CClinicalTrials.gg
Sign In
CompletedNCT01578239NETTER-1Updated Apr 4, 2022Results posted

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

A Phase 3 interventional study of Octreotide LAR and 177Lu-DOTA0-Tyr3-Octreotate in Carcinoid Tumor of the Small Bowel and Neuroendocrine Tumour, sponsored by Advanced Accelerator Applications. Completed at 39 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-04-04.

Sponsored by Advanced Accelerator Applications · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
231
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This was a multicenter, stratified, open, randomized, comparator-controlled, parallel-group phase III study comparing treatment with Lutathera plus best supportive care (30 mg Octreotide LAR) to treatment with high dose (60 mg) Octreotide LAR in participants with metastasized or locally advanced, inoperable, somatostatin receptor positive, histologically proven midgut carcinoid tumours with progression despite LAR treatment.

Read the detailed description

After the screening period, participants who signed the ICF and were eligible for the study in accordance with the entry criteria were randomly assigned to treatment either Lutathera or Octreotide LAR. Participant randomization was performed according to a centralized permuted block randomization scheme with a balanced ratio (1:1) between the 2 treatment groups, stratified by tumor uptake score and by the length of time that a participant was on a constant dose of Octreotide (=\< 6 versus > 6 months).

Objective tumor assessment in both groups was performed every 12+/-1 weeks from the randomization date according to RECIST Criteria until progression was centrally confirmed:

  1. Any participants with progressive disease (confirmed by central review of CT/MRI scans) ceased the treatment/assessment period and proceeded to the long-term follow-up period for evaluation of survival and long-term safety.

  2. All non-progressive participants continued treatment/assessments until the PFS primary endpoint was met (i.e. 74 evaluable and centrally confirmed disease progressions or death events). Once the Primary End-Point was reached:

    1. Participants who received more than 76 weeks of treatment/assessment, stopped the study treatment (however somatostatin analogues could be received as subsequent treatment as per Investigator's discretion) but continued the long-term follow-up assessment for 5 years overall from the date of randomization of the last participant randomized.
    2. The remaining randomized participants continued in the fixed 76-week treatment/assessment period unless progression occurred, then continued the long-term follow-up assessments for 5 years overall from the date of randomization of the last participant.
02

Conditions studied

  • Carcinoid Tumor of the Small Bowel
  • Neuroendocrine Tumour

Keywords

  • Neuroendocrine tumour
  • 177Lu-Dota0-Tyr3-octreotate
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 231 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Advanced Accelerator Applications is the lead sponsor of 17 studies on the registry; none are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 4 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed).
  2. Ki67 index ≤ 20% (to be centrally confirmed).
  3. Patients on Octreotide LAR at a fixed dose of 20 mg or 30 mg at 3-4 weeks intervals for at least 12 weeks prior to randomization in the study.
  4. Patients ≥18 years of age.
  5. Patients must have progressive disease based on RECIST Criteria, Version 1.1 while receiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Disease progression must be centrally confirmed. In order to make the assessment, two CT (or MRI) scans are required. The oldest scan must not be older than 3 years from the date of randomization. The most recent scan must not be older than 4 weeks from the date of randomization. Both scans must be obtained while the patient is receiving the same fixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) it is acceptable if the oldest scan is obtained within 12 weeks of the patient receiving a fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptable for either scan to be obtained before or during the time a patient receiving a fixed dose of Octreotide LAR has switched to an equivalent dose of short acting Octreotide for up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns to the Octreotide LAR fixed dose after the OctreoScan® has been obtained.
  6. Confirmed presence of somatostatin receptors on all target lesions (for target/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2, RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive OctreoScan® imaging within 24 weeks prior to randomization in the study (to be centrally confirmed). The OctreoScan® should be one that was performed while the patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan® performed while Octreotide LAR treatment-naïve, the patient must have a repeat OctreoScan® performed after 3 months of Octreotide LAR treatments before entering the clinical study to prove that the index lesions or new lesions still meet the criteria for inclusion. It is acceptable to have patients temporarily switched to Octreotide s.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to the same fixed dose of Octreotide LAR prior to the scan.
  7. The tumour uptake observed in each target lesion (for target/non-target/measurable lesions definition see §Appendix 2, Sections 1 and 2, RECIST Criteria, Version 1.1) using OctreoScan® must be ≥ normal liver uptake observed on planar imaging (to be centrally confirmed) (§Appendices 5 and 6).
  8. Karnofsky Performance Score (KPS)>=60.
  9. Presence of at least 1 measurable site of disease.
  10. [Applicable only for France] All patients included in the trial must be affiliated with a social security regime or be a beneficiary of the same in order to be included in the study.

Exclusion criteria

Exclusion Criteria:

  1. Either serum creatinine >150 µmol/L (>1.7 mg/dL), or creatinine clearance \<50 mL/min calculated by the Cockroft Gault method, eventually confirmed by measured creatinine clearance (or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma camera-based) \<50 mL/min (the measured creatinine clearance / GFR is required only as confirmatory exam).
  2. Hb concentration \<5.0 mmol/L (\<8.0 g/dL); WBC \<2x109/L (2000/mm3); platelets \<75x109/L (75x103/mm3).
  3. Total bilirubin >3 x ULN.
  4. Serum albumin \<3.0 g/dL unless prothrombin time is within the normal range.
  5. Pregnancy or lactation.
  6. For female patients of childbearing potential (defined as \< 2 years after last menstruation and not surgically sterile) and male patients, who are not surgically sterile or with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel) as defined in §Appendix 7.
  7. Treatment with >30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to randomization in the study.
  8. Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study.
  9. Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within 12 weeks prior to randomization in the study.
  10. Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to randomization in the study.
  11. Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study. Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to randomization in the study.
  12. Uncontrolled congestive heart failure (NYHA II, III, IV).
  13. Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.
  14. Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of 177Lu-DOTA0-Tyr3-Octreotate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of 177Lu-DOTA0-Tyr3-Octreotate, unless the tumour uptake on target lesions observed by OctreoScan® imaging during continued Octreotide LAR treatment is at least as high as normal liver uptake observed by planar imaging.
  15. Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
  16. Prior external beam radiation therapy to more than 25% of the bone marrow.
  17. Current spontaneous urinary incontinence.
  18. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
  19. Patients who have not provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities.
  20. Patient with known incompatibility to CT Scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded.
  21. Patients who have participated in any therapeutic clinical study/received any investigational agent within the last 30 days are excluded from participation in this trial.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
231 participants (actual)

Study arms

  • Experimental
    177Lu-DOTA0-Tyr3-Octreotate

    * 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.

    Drug: Octreotide LAR · Drug: 177Lu-DOTA0-Tyr3-Octreotate

  • Active comparator
    Octreotide LAR

    * 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.

    Drug: Octreotide LAR

Interventions

  • DrugOctreotide LAR

    In the experimental arm, 30 mg Octreotide LAR treatment was given to the participants until the end of study for symptom control purpose, unless the participant progressed or died. In the active comparator arm, 60 mg Octreotide LAR treatment was given to the participants every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.

    Also known as: SANDOSTATIN LAR, Octreotide

  • Drug177Lu-DOTA0-Tyr3-Octreotate

    Four administrations of 7.4 GBq (200 mCi) 177Lu-DOTA0-Tyr3-Octreotate administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.

    Also known as: Lutathera

06

What researchers measure

Primary outcomes

  1. Progression Free Survival (PFS)

    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

Secondary outcomes

  1. Objective Response Rate (ORR)

    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

  2. Overall Survival (OS)

    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

  3. Rate of Overall Survival (OS)

    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

  4. Time to Tumour Progression (TTP)

    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

  5. Duration of Response (DoR)

    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

  6. Number of Participants With Adverse Events

    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

  7. Change From Baseline in the EORTC QLQ-C30 Questionnaire

    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

  8. Change From Baseline in the EORTC Quality of Life Questionnaire - Neuroendocrine Carcinoid Module (EORTC QLQ-GINET21)

    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

07

Results

Posted Oct 2, 2017

Participant flow

The study was conducted in 41 sites across 8 countries.

Treatment Period
Participant flow — Treatment Period
Milestone177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Started117114
Full analysis set (fas)117114
Safety analysis set (saf)111112
Fas-entered long-term follow-up10199
Completed5013
Not completed67101
Withdrew: Progressive disease1964
Withdrew: Physician decision1717
Withdrew: Adverse event1310
Withdrew: Non-compliance20
Withdrew: Withdrawal by subject109
Withdrew: Other61
Long-term Follow-Up Period
Participant flow — Long-term Follow-Up Period
Milestone177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Started10199
Completed2419
Not completed7780
Withdrew: Death6964
Withdrew: Consent withdrawal410
Withdrew: Lost to follow-up24
Withdrew: Other22

Outcome measures

PrimaryProgression Free Survival (PFS)

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
Reported as:
Median · months
Progression Free Survival (PFS)
months177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Progression Free Survival (PFS)NA (NA to NA)8.5 (5.8 to 9.1)
Statistical analysis
  • 177Lu-DOTA0-Tyr3-Octreotate vs Octreotide LAR · Log Rank · p = <0.0001 (Derived from a two-sided test between the two groups) · Hazard ratio (hr): 0.177 · 95% CI 0.108 to 0.289Hazard ratio is expressed as Lu-DOTA-Tyr-Octreotate / Octreotide LAR and estimated from the corresponding Cox model.
SecondaryObjective Response Rate (ORR)

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
Reported as:
Number · Percentage of Participants
Objective Response Rate (ORR)
Percentage of Participants177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Objective Response Rate (ORR)14.7 (7.8 to 21.6)4.0 (0.2 to 7.8)
Statistical analysis
  • 177Lu-DOTA0-Tyr3-Octreotate vs Octreotide LAR · Fisher Exact · p = 0.0141
SecondaryOverall Survival (OS)

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
Reported as:
Median · Months
Overall Survival (OS)
Months177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Overall Survival (OS)48.0 (37.4 to 55.2)36.3 (25.9 to 51.7)
Statistical analysis
  • 177Lu-DOTA0-Tyr3-Octreotate vs Octreotide LAR · Log Rank · p = 0.3039 · Hazard ratio (hr): 0.84 · 95% CI 0.60 to 1.17
SecondaryRate of Overall Survival (OS)

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
Reported as:
Number · Percentage of Survival Estimates
Rate of Overall Survival (OS)
Percentage of Survival Estimates177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
12 months91.0 (84.0 to 95.1)79.7 (70.8 to 86.1)
24 months76.0 (66.7 to 83.0)62.7 (52.6 to 71.2)
36 months61.4 (51.4 to 69.9)50.1 (40.0 to 59.4)
48 months49.5 (39.5 to 58.6)41.8 (31.8 to 51.4)
60 months37.1 (27.8 to 46.4)35.4 (25.7 to 45.2)
Statistical analysis
  • 177Lu-DOTA0-Tyr3-Octreotate vs Octreotide LAR · Log Rank · p = 0.3039 · Cox proportional hazard: 0.84 · 95% CI 0.60 to 1.17Hazard Ratio of Lu-DOTA-Tyr-Octreotate vs. Octreotide LAR
SecondaryTime to Tumour Progression (TTP)

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
Reported as:
Median · Months
Time to Tumour Progression (TTP)
Months177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Time to Tumour Progression (TTP)NA (NA to NA)8.7 (6.0 to 11.1)
Statistical analysis
  • 177Lu-DOTA0-Tyr3-Octreotate vs Octreotide LAR · Log Rank · p = <0.0001 · Hazard ratio (hr): 0.137 · 95% CI 0.077 to 0.242
SecondaryDuration of Response (DoR)

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
Reported as:
Median · Months
Duration of Response (DoR)
Months177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Duration of Response (DoR)NA (2.8 to NA)1.9 (1.9 to NA)
SecondaryNumber of Participants With Adverse Events

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
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events
Participants177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Adverse Events (AEs)10590
Serious Adverse Events (SAEs)4031
Deaths during treatment period45
Deaths during follow-up period6663
SecondaryChange From Baseline in the EORTC QLQ-C30 Questionnaire

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
Reported as:
Mean · Scores on a scale
Change From Baseline in the EORTC QLQ-C30 Questionnaire
Scores on a scale177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Physical functioning: chg from BL @ wk 72 (n=33,11)3.232 ± 12.4857-4.242 ± 10.0101
Physical functioning: chg from BL @ wk 120 (n=2,0)-3.333 ± 4.7140—
Role functioning: chg from BL @ wk 72 (n=33,11)5.051 ± 33.1989-3.030 ± 16.3608
Role functioning: chg from BL @ wk 120 (n=2,0)8.333 ± 11.7851—
Emotional functioning: chg from BL @ wk 72 (n=33,11)7.744 ± 22.66026.061 ± 17.9083
Emotional functioning: chg from BL @ wk 120 (n=2,0)12.500 ± 5.8926—
Cognitive functioning: chg from BL @ wk 72 (n=33,11)5.556 ± 15.95711.515 ± 13.8535
Cognitive functioning: chg from BL @ wk 120 (n=2,0)16.667 ± 23.5702—
Social functioning: chg from BL @ wk 72 (n=33,11)8.586 ± 28.9039-7.576 ± 18.8025
Social functioning: chg from BL @ wk 120 (n=2,0)8.333 ± 35.3553—
Global Health Status/QoL: chg from BL @ wk 72 (n=33,11)5.556 ± 21.41551.515 ± 10.4205
Global Health Status/QoL: chg from BL @ wk 120 (n=2,0)-16.667 ± 0.0000—
Fatigue: chg from BL @ wk 72 (n=33,11)-7.239 ± 24.7084-2.020 ± 13.8939
Fatigue: chg from BL @ wk 120 (n=2,0)11.111 ± 0.0000—
Nausea & Vomiting: chg from BL @ wk 72 (n=33,11)-4.545 ± 15.1799-4.545 ± 7.7850
Nausea & Vomiting: chg from BL @ wk 120 (n=2,0)0.000 ± 0.0000—
Pain: chg from BL @ wk 72 (n=33,11)-8.586 ± 22.4850-3.030 ± 10.0504
Pain: chg from BL @ wk 120 (n=2,0)0.000 ± 23.5702—
Dyspnoea: chg from BL @ wk 72 (n=33,11)-3.030 ± 22.61343.030 ± 27.7070
Dyspnoea: chg from BL @ wk 120 (n=2,0)0.000 ± 0.0000—
Insomnia: chg from BL @ wk 72 (n=33,11)0.000 ± 26.35236.061 ± 29.1288
Insomnia: chg from BL @ wk 120 (n=2,0)33.333 ± 47.1405—
Appetite loss: chg from BL @ wk 72 (n=33,11)-8.081 ± 20.46399.091 ± 21.5557
Appetite loss: chg from BL @ wk 120 (n=2,0)0.000 ± 0.0000—
Constipation: chg from BL @ wk 72 (n=33,11)0.000 ± 18.63390.000 ± 14.9071
Constipation: chg from BL @ wk 120 (n=2,0)0.000 ± 0.0000—
Diarrhoea: chg from BL @ wk 72 (n=33,11)-12.121 ± 36.1499-3.030 ± 27.7070
Diarrhoea: chg from BL @ wk 120 (n=2,0)-16.667 ± 23.5702—
Financial difficulties: chg from BL @ wk 72 (n=33,11)-7.071 ± 33.07986.061 ± 20.1008
Financial difficulties: chg from BL @ wk 120 (n=2,0)-16.667 ± 70.7107—
SecondaryChange From Baseline in the EORTC Quality of Life Questionnaire - Neuroendocrine Carcinoid Module (EORTC QLQ-GINET21)

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
Reported as:
Mean · Scores on a scale
Change From Baseline in the EORTC Quality of Life Questionnaire - Neuroendocrine Carcinoid Module (EORTC QLQ-GINET21)
Scores on a scale177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Endocrine scale: chg from BL @ wk 72 (n=33,11)-8.754 ± 20.1762-11.111 ± 21.0819
Endocrine scale: chg from BL @ wk 120 (n=2,0)0.000 ± 0.0000—
G.I. scale: chg from BL @ wk 72 (n=33,11)-2.727 ± 15.30832.424 ± 10.0101
G.I. scale: chg from BL @ wk 120 (n=2,0)-13.333 ± 0.0000—
Treatment scale: chg from BL @ wk 72 (n=21,5)-8.995 ± 14.95630.000 ± 11.1111
Treatment scale: chg from BL @ wk 120 (n=1,0)-16.667 ± NA—
Social function scale: chg from BL @ wk 72 (n=33,11)-7.576 ± 23.3985-7.576 ± 21.1217
Social function scale: chg from BL @ wk 120 (n=2,0)11.111 ± 0.0000—
Diseases rel. worries scale: chg from BL @ wk 72 (n=33,11)-6.061 ± 27.92891.010 ± 33.7765
Diseases rel. worries scale: chg from BL @ wk 120 (n=2,0)33.333 ± 31.4270—
Muscle/Bone pain symptom: chg from BL @ wk 72 (n=33,10)-5.051 ± 33.4594-16.667 ± 36.0041
Muscle/Bone pain symptom: chg from BL @ wk 120 (n=2,0)-16.667 ± 23.5702—
Sexual function: chg from BL @ wk 72 (n=21,7)6.349 ± 40.303114.286 ± 17.8174
Sexual function: chg from BL @ wk 120 (n=2,0)50.000 ± 70.7107—
Information/Communication: chg from BL @ wk 72 (n=33,11)-4.040 ± 26.0309-12.121 ± 30.8139
Information/Communication: chg from BL @ wk 120 (n=2,0)0.000 ± 0.0000—
Body image: chg from BL @ wk 72 (n=33,11)-4.040 ± 18.1766-3.030 ± 17.9787
Body image: chg from BL @ wk 120 (n=2,0)16.667 ± 23.5702—

Adverse events

Collected over From informed consent signature through study completion reached at final safety cutoff date on 18July2021, assessed up to approximately 101 Months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
177Lu-DOTA0-Tyr3-Octreotate70/111 (63.1%)40/111 (36%)105/111 (94.6%)
Octreotide LAR68/112 (60.7%)31/112 (27.7%)90/112 (80.4%)
Most frequent serious events
Showing 10 of 88
Most frequent serious events
Event177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/1115/112
Acute kidney injuryRenal and urinary disorders4/1111/112
Abdominal painGastrointestinal disorders3/1111/112
LymphopeniaBlood and lymphatic system disorders2/1110/112
VomitingGastrointestinal disorders2/1112/112
General physical health deteriorationGeneral disorders2/1112/112
Femur fractureInjury, poisoning and procedural complications2/1110/112
Oesophageal adenocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/1110/112
Abdominal pain lowerGastrointestinal disorders0/1112/112
Small intestinal obstructionGastrointestinal disorders1/1112/112
Most frequent other events
Showing 10 of 50
Most frequent other events
Event177Lu-DOTA0-Tyr3-OctreotateOctreotide LAR
NauseaGastrointestinal disorders74/11113/112
VomitingGastrointestinal disorders59/1119/112
FatigueGeneral disorders43/11130/112
DiarrhoeaGastrointestinal disorders32/11120/112
Abdominal painGastrointestinal disorders28/11121/112
Decreased appetiteMetabolism and nutrition disorders24/11112/112
HeadacheNervous system disorders21/1116/112
DizzinessNervous system disorders19/11110/112
AnaemiaBlood and lymphatic system disorders18/1118/112
LymphopeniaBlood and lymphatic system disorders18/1110/112

Baseline characteristics

Age, Continuous
Age, Continuous(years)177Lu-DOTA0-Tyr3-OctreotateOctreotide LARTotal
Mean63.4 ± 9.3464.0 ± 9.8063.7 ± 9.55
Sex: Female, Male
Sex: Female, Male(Participants)177Lu-DOTA0-Tyr3-OctreotateOctreotide LARTotal
Female5460114
Male6354117
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)177Lu-DOTA0-Tyr3-OctreotateOctreotide LARTotal
Asian101
Black or African American5510
Hispanic639
White9396189
Other011
Not Applicable12921
08

Study locations

39 sites
  • Cedars-Sinai Medical Center Samuel Oschin Cancer Center
    Los Angeles, California 90048, United States
  • Stanford Cancer Center
    Palo Alto, California 94304, United States
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Northwestern Medical Faculty Foundation
    Chicago, Illinois 60611-3015, United States
  • University of Iowa Hospitals and Clinics
    Iowa City, Iowa 52242, United States
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Kettering Medical Center
    Kettering, Ohio 45429, United States
  • Perelman Center for Advanced Medicine
    Philadelphia, Pennsylvania 19104, United States
  • Henry-Joyce Cancer Clinic
    Nashville, Tennessee 37232, United States
  • University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Excel Diagnostics and Nuclear Oncology Center
    Houston, Texas 77042, United States
  • Digestive Oncology, Leuven Cancer Institute
    Leuven, Brabant Flamand 3000, Belgium
  • Institut Gustave Roussy
    Villejuif Cedex, Ile De France 94805, France
  • Institut Claudius Regaud
    Toulouse, Midi-Pyrénées 31100, France
  • Hotel Dieu/CHU Nantes
    Nantes, Pays De La Loire 44093, France
  • Hôpital la Timone /CHU Marseille
    Marseille, Provence-Alpes-Côte d'Azur 13385, France
  • Centre Hospitalier Lyon-Sud
    Lyon, Rhône-Alpes 69002, France
  • Hôpital Beaujon AP-HP
    Clichy Cedex, 92118, France
  • Klinikum Rechts Isar, Nuclear Medicine
    Munich, Bayern 81675, Germany
  • Universitätsmedizin Mainz, Medizinische Klinik I Schwerpunkt Endokrinologie
    Mainz, Rheinland-Pfalz 55131, Germany
  • Zentralklinik Bad Berka
    Bad Berka, Thüringen 99437, Germany
  • Charité, Virchow-Klinikum, Gastroentrology, Hepatology & Endocrinology
    Berlin, 13353, Germany
  • Istituto Oncologico Romagnolo per lo Studio dei Tumori
    Meldola, Emilia-Romagna 47014, Italy
  • IEO Istituto Europeo di Oncologia
    Milano, Lombardia 20141, Italy
  • Presidio Osp. Di Macerata
    Macerata, Marche 62100, Italy
  • Azienda Ospedaliero - Universitaria Pisana (Presidio Ospedaliero S. Chiara)
    Pisa, Toscana 56126, Italy
  • Fondazione IRCCS Istituto Nazionale dei Tumori
    Milano, 20133, Italy
  • Università "Sapienza" di Roma, Facoltà di Medicina e Psicologia, Ospedale S. Andrea-Roma
    Roma, 00189, Italy
  • Centro Hospitalar e Universitario de Coimbra
    Coimbra, Centro 3000-075, Portugal
  • Instituto Português de Oncologia
    Porto, Norte 4200-072, Portugal
  • University Hospital of Bellvitge
    Hospitalet de Llobregat (Barcelona), Cataluña 08907, Spain
  • Ramon y Cajal University Hospital
    Madrid, 28034, Spain
  • University of Oxford
    Oxford, South East England OX3 7LE, United Kingdom
  • Beatson Oncology Centre
    Glasgow, G12 0YN, United Kingdom
  • Royal Free Hospital
    London, NW3 2QG, United Kingdom
  • Imperial College Healthcare Trust, Hammersmith Hospital
    London, W12 0HS, United Kingdom
  • The Christie NHS foundation Trust
    Manchester, M20 4BX, United Kingdom
09

References and documents

Publications

  • 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. doi: 10.1016/S1470-2045(22)00028-6. PubMed 34793718 ↗
  • 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. PubMed 32123969 ↗
  • 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. PubMed 29878866 ↗
  • 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. PubMed 28076709 ↗

Individual participant data

Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 4, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01578239
Lead sponsor
Advanced Accelerator Applications
Responsible party
Sponsor
First posted
Apr 16, 2012
Start date
Sep 6, 2012
Primary completion
Jul 31, 2015
Completion
Jan 18, 2021
Results posted
Oct 2, 2017
Last update
Apr 4, 2022

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Neoplasms→

Other studies from this sponsor

Advanced Accelerator Applications

Start the discussion