/Group Description		Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1	Total of all reporting groups
Overall Number of Baseline Participants		41	42	41	124
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	41 participants	42 participants	41 participants	124 participants
18 to <65		21	18	24	63
≥65 to 84		20	24	17	61
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	41 participants	42 participants	41 participants	124 participants
	Female	15 36.6%	19 45.2%	13 31.7%	47 37.9%
	Male	26 63.4%	23 54.8%	28 68.3%	77 62.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	41 participants	42 participants	41 participants	124 participants
Caucasian		40 97.6%	42 100.0%	40 97.6%	122 98.4%
Black		1 2.4%	0 0.0%	0 0.0%	1 0.8%
Asian		0 0.0%	0 0.0%	1 2.4%	1 0.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Progression-free at 9 Months Based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
Description	Patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at Month 9 were to be considered as "progression-free" based on RECIST v1.1. Patients with missing tumor assessment, or with overall lesion response "unknown" at Month 9 were considered as "non progression-free", unless any of the following assessments at Week 48 or Week 52 indicate CR, PR, or SD, in which case the patient was to be considered as progression-free at Month 9. Patients discontinuing the study for any reason prior to the 9 month assessment were to be considered as "non progression-free".
Time Frame	Baseline up to 9 months

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	41	42	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Complete response	0; (0.0 to 8.6)	0; (0.0 to 8.4)	0; (0.0 to 8.6)
Partial response	2.4; (0.1 to 12.9)	2.4; (0.1 to 12.6)	2.4; (0.1 to 12.9)
Stable disease	34.1; (20.1 to 50.6)	31.0; (17.6 to 47.1)	48.8; (32.9 to 64.9)
Progression-free (PF) at Month 9	39.0; (24.2 to 55.5)	33.3; (19.6 to 49.5)	58.5; (42.1 to 73.7)

2. Secondary Outcome

Title	Summary of Progression-free Survival (PFS) Based on RECIST v1.1
Description	Time from first study drug administration to objective tumor progression or death from any cause according to RECIST v1.1
Time Frame	Baseline, every 3 months up to 69 months

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	41	42	41
Median (95% Confidence Interval); Unit of Measure: months
	8.51; (5.68 to 14.03)	12.48; (5.55 to 20.21)	16.53; (11.10 to 23.26)

3. Secondary Outcome

Title	Kaplan-Meier Estimates of Progression-free Survival (PFS)
Description	Percent (%) event-free probability estimate is the estimated probability that a patient will remain event-free up to the specified time point. Percent event-free probability estimates are obtained from the Kaplan-Meier survival estimates. Events are time from first study drug administration to objective tumor progression or death from any cause according to RECIST v1.1.
Time Frame	Baseline, every 3 months up to 69 months

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	41	42	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: event free probability estimates
3 months	83.6; (67.1 to 92.3)	91.2; (75.1 to 97.1)	88.6; (72.4 to 95.5)
6 months	68.2; (49.8 to 81.1)	63.5; (44.7 to 77.4)	85.5; (68.6 to 93.7)
9 months	49.6; (31.9 to 65.1)	56.9; (38.1 to 71.9)	79.2; (61.1 to 89.5)
12 months	39.9; (23.3 to 56.0)	50.2; (31.9 to 66.0)	55.5; (36.4 to 71.0)
15 months	32.6; (17.2 to 49.1)	46.8; (28.9 to 62.9)	51.2; (32.1 to 67.5)
18 months	21.8; (9.1 to 37.8)	38.6; (21.4 to 55.6)	42.7; (24.2 to 60.1)
21 months	14.5; (4.7 to 29.6)	29.4; (13.6 to 47.2)	38.0; (20.0 to 55.9)
24 months	14.5; (4.7 to 29.6)	19.6; (6.7 to 37.4)	28.5; (12.5 to 46.9)
27 months	14.5; (4.7 to 29.6)	19.6; (6.7 to 37.4)	28.5; (12.5 to 46.9)
30 months	10.9; (2.8 to 25.2)	9.8; (1.8 to 26.2)	19.0; (6.3 to 36.9)
33 months	10.9; (2.8 to 25.2)	9.8; (1.8 to 26.2)	19.0; (6.3 to 36.9)
36 months	10.9; (2.8 to 25.2)	9.8; (1.8 to 26.2)	14.2; (3.7 to 31.5)
39 months	10.9; (2.8 to 25.2)	9.8; (1.8 to 26.2)	14.2; (3.7 to 31.5)
42 months	10.9; (2.8 to 25.2)	9.8; (1.8 to 26.2)	14.2; (3.7 to 31.5)
45 months	10.9; (2.8 to 25.2)	9.8; (1.8 to 26.2)	14.2; (3.7 to 31.5)
48 months	10.9; (2.8 to 25.2)	9.8; (1.8 to 26.2)	14.2; (3.7 to 31.5)
51 months	10.9; (2.8 to 25.2)	NA [1]; (NA to NA)	14.2; (3.7 to 31.5)
54 months	10.9; (2.8 to 25.2)	NA [1]; (NA to NA)	14.2; (3.7 to 31.5)
57 months	10.9; (2.8 to 25.2)	NA [1]; (NA to NA)	7.1; (0.6 to 25.2)
60 months	10.9; (2.8 to 25.2)	NA [1]; (NA to NA)	7.1; (0.6 to 25.2)
63 months	10.9; (2.8 to 25.2)	NA [1]; (NA to NA)	7.1; (0.6 to 25.2)
66 months	NA [1]; (NA to NA)	NA [1]; (NA to NA)	7.1; (0.6 to 25.2)
69 months	NA [1]; (NA to NA)	NA [1]; (NA to NA)	7.1; (0.6 to 25.2)

[1]

Event-free probability is non-estimable due to insufficient number of participants with events

4. Secondary Outcome

Title	Summary of Time to Response (Months)
Description	Time from start of treatment to the first observed objective tumor response (partial response or complete response) observed according to RECIST v1.1.
Time Frame	Every 3 months up to Year 1

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:		Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed		41	42	41
Measure Type: Number; Unit of Measure: months
25th percentile	Number Analyzed	1 participants	1 participants	2 participants
		NA [1]	NA [1]	NA [1]
Median	Number Analyzed	1 participants	1 participants	2 participants
		NA [1]	NA [1]	NA [1]
75th percentile	Number Analyzed	1 participants	1 participants	2 participants
		NA [1]	NA [1]	NA [1]

[1]

Percentile is not available due to due to insufficient number

5. Secondary Outcome

Title	Summary of Duration of Response (Months)
Description	Date of first objective tumor response to date of tumor progression or death due to any cause.
Time Frame	Every 3 months up to Year 1

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:		Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed		41	42	41
Measure Type: Number; Unit of Measure: months
25th percentile	Number Analyzed	1 participants	1 participants	2 participants
		NA [1]	NA [1]	NA [1]
Median	Number Analyzed	1 participants	1 participants	2 participants
		NA [1]	NA [1]	NA [1]
75th percentile	Number Analyzed	1 participants	1 participants	2 participants
		NA [1]	NA [1]	NA [1]

[1]

Percentile is not available due to due to insufficient number

6. Secondary Outcome

Title	12-month Disease Control Rate (DCR) and Objective Response Rate (ORR)
Description	Objective response rate (ORR) was defined as the percentage of patients showing a best overall response (BOR) of CR or PR during the core study according to RECIST v1.1 criteria. The best overall response is interpreted as the best response recorded from the start of the treatment until disease progression/recurrence, death from any cause or until the patient withdraws consent, whichever is earliest. DCR was was defined as the percentage of participants with a best overall response of complete response, partial response or stable disease during 12 months of treatment according to RECIST v1.1.
Time Frame	Baseline up to Month 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	41	42	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Objective response (CR+PR)	2.4; (0.1 to 12.9)	2.4; (0.1 to 12.6)	4.9; (0.6 to 16.5)
Disease control rate (CR+PR+SD)	80.5; (65.1 to 91.2)	73.8; (58.0 to 86.1)	78.0; (62.4 to 89.4)
Complete response (CR)	0; (0.0 to 8.6)	0; (0.0 to 8.4)	0; (0.0 to 8.6)
Partial response (PR)	2.4; (0.1 to 12.9)	2.4; (0.1 to 12.6)	4.9; (0.6 to 16.5)
Stable disease	78.0; (62.4 to 89.4)	71.4; (55.4 to 84.3)	73.2; (57.1 to 85.8)
Progressive disease	14.6 [1]; (NA to NA)	4.8 [1]; (NA to NA)	7.3 [1]; (NA to NA)
Unknown	2.4 [1]; (NA to NA)	4.8 [1]; (NA to NA)	0 [1]; (NA to NA)
Not assessed	2.4 [1]; (NA to NA)	16.7 [1]; (NA to NA)	14.6 [1]; (NA to NA)
Discontinued before month 12	68.3 [1]; (NA to NA)	64.3 [1]; (NA to NA)	63.4 [1]; (NA to NA)

[1]

Event-free probability is non-estimable due to insufficient number of participants with events

7. Secondary Outcome

Title	Biochemical Response Rate (BRR) for Chromogranin A (CgA) Levels
Description	Percentage of patients showing normalization or a decrease of ≥ 30% of serum CgA concentrations compared to baseline.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set participants with CgA levels outside normal range at baseline.

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	34	27	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Week 12	20.6; (8.7 to 37.9)	7.4; (0.9 to 24.3)	17.1; (6.6 to 33.6)
Week 24	8.8; (1.9 to 23.7)	7.4; (0.9 to 24.3)	20.0; (8.4 to 36.9)
Week 36	8.8; (1.9 to 23.7)	3.7; (0.1 to 19.0)	11.4; (3.2 to 26.7)
Week 48	8.8; (1.9 to 23.7)	0; (0.0 to 12.8)	11.4; (3.2 to 26.7)
Week 52	5.9; (0.7 to 19.7)	0; (0.0 to 12.8)	5.7; (0.7 to 19.2)

8. Secondary Outcome

Title	Duration of Biochemical Response (DBR), by Treatment (Full Analysis Set)
Description	Time from the first documentation of biochemical response to the first documentation of biochemical progression or to death due to any cause, whichever occurred first. Biochemical progression is defined as an increase of serum CgA levels ≥ 25% compared to baseline.
Time Frame	Baseline up to Month 18

Outcome Measure Data

Analysis Population Description

Full analysis set - participants who have experienced biochemical response during the study and had CgA levels outside normal range at baseline

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	8	4	9
Median (95% Confidence Interval); Unit of Measure: months
	14.75 [1]; (0.03 to NA)	2.00 [1]; (0.03 to NA)	8.38 [1]; (0.03 to NA)

[1]

Upper-bound of CI is non-estimable due to insufficient number of events

9. Secondary Outcome

Title	Kaplan-Meier Event-free Probability Estimate Based on CgA Levels
Description	Kaplan Meier estimates are for Duration of biochemical response (DBR) outcome measure. Events are biochemical progressions i.e. an increase of CgA levels >= 25% compared to baseline or deaths due to any cause. Percent (%) Event-free probability estimate is the estimated probability that a patient will remain event-free up to the specified time point.
Time Frame	Baseline, every 3 months up to Month 18

Outcome Measure Data

Analysis Population Description

Full analysis set - participants who have experienced biochemical response during the study and had CgA levels outside normal range at baseline

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	8	4	9
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: event free probability estimates
3 months	75.0; (31.5 to 93.1)	37.5; (1.1 to 80.8)	77.8; (36.5 to 93.9)
6 months	56.3; (14.7 to 84.2)	NA [1]; (NA to NA)	77.8; (36.5 to 93.9)
9 months	56.3; (14.7 to 84.2)	NA [1]; (NA to NA)	44.4; (13.6 to 71.9)
12 months	56.3; (14.7 to 84.2)	NA [1]; (NA to NA)	44.4; (13.6 to 71.9)
15 months	37.5; (5.6 to 71.7)	NA [1]; (NA to NA)	44.4; (13.6 to 71.9)
18 months	37.5; (5.6 to 71.7)	NA [1]; (NA to NA)	44.4; (13.6 to 71.9)

[1]

Event-free probability is non-estimable due to insufficient number of participants with events

10. Secondary Outcome

Title	Summary of Biochemical Progression-free Survival Based on CgA Levels by Treatment
Description	Time from the first documentation of biochemical response to the first documentation of biochemical progression or to death due to any cause, whichever occurred first. Biochemical progression is defined as an increase of serum CgA levels ≥ 25% compared to baseline.
Time Frame	Baseline up Month 24

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	41	42	41
Median (95% Confidence Interval); Unit of Measure: months
	2.89; (2.79 to 5.49)	2.86; (2.79 to 3.52)	5.62; (3.9 to 8.31)

11. Secondary Outcome

Title	Kaplan-Meier Event-free Probability Estimate for Biochemical Progression-free Survival Based on CgA Levels
Description	Percent (%) Event-free probability estimate is the estimated probability that a patient will remain event-free up to the specified time point. Percent event-free probability estimates are obtained from the Kaplan-Meier survival estimates. Events are biochemical progressions, i.e., an increase of CgA levels >= 25% compared to baseline or deaths due to any cause.
Time Frame	Baseline, every 3 months up to Month 24

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	41	42	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: event free probability estimates
3 months	43.1; (26.4 to 58.6)	35.4; (20.0 to 51.1)	77.1; (59.4 to 87.8)
6 months	29.5; (15.0 to 45.6)	17.7; (7.2 to 32.0)	44.5; (27.6 to 60.0)
9 months	18.5; (7.1 to 34.0)	11.0; (3.2 to 24.5)	29.7; (15.5 to 45.2)
12 months	18.5; (7.1 to 34.0)	7.4; (1.4 to 20.0)	26.4; (13.0 to 41.9)
15 months	18.5; (7.1 to 34.0)	NA [1]; (NA to NA)	18.1; (6.7 to 33.8)
18 months	13.8; (4.1 to 29.4)	NA [1]; (NA to NA)	18.1; (6.7 to 33.8)
21 months	13.8; (4.1 to 29.4)	NA [1]; (NA to NA)	18.1; (6.7 to 33.8)
24 months	NA [1]; (NA to NA)	NA [1]; (NA to NA)	18.1; (6.7 to 33.8)

[1]

Event-free probability is non-estimable due to insufficient number of participants with events

12. Secondary Outcome

Title	Biochemical Response Rate (BRR) for 5HIAA Levels
Description	The percentages are the biochemical response rates i.e. percentage of patients showing normalization i.e. return to within normal ranges, or a decrease of >= 50% from baseline of 5HIAA concentrations.
Time Frame	Baseline up Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set - participants with 5HIAA levels within normal range at baseline are excluded from the table, therefore 'n' stands for the number of patients with 5-HIAA levels outside normal range at baseline.

Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description:	Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1	Everolimus 10 mg taken orally (p.o) once daily starting on Day 1	Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
Overall Number of Participants Analyzed	20	18	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Week 12	20.0; (5.7 to 43.7)	11.1; (1.4 to 34.7)	10.0; (1.2 to 31.7)
Week 24	5.0; (0.1 to 24.9)	11.1; (1.4 to 34.7)	20.0; (5.7 to 43.7)
Week 36	5.0; (0.1 to 24.9)	11.1; (1.4 to 34.7)	5.0; (0.1 to 24.9)
Week 48	5.0; (0.1 to 24.9)	0; (0.0 to 18.5)	5.0; (0.1 to 24.9)
Week 52	5.0; (0.1 to 24.9)	0; (0.0 to 18.5)	10.0; (1.2 to 31.7)

Adverse Events

Time Frame	Adverse events were reported from first dose of study treatment until end of study treatment plus 8 weeks post treatment up to maximum duration of 316 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
Arm/Group Description	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
All-Cause Mortality
	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/41 (4.88%)	7/42 (16.67%)	3/41 (7.32%)
Serious Adverse Events
	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	17/41 (41.46%)	20/42 (47.62%)	16/41 (39.02%)
Blood and lymphatic system disorders
Anaemia † 1	0/41 (0.00%)	1/42 (2.38%)	1/41 (2.44%)
Cardiac disorders
Atrial flutter † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Cardiac failure † 1	1/41 (2.44%)	1/42 (2.38%)	0/41 (0.00%)
Tachycardia paroxysmal † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Endocrine disorders
Carcinoid crisis † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Carcinoid syndrome † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Cushing's syndrome † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	0/41 (0.00%)	2/42 (4.76%)	0/41 (0.00%)
Abdominal pain upper † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Ascites † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Constipation † 1	2/41 (4.88%)	0/42 (0.00%)	0/41 (0.00%)
Diarrhoea † 1	1/41 (2.44%)	3/42 (7.14%)	2/41 (4.88%)
Dysphagia † 1	0/41 (0.00%)	2/42 (4.76%)	0/41 (0.00%)
Ileus † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Intestinal obstruction † 1	1/41 (2.44%)	0/42 (0.00%)	1/41 (2.44%)
Nausea † 1	0/41 (0.00%)	2/42 (4.76%)	0/41 (0.00%)
Salivary gland pain † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Stomatitis † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Vomiting † 1	1/41 (2.44%)	1/42 (2.38%)	1/41 (2.44%)
General disorders
Asthenia † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Axillary pain † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Chest pain † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Disease progression † 1	1/41 (2.44%)	1/42 (2.38%)	0/41 (0.00%)
Face oedema † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
General physical health deterioration † 1	3/41 (7.32%)	2/42 (4.76%)	0/41 (0.00%)
Multiple organ dysfunction syndrome † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Non-cardiac chest pain † 1	1/41 (2.44%)	1/42 (2.38%)	0/41 (0.00%)
Oedema peripheral † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Pyrexia † 1	1/41 (2.44%)	3/42 (7.14%)	1/41 (2.44%)
Hepatobiliary disorders
Cholecystocholangitis † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Hepatic failure † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Jaundice † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Infections and infestations
Aspergillus infection † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Febrile infection † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Gastroenteritis † 1	1/41 (2.44%)	1/42 (2.38%)	0/41 (0.00%)
Lower respiratory tract infection † 1	1/41 (2.44%)	1/42 (2.38%)	0/41 (0.00%)
Oesophageal candidiasis † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Pneumonia † 1	5/41 (12.20%)	2/42 (4.76%)	0/41 (0.00%)
Sepsis † 1	1/41 (2.44%)	1/42 (2.38%)	0/41 (0.00%)
Urinary tract infection † 1	2/41 (4.88%)	1/42 (2.38%)	0/41 (0.00%)
Urosepsis † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Injury, poisoning and procedural complications
Contusion † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Haematuria traumatic † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Radiation oesophagitis † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Investigations
Blood creatinine increased † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
C-reactive protein increased † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Liver function test increased † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Weight decreased † 1	0/41 (0.00%)	2/42 (4.76%)	0/41 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Diabetes mellitus † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Hyperammonaemia † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Hypercalcaemia † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Hyperglycaemia † 1	0/41 (0.00%)	1/42 (2.38%)	1/41 (2.44%)
Hyperkalaemia † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Hyponatraemia † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Metabolic acidosis † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Nervous system disorders
Altered state of consciousness † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Brain compression † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Headache † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Loss of consciousness † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Spinal cord compression † 1	2/41 (4.88%)	0/42 (0.00%)	0/41 (0.00%)
Syncope † 1	2/41 (4.88%)	0/42 (0.00%)	0/41 (0.00%)
Psychiatric disorders
Confusional state † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Delirium † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Depression † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Renal and urinary disorders
Acute kidney injury † 1	0/41 (0.00%)	2/42 (4.76%)	1/41 (2.44%)
Anuria † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Dysuria † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Bronchospasm † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Cough † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Dyspnoea † 1	3/41 (7.32%)	3/42 (7.14%)	1/41 (2.44%)
Hydrothorax † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Lung disorder † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Pleural effusion † 1	3/41 (7.32%)	1/42 (2.38%)	0/41 (0.00%)
Pneumonia aspiration † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Pneumonitis † 1	0/41 (0.00%)	2/42 (4.76%)	2/41 (4.88%)
Pulmonary embolism † 1	1/41 (2.44%)	2/42 (4.76%)	1/41 (2.44%)
Respiratory distress † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Respiratory failure † 1	0/41 (0.00%)	1/42 (2.38%)	1/41 (2.44%)
Skin and subcutaneous tissue disorders
Angioedema † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Rash † 1	0/41 (0.00%)	1/42 (2.38%)	0/41 (0.00%)
Skin haemorrhage † 1	1/41 (2.44%)	0/42 (0.00%)	0/41 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	0/41 (0.00%)	0/42 (0.00%)	1/41 (2.44%)
Hypotension † 1	2/41 (4.88%)	0/42 (0.00%)	0/41 (0.00%)
1 Term from vocabulary, MedDRA (22.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pasireotide LAR	Everolimus	Pasireotide LAR and Everolimus Combination
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	40/41 (97.56%)	42/42 (100.00%)	40/41 (97.56%)
Blood and lymphatic system disorders
Anaemia † 1	9/41 (21.95%)	14/42 (33.33%)	10/41 (24.39%)
Leukopenia † 1	0/41 (0.00%)	3/42 (7.14%)	3/41 (7.32%)
Thrombocytopenia † 1	0/41 (0.00%)	9/42 (21.43%)	7/41 (17.07%)
Cardiac disorders
Palpitations † 1	4/41 (9.76%)	1/42 (2.38%)	1/41 (2.44%)
Ear and labyrinth disorders
Vertigo † 1	3/41 (7.32%)	0/42 (0.00%)	0/41 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	15/41 (36.59%)	6/42 (14.29%)	6/41 (14.63%)
Abdominal pain upper † 1	5/41 (12.20%)	5/42 (11.90%)	3/41 (7.32%)
Aphthous ulcer † 1	0/41 (0.00%)	3/42 (7.14%)	0/41 (0.00%)
Constipation † 1	9/41 (21.95%)	6/42 (14.29%)	0/41 (0.00%)
Diarrhoea † 1	17/41 (41.46%)	21/42 (50.00%)	33/41 (80.49%)
Dyspepsia † 1	1/41 (2.44%)	0/42 (0.00%)	3/41 (7.32%)
Dysphagia † 1	0/41 (0.00%)	4/42 (9.52%)	0/41 (0.00%)
Flatulence † 1	2/41 (4.88%)	0/42 (0.00%)	4/41 (9.76%)
Haemorrhoids † 1	3/41 (7.32%)	1/42 (2.38%)	4/41 (9.76%)
Mouth ulceration † 1	0/41 (0.00%)	3/42 (7.14%)	6/41 (14.63%)
Nausea † 1	11/41 (26.83%)	10/42 (23.81%)	8/41 (19.51%)
Steatorrhoea † 1	4/41 (9.76%)	0/42 (0.00%)	2/41 (4.88%)
Stomatitis † 1	2/41 (4.88%)	26/42 (61.90%)	14/41 (34.15%)
Toothache † 1	2/41 (4.88%)	1/42 (2.38%)	4/41 (9.76%)
Vomiting † 1	5/41 (12.20%)	5/42 (11.90%)	4/41 (9.76%)
General disorders
Asthenia † 1	11/41 (26.83%)	12/42 (28.57%)	16/41 (39.02%)
Chills † 1	4/41 (9.76%)	0/42 (0.00%)	0/41 (0.00%)
Fatigue † 1	6/41 (14.63%)	9/42 (21.43%)	16/41 (39.02%)
Non-cardiac chest pain † 1	3/41 (7.32%)	4/42 (9.52%)	3/41 (7.32%)
Oedema peripheral † 1	8/41 (19.51%)	13/42 (30.95%)	12/41 (29.27%)
Pyrexia † 1	7/41 (17.07%)	7/42 (16.67%)	6/41 (14.63%)
Infections and infestations
Bronchitis † 1	2/41 (4.88%)	3/42 (7.14%)	1/41 (2.44%)
Cystitis † 1	1/41 (2.44%)	4/42 (9.52%)	0/41 (0.00%)
Folliculitis † 1	0/41 (0.00%)	1/42 (2.38%)	4/41 (9.76%)
Influenza † 1	5/41 (12.20%)	2/42 (4.76%)	2/41 (4.88%)
Lower respiratory tract infection † 1	0/41 (0.00%)	1/42 (2.38%)	4/41 (9.76%)
Rhinitis † 1	3/41 (7.32%)	1/42 (2.38%)	0/41 (0.00%)
Urinary tract infection † 1	4/41 (9.76%)	2/42 (4.76%)	7/41 (17.07%)
Investigations
Alanine aminotransferase increased † 1	3/41 (7.32%)	3/42 (7.14%)	3/41 (7.32%)
Aspartate aminotransferase increased † 1	4/41 (9.76%)	3/42 (7.14%)	1/41 (2.44%)
Blood alkaline phosphatase increased † 1	7/41 (17.07%)	2/42 (4.76%)	2/41 (4.88%)
Blood creatinine increased † 1	2/41 (4.88%)	1/42 (2.38%)	3/41 (7.32%)
Gamma-glutamyltransferase increased † 1	10/41 (24.39%)	4/42 (9.52%)	4/41 (9.76%)
Glycosylated haemoglobin increased † 1	3/41 (7.32%)	1/42 (2.38%)	3/41 (7.32%)
Platelet count decreased † 1	0/41 (0.00%)	1/42 (2.38%)	3/41 (7.32%)
Weight decreased † 1	18/41 (43.90%)	18/42 (42.86%)	24/41 (58.54%)
Metabolism and nutrition disorders
Decreased appetite † 1	10/41 (24.39%)	16/42 (38.10%)	13/41 (31.71%)
Diabetes mellitus † 1	9/41 (21.95%)	4/42 (9.52%)	8/41 (19.51%)
Hypercholesterolaemia † 1	1/41 (2.44%)	7/42 (16.67%)	5/41 (12.20%)
Hyperglycaemia † 1	18/41 (43.90%)	14/42 (33.33%)	36/41 (87.80%)
Hypertriglyceridaemia † 1	3/41 (7.32%)	9/42 (21.43%)	5/41 (12.20%)
Hypoglycaemia † 1	2/41 (4.88%)	2/42 (4.76%)	3/41 (7.32%)
Hypokalaemia † 1	2/41 (4.88%)	3/42 (7.14%)	5/41 (12.20%)
Hypomagnesaemia † 1	4/41 (9.76%)	2/42 (4.76%)	3/41 (7.32%)
Hyponatraemia † 1	2/41 (4.88%)	0/42 (0.00%)	3/41 (7.32%)
Hypophosphataemia † 1	1/41 (2.44%)	3/42 (7.14%)	5/41 (12.20%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	3/41 (7.32%)	1/42 (2.38%)	3/41 (7.32%)
Back pain † 1	10/41 (24.39%)	6/42 (14.29%)	7/41 (17.07%)
Bone pain † 1	2/41 (4.88%)	2/42 (4.76%)	3/41 (7.32%)
Joint swelling † 1	2/41 (4.88%)	1/42 (2.38%)	3/41 (7.32%)
Muscle spasms † 1	5/41 (12.20%)	2/42 (4.76%)	1/41 (2.44%)
Musculoskeletal chest pain † 1	4/41 (9.76%)	2/42 (4.76%)	2/41 (4.88%)
Musculoskeletal pain † 1	4/41 (9.76%)	1/42 (2.38%)	2/41 (4.88%)
Neck pain † 1	3/41 (7.32%)	1/42 (2.38%)	0/41 (0.00%)
Pain in extremity † 1	3/41 (7.32%)	1/42 (2.38%)	4/41 (9.76%)
Nervous system disorders
Dizziness † 1	6/41 (14.63%)	2/42 (4.76%)	2/41 (4.88%)
Dysgeusia † 1	4/41 (9.76%)	5/42 (11.90%)	4/41 (9.76%)
Headache † 1	7/41 (17.07%)	4/42 (9.52%)	6/41 (14.63%)
Presyncope † 1	3/41 (7.32%)	0/42 (0.00%)	0/41 (0.00%)
Taste disorder † 1	0/41 (0.00%)	0/42 (0.00%)	3/41 (7.32%)
Psychiatric disorders
Insomnia † 1	2/41 (4.88%)	4/42 (9.52%)	3/41 (7.32%)
Renal and urinary disorders
Dysuria † 1	3/41 (7.32%)	2/42 (4.76%)	1/41 (2.44%)
Polyuria † 1	1/41 (2.44%)	0/42 (0.00%)	3/41 (7.32%)
Renal failure † 1	2/41 (4.88%)	4/42 (9.52%)	0/41 (0.00%)
Urinary incontinence † 1	0/41 (0.00%)	0/42 (0.00%)	3/41 (7.32%)
Reproductive system and breast disorders
Erectile dysfunction † 1	0/41 (0.00%)	0/42 (0.00%)	3/41 (7.32%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	9/41 (21.95%)	12/42 (28.57%)	14/41 (34.15%)
Dyspnoea † 1	8/41 (19.51%)	11/42 (26.19%)	6/41 (14.63%)
Epistaxis † 1	0/41 (0.00%)	5/42 (11.90%)	3/41 (7.32%)
Haemoptysis † 1	0/41 (0.00%)	1/42 (2.38%)	3/41 (7.32%)
Pneumonitis † 1	0/41 (0.00%)	2/42 (4.76%)	4/41 (9.76%)
Productive cough † 1	0/41 (0.00%)	2/42 (4.76%)	7/41 (17.07%)
Skin and subcutaneous tissue disorders
Dry skin † 1	0/41 (0.00%)	3/42 (7.14%)	4/41 (9.76%)
Onychoclasis † 1	0/41 (0.00%)	3/42 (7.14%)	3/41 (7.32%)
Palmar-plantar erythrodysaesthesia syndrome † 1	0/41 (0.00%)	3/42 (7.14%)	2/41 (4.88%)
Pruritus † 1	2/41 (4.88%)	2/42 (4.76%)	7/41 (17.07%)
Rash † 1	3/41 (7.32%)	12/42 (28.57%)	6/41 (14.63%)
Vascular disorders
Flushing † 1	1/41 (2.44%)	2/42 (4.76%)	4/41 (9.76%)
Hypertension † 1	2/41 (4.88%)	2/42 (4.76%)	3/41 (7.32%)
Hypotension † 1	3/41 (7.32%)	2/42 (4.76%)	1/41 (2.44%)
1 Term from vocabulary, MedDRA (22.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: + 1 862 778 8300
• EMail: Novartis.email@Novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ferolla P, Brizzi MP, Meyer T, Mansoor W, Mazieres J, Do Cao C, Lena H, Berruti A, Damiano V, Buikhuisen W, Gronbaek H, Lombard-Bohas C, Grohe C, Minotti V, Tiseo M, De Castro J, Reed N, Gislimberti G, Singh N, Stankovic M, Oberg K, Baudin E. Efficacy and safety of long-acting pasireotide or everolimus alone or in combination in patients with advanced carcinoids of the lung and thymus (LUNA): an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2017 Dec;18(12):1652-1664. doi: 10.1016/S1470-2045(17)30681-2. Epub 2017 Oct 23.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT01563354
• Other Study ID Numbers: CSOM230DIC03; 2011-002872-17 ( EudraCT Number )
• First Submitted: March 20, 2012
• First Posted: March 27, 2012
• Results First Submitted: February 4, 2021
• Results First Posted: April 2, 2021
• Last Update Posted: April 2, 2021