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Trial · Interventional

TerminatedPhase 3Results postedRegistry data

Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumours

Short name SPINET

NCTNCT02683941 (opens ClinicalTrials.gov in a new tab)Other idA-US-52030-328Other id2015-004992-62Other id2015
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Terminated
Phase
Phase 3
Enrollment
77 participants (actual)
Sponsor
Ipsen · Industry
Design
Randomized · Double masking
Countries
11 countries

United States, Austria, Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom

Start
6 Mar 2017
Primary completion
28 Feb 2020
Completion
28 Feb 2020
First posted
17 Feb 2016 (estimated)
Last update posted
6 Jul 2022
Conditions
Neuroendocrine Tumors in Lung

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20172018201920202021
  1. Ph 3

    SPINET

    NCT02683941

    6 Mar 2017 to 28 Feb 2020

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This is a Phase 3, prospective, multi-center, randomized, double-blind, study evaluating the efficacy and safety of LAN plus BSC versus placebo plus BSC for the treatment of well-differentiated, metastatic and/or unresectable, typical or atypical bronchopulmonary NETs. This study contains two phases: the Double-Blind (DB) Phase, and the Open Label (OL) Phase. The DB Phase includes: Screening, Baseline and Treatment period. The OL Phase will consist of two periods: Treatment Period and Follow-Up Period. The primary objective will be to describe the antitumour efficacy of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) every 28 days, in terms of progression-free survival (PFS), measured by central review using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria, every 12 weeks, in subjects randomized to LAN with unresectable and/or metastatic well differentiated, typical or atypical bronchopulmonary neuroendocrine tumours. Recent updates of National Cancer Institute Cancer Network (NCCN) \& European Neuroendocrine Tumor Society (ENETS) guidelines recommend SSA in first line for the treatment of locoregional unresectable or metastatic bronchopulmonary NETs as an option beyond 'observation' leading to slow and difficult recruitment in SPINET study. Consequently, it was decided to prematurely stop the recruitment in the SPINET study and to transition all subjects still treated in the double-blind phase to the open label (OL) treatment and follow-up phases following respective country approvals of Amendment #5. The new aim of this Phase 3, multicenter, prospective, randomized placebo-controlled clinical study is to describe the antitumor efficacy and safety of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) in subjects with well-differentiated, metastatic and/or unresectable, typical or atypical, bronchopulmonary NETs.

Interventions

  • Lanreotide (Autogel formulation)Drug
  • PlaceboDrug
  • Best Supportive CareDrug

Arms2

  • Experimental

    Lanreotide (Autogel formulation)

    120mg every 28 days until disease progression, death, or unacceptable toxicity

  • Placebo comparator

    Placebo

    120mg every 28 days until disease progression, death, or unacceptable toxicity during the double-blind phase. The patient may enter open-label phase for treatment with Lanreotide.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Median Progression-Free Survival (PFS) Time in Subjects Randomised to Lanreotide in the Double-Blind Phase or Open-Label Treatment Phase, Assessed by Central Review

    Time frame · Up to a maximum of 33 months

    Registry description

    PFS for subjects randomised in the lanreotide group, assessed by central review using Response Evaluation Criteria In Solid Tumours Version 1.1 (RECIST v1.1) criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during either the double-blind phase, or the open-label treatment phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

Secondary outcomes(9)

  1. Median PFS Time in the Double-Blind Phase, Assessed by Central Review

    Time frame · Up to a maximum of 15 months

    Registry description

    PFS was assessed by central review using RECIST v1.1 criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during the double-blind phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

  2. Median PFS Time in the Double-Blind Phase, Assessed by Local Review

    Time frame · Up to a maximum of 15 months

    Registry description

    PFS was assessed by local review using RECIST v1.1 criteria every 12 weeks, defined as the time from randomisation to disease progression or death from any causes during the double-blind phase. The distribution of PFS times were estimated using the Kaplan-Meier product limit method.

  3. Objective Response Rate (ORR) in the Double-Blind Phase

    Time frame · Up to a maximum of 15 months

    Registry description

    ORR was assessed by central review and local review using RECIST v1.1 criteria every 12 weeks, defined as the percentage of subjects who achieved a best overall response of complete response or partial response in the double-blind phase.

  4. Time to Treatment Failure (TTF) in the Double-Blind Phase

    Time frame · Up to a maximum of 15 months

    Registry description

    TTF was defined as the time from randomisation to disease progression using RECIST v1.1, death, consent withdrawn, an adverse event, protocol deviations, lost to follow-up, the appearance of carcinoid syndrome or other hormone related syndrome necessitating the initiation of SSAs (rescue octreotide and/or long-acting release SSA), or initiation of anticancer treatment in the double-blind phase. The distribution of TTF times were estimated using the Kaplan-Meier product limit method.

  5. Mean Change From Baseline in the Biomarker Chromogranin A (CgA) in the Double-Blind Phase and Open-Label Treatment Phase

    Time frame · Baseline, Weeks 8, 12, 24, and 48, and post-treatment in the double-blind phase (a maximum of 15 months); Baseline, Weeks 12, 24, and 48, and post-treatment in the the open-label treatment phase (a maximum of 33 months)

    Registry description

    Blood samples were collected to determine plasma CgA. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide). The x of upper limit of normal (ULN) was calculated as raw value/ULN.

  6. Percentage of Subjects With a Decrease of CgA ≥30% From Baseline at Week 8 in the Double-Blind Phase and Open-Label Treatment Phase

    Time frame · Baseline and Week 8 in the double-blind phase; Baseline and Week 8 in the open-label treatment phase

    Registry description

    Measured in subjects with an elevated CgA at baseline (≥2 x ULN). Blood samples were collected to determine plasma CgA. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

  7. Mean Changes From Baseline in Quality of Life (QoL), as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Global Health Status/QoL Score

    Time frame · Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months)

    Registry description

    The EORTC QLQ-C30 (V3.0) consisted of 30 questions. The final 2 questions were related to global health status/QoL, with responses requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The global health status/QoL scale ranges in score from 0 to 100. A high score for the global health status/QoL scale represents a high QoL, thus, an increase in score represents an increase in QoL. 95% Clopper-Pearson confidence intervals were estimated using the exact method for binomial distributions. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

  8. Percentage of Subjects Who Experienced QoL Deterioration

    Time frame · Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months)

    Registry description

    QoL deterioration was defined by a decrease from baseline in EORTC QLQ-C30 Global Health Status/QoL Score of at least 10 points. The EORTC QLQ-C30 (V3.0) consisted of 30 questions. The final 2 questions were related to global health status/QoL, with responses requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). The global health status/QoL scale ranges in score from 0 to 100. A high score for the global health status/QoL scale represents a high QoL, thus, an increase in score represents an increase in QoL. 95% Clopper-Pearson confidence intervals were estimated using the exact method for binomial distributions. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide).

  9. Mean Changes From Baseline in Urinary 5-hydroxyindoleacetic Acid (5-HIAA) Levels in the Double-Blind Phase and Open-Label Treatment Phase

    Time frame · Baseline, Weeks 8, 12, 24, and 48, and post-treatment in the double-blind phase (a maximum of 15 months); Baseline, Weeks 12, 24, and 48, and post-treatment in the the open-label treatment phase (a maximum of 33 months)

    Registry description

    Measured in subjects with an elevated 5-HIAA at baseline (≥2 x ULN). The assessment of urinary 5-HIAA required subjects to collect their urine for the 24 hour period prior to the study visit. Baseline was defined as the last non-missing measurement collected prior to the first dose of study treatment (lanreotide). The x of ULN was calculated as raw value/ULN.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMedian· Up to a maximum of 33 months

Median Progression-Free Survival (PFS) Time in Subjects Randomised to Lanreotide in the Double-Blind Phase or Open-Label Treatment Phase, Assessed by Central Review

GroupValue (months)
Overall Study: Lanreotide16.6
Secondary and other outcome results(7)
Secondary outcomeMedian· Up to a maximum of 15 months

Median PFS Time in the Double-Blind Phase, Assessed by Central Review

GroupValue (months)
Double-Blind Phase: Lanreotide16.6
Double-Blind Phase: Placebo13.6
Secondary outcomeMedian· Up to a maximum of 15 months

Median PFS Time in the Double-Blind Phase, Assessed by Local Review

GroupValue (months)
Double-Blind Phase: Lanreotide14.1
Double-Blind Phase: Placebo13.6
Secondary outcomeNumber· Up to a maximum of 15 months

Objective Response Rate (ORR) in the Double-Blind Phase

GroupValue (Percentage of subjects)
Double-Blind Phase: Lanreotide14.00
Double-Blind Phase: Placebo0.00
Secondary outcomeMedian· Up to a maximum of 15 months

Time to Treatment Failure (TTF) in the Double-Blind Phase

GroupValue (months)
Double-Blind Phase: Lanreotide13.3
Double-Blind Phase: Placebo9.8
Secondary outcomeMean· Baseline, Weeks 8, 12, 24, and 48, and post-treatment in the double-blind phase (a maximum of 15 months); Baseline, Weeks 12, 24, and 48, and post-treatment in the the open-label treatment phase (a maximum of 33 months)

Mean Change From Baseline in the Biomarker Chromogranin A (CgA) in the Double-Blind Phase and Open-Label Treatment Phase

GroupValue (x of ULN)Spread
Double-Blind Phase: Lanreotide-213.631293.111
Double-Blind Phase: Placebo0.092.578
Open-Label Treatment Phase: All Subjectsnot posted–
Secondary outcomeNumber· Baseline and Week 8 in the double-blind phase; Baseline and Week 8 in the open-label treatment phase

Percentage of Subjects With a Decrease of CgA ≥30% From Baseline at Week 8 in the Double-Blind Phase and Open-Label Treatment Phase

GroupValue (percentage of subjects)
Double-Blind Phase: Lanreotide63.3
Double-Blind Phase: Placebo7.7
Open-Label Treatment Phase: All Subjects73.7
Secondary outcomeMean· Baseline and post-treatment in the double-blind phase (a maximum of 15 months); Baseline and post-treatment in the open-label treatment phase (a maximum of 33 months)

Mean Changes From Baseline in Quality of Life (QoL), as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Global Health Status/QoL Score

GroupValue (score on a scale)Spread
Double-Blind Phase: Lanreotide-2.718.27
Double-Blind Phase: Placebo-19.417.33
Open-Label Treatment Phase: All Subjects0.019.67

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Double-Blind Phase: LanreotideSubjects received deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and continue to receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. If a subject progressed during the double-blind phase they entered the open-label follow-up phase.2 / 5110 / 5148 / 51
Double-Blind Phase: PlaceboSubjects received deep SC injections of placebo (saline solution 0.9%) Q4 weeks plus BSC in the double-blind phase. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC.0 / 267 / 2625 / 26
Open-Label Treatment PhaseSubjects received deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. Following protocol amendment #5 (28 Jan 2019), all ongoing subjects in the double-blind phase, who had not yet progressed (assessed locally and confirmed centrally) were offered to enter the open-label treatment phase and receive deep SC injections of lanreotide autogel/depot 120 mg Q4 weeks plus BSC. If a subject progressed during the open-label treatment phase they entered the open-label follow-up phase.0 / 401 / 4026 / 40
Open-Label Follow-Up PhaseIf the subject received lanreotide autogel/depot and progressed during the double-blind phase or open-label treatment phase, the subject entered the follow-up phase of the open-label treatment phase and was followed for QoL/survival and all subsequent anticancer treatments received. No intervention was received in the open-label follow-up phase.7 / 260 / 260 / 26

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Have metastatic and/or unresectable pathologically confirmed well-differentiated, typical or atypical neuroendocrine tumor of the bronchopulmonary * Histologic evidence of Well differentiated Neuroendocrine tumors (NETs) of the bronchopulmonary (typical and atypical according to the World Health Organisation (WHO criteria), evaluated locally) * Has a mitotic index \<2 mitoses/2 mm2 for typical carcinoid (TC) and \<10 mitoses/2 mm2 and/or foci of necrosis for atypical carcinoid (AC) * At least one measurable lesion of the disease on imaging (CT or MRI; RECIST 1.1) * Positive Somatostatin receptors (SSTR) imaging Exclusion Criteria: * Poorly differentiated or high grade carcinoma, or patients with neuroendocrine tumors not of bronchopulmonary origin * Has been treated with a Somatostatin analog (SSA) at any time prior to randomization, except if that treatment was for less than 15 days (e.g. peri-operatively) of short acting SSA or one dose of long acting SSA and the treatment was received more than 6 weeks prior to randomization * Has been treated with Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization * Has been treated with more than two lines of cytotoxic chemotherapy or molecular targeted therapy or interferon for bronchopulmonary NET

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