A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours (NETTER-1)

• ClinicalTrials.gov Identifier: NCT01578239
• Recruitment Status: Completed
• First Posted: April 16, 2012
• Results First Posted: October 2, 2017
• Last Update Posted: April 4, 2022
• Sponsor: Advanced Accelerator Applications
• Information provided by (Responsible Party): Advanced Accelerator Applications

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Carcinoid Tumor of the Small Bowel; Neuroendocrine Tumour
• Interventions: Drug: Octreotide LAR; Drug: 177Lu-DOTA0-Tyr3-Octreotate
• Enrollment: 231

Participant Flow

Recruitment Details	The study was conducted in 41 sites across 8 countries.
Pre-assignment Details

Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Period Title: Treatment Period
Started [1]	117	114
Full Analysis Set (FAS) [2]	117	114
Safety Analysis Set (SAF) [3]	111	112
FAS-Entered Long-term Follow-up	101	99
Completed [4]	50	13
Not Completed	67	101
Reason Not Completed
Progressive Disease	19	64
Physician Decision	17	17
Adverse Event	13	10
Non-compliance	2	0
Withdrawal by Subject	10	9
Other	6	1
[1] All patients who received a randomization number, regardless of receiving study medication were included in the Randomized Set; [2] All randomized participant were analyzed according to randomized treatment, regardless of the actual treatment received.; [3] All randomized patients who received at least one dose of active study medication. In the SAF, patients were analyzed based on actual treatment received.; [4] refers to completion of a minimum of 72 weeks of treatment.
Period Title: Long-term Follow-Up Period
Started	101 [1]	99 [1]
Completed [2]	24	19
Not Completed	77	80
Reason Not Completed
Death	69	64
Consent withdrawal	4	10
Lost to Follow-up	2	4
Other	2	2
[1] FAS-Entered long-term follow-up; [2] Study ended 5 years from randomization of last participant or 158 deaths in the study achieved

Baseline Characteristics

Arm/Group Title		177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR	Total
Arm/Group Description		30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.	Total of all reporting groups
Overall Number of Baseline Participants		117	114	231
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	117 participants	114 participants	231 participants
		63.4 (9.34)	64.0 (9.80)	63.7 (9.55)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	117 participants	114 participants	231 participants
	Female	54 46.2%	60 52.6%	114 49.4%
	Male	63 53.8%	54 47.4%	117 50.6%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	117 participants	114 participants	231 participants
Asian		1	0	1
Black or African American		5	5	10
Hispanic		6	3	9
White		93	96	189
Other		0	1	1
Not Applicable		12	9	21

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Progression Free Survival (PFS) was defined as the time from randomization to documented centrally assessed disease progression, as evaluated by the Independent Review Committee (IRC), or death due to any cause. If a participant had no centrally assessed progression and had not died at the time of the primary endpoint analysis, the participant was regarded as censored in the context of a time to event analysis at the date of last evaluable tumor assessment. Disease progression was determined by objective tumor response status using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1).
Time Frame	From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached on 24July2015, assessed up to approximately 34 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed	117	114
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	8.5; (5.8 to 9.1)

[1]

NA: not estimable due to number of censored participants at the time the analysis cut off date was reached.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-DOTA0-Tyr3-Octreotate, Octreotide LAR
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Derived from a two-sided test between the two groups
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.177
	Confidence Interval	(2-Sided) 95%; 0.108 to 0.289
	Estimation Comments	Hazard ratio is expressed as Lu-DOTA-Tyr-Octreotate / Octreotide LAR and estimated from the corresponding Cox model.

2. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Objective Response Rate (ORR) was calculated as the proportion of patients with tumour size reduction (sum of partial responses (PR) and complete responses (CR)) according to RECIST 1.1.
Time Frame	From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached on 24July2015, assessed up to approximately 34 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS). Only participants with available post-baseline CT scans were considered.

Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed	102	100
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	14.7; (7.8 to 21.6)	4.0; (0.2 to 7.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-DOTA0-Tyr3-Octreotate, Octreotide LAR
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0141
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause or the date of last contact (censored observation) prior to the date of the data cut-off, and during the entire study period (i.e. the treatment period plus follow-up).
Time Frame	From date of randomization until date of death from any cause up to final safety cut-off date reached on 18Jan2021, assessed up to approximately 100 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed	117	114
Median (95% Confidence Interval); Unit of Measure: Months
	48.0; (37.4 to 55.2)	36.3; (25.9 to 51.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-DOTA0-Tyr3-Octreotate, Octreotide LAR
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3039
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.17
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Rate of Overall Survival (OS)
Description	Survival estimates were collected every 12 Months up to 60 Months to compare OS between the two treatment groups.
Time Frame	12 months, 24 months, 36 months, 48 months, 60 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed	117	114
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Survival Estimates
12 months	91.0; (84.0 to 95.1)	79.7; (70.8 to 86.1)
24 months	76.0; (66.7 to 83.0)	62.7; (52.6 to 71.2)
36 months	61.4; (51.4 to 69.9)	50.1; (40.0 to 59.4)
48 months	49.5; (39.5 to 58.6)	41.8; (31.8 to 51.4)
60 months	37.1; (27.8 to 46.4)	35.4; (25.7 to 45.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-DOTA0-Tyr3-Octreotate, Octreotide LAR
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3039
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.17
	Estimation Comments	Hazard Ratio of Lu-DOTA-Tyr-Octreotate vs. Octreotide LAR

5. Secondary Outcome

Title	Time to Tumour Progression (TTP)
Description	Time to Tumour Progression (TTP) was defined as the time from randomization to progression centrally assessed. It included patients who dropped out due to toxicity, but omitted patients who died without measured progression (censored to last follow-up date or death date).
Time Frame	From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached on 24July2015, assessed up to approximately 34 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS).

Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed	117	114
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	8.7; (6.0 to 11.1)

[1]

NA: not estimable due to number of censored participants at the time the analysis cut off date was reached.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-DOTA0-Tyr3-Octreotate, Octreotide LAR
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.137
	Confidence Interval	(2-Sided) 95%; 0.077 to 0.242
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Duration of Response (DoR)
Description	The Duration of Response (DoR) was defined as the time from initially meeting the criteria for response (CR or PR) until the time of progression by RECIST 1.1.
Time Frame	From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached on 24July2015, assessed up to approximately 34 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS). Only Participants with an Objective Response are included in the analysis.

Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed	15	4
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (2.8 to NA)	1.9 [1]; (1.9 to NA)

[1]

NA: not estimable due to number of censored participants at the time the analysis cut off date was reached.

7. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths, through the monitoring of relevant clinical and laboratory safety parameters.
Time Frame	From informed consent signature through study completion reached at final safety cutoff date on 18July2021, assessed up to approximately 101 Months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAF).

Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed	111	112
Measure Type: Count of Participants; Unit of Measure: Participants
Adverse Events (AEs)	105 94.6%	90 80.4%
Serious Adverse Events (SAEs)	40 36.0%	31 27.7%
Deaths during treatment period	4 3.6%	5 4.5%
Deaths during follow-up period	66 59.5%	63 56.3%

8. Secondary Outcome

Title	Change From Baseline in the EORTC QLQ-C30 Questionnaire
Description	The Quality of Life Questionnaire C30 (QLQ-C30) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess quality of life in cancer patients. It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from "not at all" to "very much" for most items. Raw scores are linearly transformed so each score ranged a 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement).
Time Frame	Inclusion (Baseline) (BL), Week 72, Week 120

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAF). Values at Inclusion were taken from last non-missing value prior to randomization (the only scheduled pre-randomization assessment was at the Baseline visit). Calculations at each visit included only participants with scores at the visit and Inclusion.

Arm/Group Title		177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:		30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed		111	112
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Physical functioning: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		3.232 (12.4857)	-4.242 (10.0101)
Physical functioning: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		-3.333 (4.7140)
Role functioning: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		5.051 (33.1989)	-3.030 (16.3608)
Role functioning: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		8.333 (11.7851)
Emotional functioning: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		7.744 (22.6602)	6.061 (17.9083)
Emotional functioning: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		12.500 (5.8926)
Cognitive functioning: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		5.556 (15.9571)	1.515 (13.8535)
Cognitive functioning: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		16.667 (23.5702)
Social functioning: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		8.586 (28.9039)	-7.576 (18.8025)
Social functioning: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		8.333 (35.3553)
Global Health Status/QoL: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		5.556 (21.4155)	1.515 (10.4205)
Global Health Status/QoL: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		-16.667 (0.0000)
Fatigue: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-7.239 (24.7084)	-2.020 (13.8939)
Fatigue: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		11.111 (0.0000)
Nausea & Vomiting: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-4.545 (15.1799)	-4.545 (7.7850)
Nausea & Vomiting: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		0.000 (0.0000)
Pain: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-8.586 (22.4850)	-3.030 (10.0504)
Pain: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		0.000 (23.5702)
Dyspnoea: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-3.030 (22.6134)	3.030 (27.7070)
Dyspnoea: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		0.000 (0.0000)
Insomnia: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		0.000 (26.3523)	6.061 (29.1288)
Insomnia: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		33.333 (47.1405)
Appetite loss: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-8.081 (20.4639)	9.091 (21.5557)
Appetite loss: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		0.000 (0.0000)
Constipation: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		0.000 (18.6339)	0.000 (14.9071)
Constipation: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		0.000 (0.0000)
Diarrhoea: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-12.121 (36.1499)	-3.030 (27.7070)
Diarrhoea: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		-16.667 (23.5702)
Financial difficulties: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-7.071 (33.0798)	6.061 (20.1008)
Financial difficulties: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		-16.667 (70.7107)

9. Secondary Outcome

Title	Change From Baseline in the EORTC Quality of Life Questionnaire - Neuroendocrine Carcinoid Module (EORTC QLQ-GINET21)
Description	The Quality of Life GI Neuroendocrine Tumor survey (QLQ GINET21) contains a total of 21 items: four single-item assessments relating to muscle and/or bone pain (MBP), body image (BI), information (INF) and sexual functioning (SX), together with 17 items organized into five proposed scales: endocrine symptoms (ED; three items), GI symptoms (GI; five items), treatment-related symptoms (TR; three items), social functioning (SF) and disease-related worries (DRW; three items). The response format of the questionnaire is a four-point Likert scale. Responses are linearly transformed to a 0-100 scale using EORTC guidelines, with higher scores reflecting more severe symptoms.
Time Frame	Inclusion (Baseline) (BL), Week 72, Week 120

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAF). Values at Inclusion were taken from last non-missing value prior to randomization (the only scheduled pre-randomization assessment was at the Baseline visit). Calculations at each visit included only participants with scores at the visit and Inclusion.

Arm/Group Title		177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description:		30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
Overall Number of Participants Analyzed		112	111
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Endocrine scale: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-8.754 (20.1762)	-11.111 (21.0819)
Endocrine scale: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		0.000 (0.0000)
G.I. scale: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-2.727 (15.3083)	2.424 (10.0101)
G.I. scale: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		-13.333 (0.0000)
Treatment scale: chg from BL @ wk 72 (n=21,5)	Number Analyzed	21 participants	5 participants
		-8.995 (14.9563)	0.000 (11.1111)
Treatment scale: chg from BL @ wk 120 (n=1,0)	Number Analyzed	1 participants	0 participants
		-16.667 [1] (NA)
Social function scale: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-7.576 (23.3985)	-7.576 (21.1217)
Social function scale: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		11.111 (0.0000)
Diseases rel. worries scale: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-6.061 (27.9289)	1.010 (33.7765)
Diseases rel. worries scale: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		33.333 (31.4270)
Muscle/Bone pain symptom: chg from BL @ wk 72 (n=33,10)	Number Analyzed	33 participants	10 participants
		-5.051 (33.4594)	-16.667 (36.0041)
Muscle/Bone pain symptom: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		-16.667 (23.5702)
Sexual function: chg from BL @ wk 72 (n=21,7)	Number Analyzed	21 participants	7 participants
		6.349 (40.3031)	14.286 (17.8174)
Sexual function: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		50.000 (70.7107)
Information/Communication: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-4.040 (26.0309)	-12.121 (30.8139)
Information/Communication: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		0.000 (0.0000)
Body image: chg from BL @ wk 72 (n=33,11)	Number Analyzed	33 participants	11 participants
		-4.040 (18.1766)	-3.030 (17.9787)
Body image: chg from BL @ wk 120 (n=2,0)	Number Analyzed	2 participants	0 participants
		16.667 (23.5702)

[1]

Only one participant analyzed

Adverse Events

Time Frame	From informed consent signature through study completion reached at final safety cutoff date on 18July2021, assessed up to approximately 101 Months.
Adverse Event Reporting Description	Any sign or symptom that occurs after written informed consent provided.
Arm/Group Title	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
Arm/Group Description	30 mg Octreotide LAR treatment for symptom control continued until the end of study, unless the participant progressed or died.; Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) 177Lu-DOTA0-Tyr3-Octreotate: Four administrations of 7.4 GBq (200 mCi).; Concomitant amino acids were given with each administration for kidney protection.; 177Lu-DOTA0-Tyr3-Octreotate was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.	60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.; In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
All-Cause Mortality
	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
	Affected / at Risk (%)	Affected / at Risk (%)
Total	70/111 (63.06%)	68/112 (60.71%)
Serious Adverse Events
	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
	Affected / at Risk (%)	Affected / at Risk (%)
Total	40/111 (36.04%)	31/112 (27.68%)
Blood and lymphatic system disorders
Anaemia † 1	0/111 (0.00%)	1/112 (0.89%)
Lymphopenia † 1	2/111 (1.80%)	0/112 (0.00%)
Myelodysplastic syndrome † 1	1/111 (0.90%)	0/112 (0.00%)
Neutropenia † 1	1/111 (0.90%)	0/112 (0.00%)
Refractory cytopenia with unilineage dysplasia † 1	1/111 (0.90%)	0/112 (0.00%)
Cardiac disorders
Acute myocardial infarction † 1	1/111 (0.90%)	0/112 (0.00%)
Angina pectoris † 1	1/111 (0.90%)	0/112 (0.00%)
Arteriospasm coronary † 1	0/111 (0.00%)	1/112 (0.89%)
Atrioventricular block second degree † 1	1/111 (0.90%)	0/112 (0.00%)
Cardiac arrest † 1	1/111 (0.90%)	0/112 (0.00%)
Cardiac failure congestive † 1	0/111 (0.00%)	1/112 (0.89%)
Silent myocardial infarction † 1	1/111 (0.90%)	0/112 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	3/111 (2.70%)	1/112 (0.89%)
Abdominal pain lower † 1	0/111 (0.00%)	2/112 (1.79%)
Anal haemorrhage † 1	0/111 (0.00%)	1/112 (0.89%)
Ascites † 1	1/111 (0.90%)	1/112 (0.89%)
Diarrhoea † 1	0/111 (0.00%)	1/112 (0.89%)
Duodenal obstruction † 1	0/111 (0.00%)	1/112 (0.89%)
Gastritis † 1	1/111 (0.90%)	0/112 (0.00%)
Gastrointestinal obstruction † 1	0/111 (0.00%)	1/112 (0.89%)
Haematochezia † 1	1/111 (0.90%)	0/112 (0.00%)
Ileus † 1	0/111 (0.00%)	1/112 (0.89%)
Impaired gastric emptying † 1	0/111 (0.00%)	1/112 (0.89%)
Intestinal obstruction † 1	1/111 (0.90%)	0/112 (0.00%)
Malignant bowel obstruction † 1	0/111 (0.00%)	1/112 (0.89%)
Nausea † 1	0/111 (0.00%)	1/112 (0.89%)
Oesophagitis † 1	0/111 (0.00%)	1/112 (0.89%)
Small intestinal obstruction † 1	1/111 (0.90%)	2/112 (1.79%)
Vomiting † 1	2/111 (1.80%)	2/112 (1.79%)
General disorders
Complication of device insertion † 1	1/111 (0.90%)	0/112 (0.00%)
Device occlusion † 1	1/111 (0.90%)	0/112 (0.00%)
General physical health deterioration † 1	2/111 (1.80%)	2/112 (1.79%)
Generalised oedema † 1	0/111 (0.00%)	1/112 (0.89%)
Injection site hypersensitivity † 1	1/111 (0.90%)	0/112 (0.00%)
Pyrexia † 1	1/111 (0.90%)	0/112 (0.00%)
Hepatobiliary disorders
Cholecystitis † 1	1/111 (0.90%)	0/112 (0.00%)
Cholecystitis acute † 1	0/111 (0.00%)	1/112 (0.89%)
Cholestasis † 1	1/111 (0.90%)	0/112 (0.00%)
Hepatic encephalopathy † 1	1/111 (0.90%)	0/112 (0.00%)
Hepatocellular injury † 1	1/111 (0.90%)	0/112 (0.00%)
Infections and infestations
Clostridium difficile infection † 1	1/111 (0.90%)	0/112 (0.00%)
Device related infection † 1	1/111 (0.90%)	0/112 (0.00%)
Diverticulitis † 1	1/111 (0.90%)	0/112 (0.00%)
Pneumocystis jirovecii pneumonia † 1	1/111 (0.90%)	0/112 (0.00%)
Respiratory tract infection † 1	1/111 (0.90%)	0/112 (0.00%)
Sepsis † 1	1/111 (0.90%)	0/112 (0.00%)
Injury, poisoning and procedural complications
Femur fracture † 1	2/111 (1.80%)	0/112 (0.00%)
Limb injury † 1	0/111 (0.00%)	1/112 (0.89%)
Limb traumatic amputation † 1	1/111 (0.90%)	0/112 (0.00%)
Procedural complication † 1	1/111 (0.90%)	0/112 (0.00%)
Investigations
Blood creatinine increased † 1	1/111 (0.90%)	0/112 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	1/111 (0.90%)	1/112 (0.89%)
Fluid retention † 1	1/111 (0.90%)	0/112 (0.00%)
Hyperuricaemia † 1	0/111 (0.00%)	1/112 (0.89%)
Hypokalaemia † 1	1/111 (0.90%)	0/112 (0.00%)
Musculoskeletal and connective tissue disorders
Muscular weakness † 1	0/111 (0.00%)	1/112 (0.89%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	1/111 (0.90%)	1/112 (0.89%)
Breast cancer † 1	1/111 (0.90%)	0/112 (0.00%)
Breast cancer stage I † 1	0/111 (0.00%)	1/112 (0.89%)
Carcinoid crisis † 1	0/111 (0.00%)	1/112 (0.89%)
Diffuse large B-cell lymphoma † 1	1/111 (0.90%)	0/112 (0.00%)
Malignant melanoma in situ † 1	1/111 (0.90%)	0/112 (0.00%)
Malignant neoplasm progression † 1	2/111 (1.80%)	5/112 (4.46%)
Neoplasm progression † 1	0/111 (0.00%)	1/112 (0.89%)
Non-small cell lung cancer † 1	0/111 (0.00%)	1/112 (0.89%)
Oesophageal adenocarcinoma † 1	2/111 (1.80%)	0/112 (0.00%)
Prostate cancer † 1	0/111 (0.00%)	1/112 (0.89%)
Refractory cytopenia with multilineage dysplasia † 1	1/111 (0.90%)	0/112 (0.00%)
Squamous cell carcinoma † 1	1/111 (0.90%)	0/112 (0.00%)
Squamous cell carcinoma of skin † 1	1/111 (0.90%)	0/112 (0.00%)
Tumour invasion † 1	1/111 (0.90%)	0/112 (0.00%)
Nervous system disorders
Haemorrhage intracranial † 1	0/111 (0.00%)	1/112 (0.89%)
Syncope † 1	0/111 (0.00%)	1/112 (0.89%)
Thrombotic cerebral infarction † 1	0/111 (0.00%)	1/112 (0.89%)
Transient global amnesia † 1	0/111 (0.00%)	1/112 (0.89%)
Psychiatric disorders
Anxiety † 1	1/111 (0.90%)	0/112 (0.00%)
Delirium † 1	1/111 (0.90%)	0/112 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	4/111 (3.60%)	1/112 (0.89%)
Acute prerenal failure † 1	1/111 (0.90%)	0/112 (0.00%)
Renal impairment † 1	0/111 (0.00%)	1/112 (0.89%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/111 (0.90%)	0/112 (0.00%)
Cough † 1	1/111 (0.90%)	0/112 (0.00%)
Pleural effusion † 1	0/111 (0.00%)	1/112 (0.89%)
Surgical and medical procedures
Coronary artery bypass † 1	1/111 (0.90%)	0/112 (0.00%)
Vascular disorders
Inferior vena cava syndrome † 1	1/111 (0.90%)	0/112 (0.00%)
Pulmonary embolism † 1	1/111 (0.90%)	0/112 (0.00%)
Shock † 1	1/111 (0.90%)	0/112 (0.00%)
Syncope † 1	1/111 (0.90%)	0/112 (0.00%)
1 Term from vocabulary, MedDRA (18.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	177Lu-DOTA0-Tyr3-Octreotate	Octreotide LAR
	Affected / at Risk (%)	Affected / at Risk (%)
Total	105/111 (94.59%)	90/112 (80.36%)
Blood and lymphatic system disorders
Anaemia † 1	18/111 (16.22%)	8/112 (7.14%)
Lymphopenia † 1	18/111 (16.22%)	0/112 (0.00%)
Thrombocytopenia † 1	16/111 (14.41%)	0/112 (0.00%)
Cardiac disorders
Palpitations † 1	6/111 (5.41%)	6/112 (5.36%)
Gastrointestinal disorders
Abdominal distension † 1	18/111 (16.22%)	14/112 (12.50%)
Abdominal pain † 1	28/111 (25.23%)	21/112 (18.75%)
Abdominal pain upper † 1	6/111 (5.41%)	2/112 (1.79%)
Constipation † 1	11/111 (9.91%)	6/112 (5.36%)
Diarrhoea † 1	32/111 (28.83%)	20/112 (17.86%)
Dyspepsia † 1	7/111 (6.31%)	7/112 (6.25%)
Flatulence † 1	7/111 (6.31%)	6/112 (5.36%)
Nausea † 1	74/111 (66.67%)	13/112 (11.61%)
Vomiting † 1	59/111 (53.15%)	9/112 (8.04%)
General disorders
Asthenia † 1	9/111 (8.11%)	8/112 (7.14%)
Fatigue † 1	43/111 (38.74%)	30/112 (26.79%)
Influenza like illness † 1	6/111 (5.41%)	4/112 (3.57%)
Oedema peripheral † 1	18/111 (16.22%)	10/112 (8.93%)
Pyrexia † 1	8/111 (7.21%)	3/112 (2.68%)
Infections and infestations
Urinary tract infection † 1	7/111 (6.31%)	7/112 (6.25%)
Investigations
Alanine aminotransferase increased † 1	7/111 (6.31%)	7/112 (6.25%)
Aspartate aminotransferase increased † 1	5/111 (4.50%)	8/112 (7.14%)
Blood alkaline phosphatase increased † 1	7/111 (6.31%)	8/112 (7.14%)
Blood bilirubin increased † 1	7/111 (6.31%)	3/112 (2.68%)
Blood creatinine increased † 1	7/111 (6.31%)	6/112 (5.36%)
Gamma-glutamyltransferase increased † 1	7/111 (6.31%)	9/112 (8.04%)
Lymphocyte count decreased † 1	12/111 (10.81%)	2/112 (1.79%)
Platelet count decreased † 1	13/111 (11.71%)	2/112 (1.79%)
Weight decreased † 1	9/111 (8.11%)	8/112 (7.14%)
White blood cell count decreased † 1	7/111 (6.31%)	1/112 (0.89%)
Metabolism and nutrition disorders
Decreased appetite † 1	24/111 (21.62%)	12/112 (10.71%)
Hyperglycaemia † 1	11/111 (9.91%)	10/112 (8.93%)
Hypokalaemia † 1	9/111 (8.11%)	10/112 (8.93%)
Hyponatraemia † 1	7/111 (6.31%)	4/112 (3.57%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	12/111 (10.81%)	11/112 (9.82%)
Back pain † 1	15/111 (13.51%)	11/112 (9.82%)
Muscle spasms † 1	7/111 (6.31%)	2/112 (1.79%)
Musculoskeletal pain † 1	5/111 (4.50%)	6/112 (5.36%)
Pain in extremity † 1	12/111 (10.81%)	6/112 (5.36%)
Nervous system disorders
Dizziness † 1	19/111 (17.12%)	10/112 (8.93%)
Dysgeusia † 1	9/111 (8.11%)	2/112 (1.79%)
Headache † 1	21/111 (18.92%)	6/112 (5.36%)
Syncope † 1	6/111 (5.41%)	2/112 (1.79%)
Psychiatric disorders
Anxiety † 1	13/111 (11.71%)	6/112 (5.36%)
Insomnia † 1	3/111 (2.70%)	8/112 (7.14%)
Renal and urinary disorders
Haematuria † 1	7/111 (6.31%)	3/112 (2.68%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	12/111 (10.81%)	8/112 (7.14%)
Dyspnoea † 1	12/111 (10.81%)	9/112 (8.04%)
Skin and subcutaneous tissue disorders
Alopecia † 1	13/111 (11.71%)	2/112 (1.79%)
Vascular disorders
Flushing † 1	16/111 (14.41%)	10/112 (8.93%)
Hypertension † 1	13/111 (11.71%)	8/112 (7.14%)
1 Term from vocabulary, MedDRA (18.0); † 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 (ie, data from all sites) in the clinical trial.

Results Point of Contact

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

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

Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP; NETTER-1 investigators. 177Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-1763. doi: 10.1016/S1470-2045(21)00572-6. Epub 2021 Nov 15. Erratum In: Lancet Oncol. 2022 Feb;23(2):e59.

Strosberg J, Kunz PL, Hendifar A, Yao J, Bushnell D, Kulke MH, Baum RP, Caplin M, Ruszniewski P, Delpassand E, Hobday T, Verslype C, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Paganelli G, Severi S, Morse M, Metz DC, Ansquer C, Courbon F, Al-Nahhas A, Baudin E, Giammarile F, Taieb D, Mittra E, Wolin E, O'Dorisio TM, Lebtahi R, Deroose CM, Grana CM, Bodei L, Oberg K, Polack BD, He B, Mariani MF, Gericke G, Santoro P, Erion JL, Ravasi L, Krenning E; NETTER-1 study group. Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study. Eur J Nucl Med Mol Imaging. 2020 Sep;47(10):2372-2382. doi: 10.1007/s00259-020-04709-x. Epub 2020 Mar 2.

Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, Caplin M, Baum RP, Kunz P, Hobday T, Hendifar A, Oberg K, Sierra ML, Thevenet T, Margalet I, Ruszniewski P, Krenning E; NETTER-1 Study Group. Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With 177Lu-Dotatate in the Phase III NETTER-1 Trial. J Clin Oncol. 2018 Sep 1;36(25):2578-2584. doi: 10.1200/JCO.2018.78.5865. Epub 2018 Jun 7.

Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Oberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.

• Responsible Party: Advanced Accelerator Applications
• ClinicalTrials.gov Identifier: NCT01578239
• Other Study ID Numbers: AAA-III-01; 2011-005049-11 ( EudraCT Number ); CAAA601A12301 ( Other Identifier: Novartis )
• First Submitted: April 10, 2012
• First Posted: April 16, 2012
• Results First Submitted: August 29, 2017
• Results First Posted: October 2, 2017
• Last Update Posted: April 4, 2022