Last reviewed · How we verify

NCT02651987: CLARINET FORTE

Efficacy and Safety Study in Pancreatic or Midgut Neuroendocrine Tumours Having Progressed Radiologically While Previously Treated With Lanreotide Autogel® 120 mg

Completed Phase 2 Results posted Last updated 3 October 2022
What this trial tests

Phase 2 trial testing Lanreotide autogel 120 mg in Pancreatic Tumours in 99 participants. Completed in 24 October 2019.

Timeline
15 December 2015
Primary endpoint
16 October 2019
24 October 2019

Quick facts

Lead sponsorIpsen
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment99
Start date15 December 2015
Primary completion16 October 2019
Estimated completion24 October 2019
Sites32 locations across Denmark, France, Italy, Netherlands, Belgium, Ireland, United Kingdom, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Ipsen — full company profile →

Who can join

18 and older, any sex, with Pancreatic Tumours or Midgut Neuroendocrine Tumours. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Median Progression Free Survival (PFS) Primary · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

PFS was defined as the time from first injection of lanreotide Autogel® 120 mg every 14 days to progression or death. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured by independent central review using the same imaging technique (computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\]) for each subject throughout the study. The median PFS time was estimated using the Kaplan Meier method for each cohort.

GroupValue95% CI
PanNET Cohort5.65.5 – 8.3
Midgut NET Cohort8.35.6 – 11.1
Median Time to Progression Secondary · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

Time to Progression was defined as time from first injection of lanreotide Autogel® 120 mg every 14 days to progression. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured by independent central review using the same imaging technique (CT scan or MRI) for each subject throughout the study. Median time to progression was estimated using the Kaplan Meier method for each cohort.

GroupValue95% CI
PanNET Cohort5.65.5 – 8.3
Midgut NET Cohort8.78.3 – 13.9
Percentage of Subjects Alive and Progression Free Secondary · Weeks 12, 24, 36, 48, 60 (for both cohorts) and Weeks 72, 84 and 96 (for midgut NET cohort)

The percentage of subjects alive and progression-free was assessed throughout the study up to Week 60 for the panNET cohort and Week 96 for the midgut cohort. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks measured by independent central review using the same imaging technique (CT scan or MRI) for each subject throughout the study. The percentage of subjects alive and progression free was estimated using the Kaplan Meier method for each cohort.

Week 12
GroupValue95% CI
PanNET Cohort93.380.7 – 97.8
Midgut NET Cohort91.879.7 – 96.9
Week 24
GroupValue95% CI
PanNET Cohort64.448.7 – 76.5
Midgut NET Cohort65.350.3 – 76.8
Week 36
GroupValue95% CI
PanNET Cohort37.823.9 – 51.6
Midgut NET Cohort59.244.2 – 71.4
Week 48
GroupValue95% CI
PanNET Cohort28.516.2 – 42.1
Midgut NET Cohort38.324.8 – 51.6
Week 60
GroupValue95% CI
PanNET Cohort20.79.0 – 35.7
Midgut NET Cohort36.122.9 – 49.5
Week 72
GroupValue95% CI
Midgut NET Cohort29.817.6 – 42.9
Week 84
GroupValue95% CI
Midgut NET Cohort27.515.7 – 40.5
Week 96
GroupValue95% CI
Midgut NET Cohort25.213.9 – 38.1
Overall Survival Secondary · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

Overall survival was defined as the time in months from the first injection of lanreotide Autogel® 120 mg every 14 days to death due to any cause. Median overall survival was estimated using the Kaplan Meier method for each cohort.

GroupValue95% CI
PanNET CohortNANA – NA
Midgut NET CohortNANA – NA
Objective Response Rate (ORR) Secondary · Weeks 12, 24, 36, 48, 60 (for both cohorts) and Weeks 72, 84, and 96 (for midgut cohort)

The ORR was defined as the percentage of subjects who achieve either complete response (CR) or partial response (PR) according to RECIST v1.0 criteria. ORR was evaluated every 12 weeks and results are presented for each cohort.

Week 12
GroupValue95% CI
PanNET Cohort0.00.0 – 7.4
Midgut NET Cohort0.00.0 – 7.0
Week 24
GroupValue95% CI
PanNET Cohort0.00.0 – 7.4
Midgut NET Cohort0.00.0 – 7.0
Week 36
GroupValue95% CI
PanNET Cohort0.00.0 – 7.4
Midgut NET Cohort0.00.0 – 7.0
Week 48
GroupValue95% CI
PanNET Cohort0.00.0 – 7.4
Midgut NET Cohort0.00.0 – 7.0
Week 60
GroupValue95% CI
PanNET Cohort0.00.0 – 7.4
Midgut NET Cohort2.00.0 – 10.4
Week 72
GroupValue95% CI
Midgut NET Cohort3.90.5 – 13.5
Week 84
GroupValue95% CI
Midgut NET Cohort2.00.0 – 10.4
Week 96
GroupValue95% CI
Midgut NET Cohort2.00.0 – 10.4
Disease Control Rate (DCR) Secondary · Weeks 24 and 48

The DCR was defined as the percentage of subjects who achieved CR plus PR plus Stable Disease (SD), evaluated according to RECIST v1.0 criteria. The DCR at Weeks 24 and 48 is presented for each cohort.

Week 24
GroupValue95% CI
PanNET Cohort43.829.5 – 58.8
Midgut NET Cohort58.844.2 – 72.4
Week 48
GroupValue95% CI
PanNET Cohort22.912.0 – 37.3
Midgut NET Cohort33.320.8 – 47.9
Best Overall Response Rate Secondary · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

Best overall response was defined as the best response recorded from the initiation of treatment until disease progression, according to RECIST v1.0 evaluation. The percentage of subjects in each response category and those who were non-evaluable (i.e. with no tumour assessment after the start of study treatment) throughout the study are presented for each cohort.

CR
GroupValue95% CI
PanNET Cohort0.00.0 – 7.4
Midgut NET Cohort0.00.0 – 7.0
PR
GroupValue95% CI
PanNET Cohort0.00.0 – 7.4
Midgut NET Cohort3.90.5 – 13.5
SD
GroupValue95% CI
PanNET Cohort66.751.6 – 79.6
Midgut NET Cohort68.654.1 – 80.9
PD
GroupValue95% CI
PanNET Cohort31.318.7 – 46.3
Midgut NET Cohort23.512.8 – 37.5
Not evaluable
GroupValue95% CI
PanNET Cohort0.00.0 – 7.4
Midgut NET Cohort2.00.0 – 10.4
Median Duration of Stable Disease Secondary · From Day 1 up to Week 60 for the panNET cohort and Week 103 for the midgut NET cohort

Median duration of SD was the time from first injection of lanreotide Autogel® 120 mg every 14 days until the first occurrence of PD by central assessment. Disease progression was assessed by tumour response evaluation according to RECIST v1.0, every 12 weeks, measured using the same imaging technique (CT scan or MRI) for each subject throughout the study. Median duration of stable disease was estimated using the Kaplan Meier method for each cohort.

GroupValue95% CI
PanNET Cohort8.38.0 – 13.8
Midgut NET Cohort13.88.6 – NA
Factors Associated With PFS Secondary · Screening/Baseline (Day 1)

A univariate cox proportional hazards model was used to assess whether the following factors were associated with PFS: * Hepatic tumour load: \>25% versus reference ≤25% * Tumour Grade: Grade 2 versus reference Grade 1, * Previous surgery of the primary tumour: No versus reference Yes, * Proliferation index Ki67: ≥10% versus reference \<10% * Duration of treatment with lanreotide Autogel® 120 mg every 28 days by category: ≥median value versus reference \<median value, * Age by category: ≥65 years versus reference \<65 years, * Time from diagnosis to study entry by category: ≥3 years versus re

Hepatic tumour load: >25% Vs ≤25%
GroupValue95% CI
PanNET Cohort0.960.40 – 2.32
Midgut NET Cohort1.540.70 – 3.40
Tumour Grade: 2 Vs 1
GroupValue95% CI
PanNET Cohort0.680.32 – 1.45
Midgut NET Cohort0.900.46 – 1.77
Previous surgery: No Vs Yes
GroupValue95% CI
PanNET Cohort1.040.53 – 2.04
Midgut NET Cohort2.140.83 – 5.52
Ki67: ≥10% Vs <10%
GroupValue95% CI
PanNET Cohort3.601.39 – 9.32
Midgut NET Cohort2.260.67 – 7.60
Duration of treatment with lanreotide Autogel® 120 mg every 28 days: ≥median Vs <median
GroupValue95% CI
PanNET Cohort0.680.34 – 1.34
Midgut NET Cohort0.760.40 – 1.47
Age: ≥65 years Vs <65 years
GroupValue95% CI
PanNET Cohort1.550.79 – 3.06
Midgut NET Cohort1.150.58 – 2.31
Time from diagnosis: ≥3 years Vs <3 years
GroupValue95% CI
PanNET Cohort0.490.25 – 0.96
Midgut NET Cohort0.940.49 – 1.82
Time between CT scans: ≥12 months Vs <12 months
GroupValue95% CI
PanNET Cohort0.470.24 – 0.94
Midgut NET Cohort0.720.37 – 1.39
Mean Change From Baseline in Number of Stools and Flushing Episodes Secondary · Baseline (Day 1), Weeks 8,12, 48 and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET cohort)

Symptom control was measured by the total number of stools (diarrhoea) and flushing episodes during the 7 days prior to the visit, reported orally by the subject to the investigator. The mean change from baseline in number of stools and flushing episodes reported at each visit is presented for each cohort.

Stools - Week 8
GroupValue95% CI
PanNET Cohort1.0± 5.5
Midgut NET Cohort-1.0± 8.2
Stools - Week 12
GroupValue95% CI
PanNET Cohort-1.2± 7.9
Midgut NET Cohort0.7± 2.5
Stools - Week 48
GroupValue95% CI
PanNET Cohort-1.0± 0.0
Midgut NET Cohort3.4± 4.8
Stools - End of Study
GroupValue95% CI
PanNET Cohort0.5± 5.4
Midgut NET Cohort-1.2± 12.2
Flushing - Week 8
GroupValue95% CI
PanNET Cohort0.7± 2.1
Midgut NET Cohort-3.3± 8.3
Flushing - Week 12
GroupValue95% CI
PanNET Cohort-1.0± 0.0
Midgut NET Cohort1.5± 10.0
Flushing - Week 48
GroupValue95% CI
PanNET Cohort-1.0± 0.0
Midgut NET Cohort-1.5± 2.1
Flushing - End of Study
GroupValue95% CI
PanNET Cohort0.0± 1.4
Midgut NET Cohort-0.5± 6.2
Mean Change From Baseline in QoL Measured Using EORTC, QLQ-C30 v3.0 (Global Health Status Sub-score) Secondary · Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort)

Subjects were instructed to complete the 30 questions in the EORTC-QLQ-C30 v3.0 questionnaire at baseline and every 12 weeks throughout the study. The global health status sub-score was assessed using the last 2 questions which represented subject's assessment of overall health \& QoL. Each question was coded on a 7-point scale (1=very poor to 7=excellent). The sub-score was transformed to range from 0-100, with a high score for global health status representing a high QoL. The mean change from baseline in the transformed global health status are presented for the end of study/early withdrawa

GroupValue95% CI
PanNET Cohort-0.38± 15.32
Midgut NET Cohort-1.33± 17.13
Overall-0.89± 16.14
Mean Change From Baseline in EQ-5D-5L v1.0 Questionnaire (Descriptive System) Secondary · Baseline (Day 1) and end of study (approximately 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort)

Subjects were instructed to complete the EQ-5D-5L descriptive system at baseline and every 12 weeks throughout the study. The EQ-5D-5L descriptive system comprised the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The EQ-5D-5L health states, defined by the EQ-5D-5L descriptive system, was converted into a single index value with scores ranging from 0 (no problems) to 1 (extreme problems). The mean change from baseline at the

GroupValue95% CI
PanNET Cohort-0.04± 0.12
Midgut NET Cohort0.00± 0.11
Overall-0.02± 0.12

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment emergent adverse events were recorded from the first dose of lanreotide Autogel® 120 mg on Day 1 until 28 days after the last treatment. Overall time frame of up to a maximum of 64 weeks for panNET cohort and 108 weeks for midgut NET (and overall) cohort.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PanNET Cohort
Serious: 5/48 (10%)
Deaths: 1/48
Midgut NET Cohort
Serious: 13/51 (25%)
Deaths: 3/51
Overall Subjects
Serious: 18/99 (18%)
Deaths: 4/99

Serious adverse events (20 terms)

ReactionSystemPanNET CohortMidgut NET CohortOverall Subjects
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Cardiac failureCardiac disorders
Pulseless electrical activityCardiac disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
AstheniaGeneral disorders
Chest painGeneral disorders
General physical health deteriorationGeneral disorders
Anaphylactic reactionImmune system disorders
PeritonitisInfections and infestations
Viral infectionInfections and infestations
Craniocerebral injuryInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Spinal fractureInjury, poisoning and procedural complications
Bone neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Spinal cord compressionNervous system disorders
SyncopeNervous system disorders
HypotensionVascular disorders
Other adverse events (207 terms — click to expand)

ReactionSystemPanNET CohortMidgut NET CohortOverall Subjects
DiarrhoeaGastrointestinal disorders
Abdominal painGastrointestinal disorders
FatigueGeneral disorders
NasopharyngitisInfections and infestations
NauseaGastrointestinal disorders
FlushingVascular disorders
HypertensionVascular disorders
VomitingGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
AstheniaGeneral disorders
DizzinessNervous system disorders
FlatulenceGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
HeadacheNervous system disorders
Abdominal distensionGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
SteatorrhoeaGastrointestinal disorders
InfluenzaInfections and infestations
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
Influenza like illnessGeneral disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Lower respiratory tract infectionInfections and infestations
Blood alkaline phosphatase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Chest painGeneral disorders
MalaiseGeneral disorders
Peripheral swellingGeneral disorders
CholelithiasisHepatobiliary disorders
CystitisInfections and infestations
Alanine aminotransferase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Weight decreasedInvestigations
HypocalcaemiaMetabolism and nutrition disorders
Joint swellingMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pulmonary embolism, Cardiac failure, Pulseless electrical activity, Abdominal pain, Diarrhoea, Intestinal obstruction, Asthenia, Chest pain.

Data from ClinicalTrials.gov NCT02651987 adverse events section.

Sponsor's own description

This study aims to explore the efficacy and safety of lanreotide Autogel® 120 mg administered every 14 days in subjects with grade 1 or 2, metastatic or locally advanced, unresectable pancreatic or intestinal neuroendocrine tumours (NETs) once they have progressed on the standard dose of lanreotide Autogel® 120 mg every 28 days.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms.
    Hofland J, Kaltsas G, de Herder WW. · · 2020 · cited 121× · PMID 31555796 · DOI 10.1210/endrev/bnz004
  2. Targeted Systemic Treatment of Neuroendocrine Tumors: Current Options and Future Perspectives.
    Herrera-Martínez AD, Hofland J, Hofland LJ, Brabander T, et al · · 2019 · cited 63× · PMID 30560479 · DOI 10.1007/s40265-018-1033-0
  3. Clinical, Diagnostic, and Treatment Characteristics of &lt;i&gt;SDHA&lt;/i&gt;-Related Metastatic Pheochromocytoma and Paraganglioma.
    Jha A, Jha A, de Luna K, Balili CA, et al · · 2019 · cited 46× · PMID 30854332 · DOI 10.3389/fonc.2019.00053
  4. Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs).
    Megdanova-Chipeva VG, Lamarca A, Backen A, McNamara MG, et al · · 2020 · cited 19× · PMID 32708210 · DOI 10.3390/cancers12071988
  5. Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors.
    Pusceddu S, Rossi RE, Torchio M, Prinzi N, et al · · 2020 · cited 12× · PMID 32752158 · DOI 10.3390/jcm9082468
  6. Advances in medical treatment for pancreatic neuroendocrine neoplasms.
    Li YL, Cheng ZX, Yu FH, Tian C, et al · · 2022 · cited 4× · PMID 35721885 · DOI 10.3748/wjg.v28.i20.2163
  7. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives.
    Merola E, Michielan A, Rozzanigo U, Erini M, et al · · 2022 · cited 4× · PMID 35317548 · DOI 10.4240/wjgs.v14.i2.78
  8. High-dose Somatostatin Analogues for Progressive Neuroendocrine Tumours.
    Sharp AJ, Hayes AR, Grossman A. · · 2020 · cited 2× · PMID 33117438 · DOI 10.17925/ee.2020.16.2.93

Verify or expand the search:

Other Ipsen trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02651987.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing