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Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumors (SPINET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02683941
Recruitment Status : Active, not recruiting
First Posted : February 17, 2016
Last Update Posted : March 4, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Tracking Information
First Submitted Date  ICMJE September 21, 2015
First Posted Date  ICMJE February 17, 2016
Last Update Posted Date March 4, 2019
Actual Study Start Date  ICMJE February 2016
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
Progression-Free Survival (PFS), assessed by central review using RECIST v1.1 criteria [ Time Frame: From randomisation up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
PFS measured by central review using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria, every 12 weeks, defined as the time from randomization to disease progression or death from any causes
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02683941 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2016)
  • Objective Response Rate (ORR): best overall response of complete response (CR) or partial response (PR) measured by RECIST v1.1 criteria [ Time Frame: Baseline, week 12, 24, 36, 48, 60, 72, early withdrawal visit (may occur at any time post treatment up to 72 weeks) ]
  • Overall Survival, defined as the time from randomization to death from any causes [ Time Frame: From randomisation up to 18 months (approximately) after the last patient is randomised ]
    The analysis will occur when the target number of events (175 progression/death events) among the two treatment groups has been observed.
  • Time to treatment failure, defined as the time from randomization to disease progression, withdrawal for any reason, or death using RECIST v1.1. assessment [ Time Frame: From randomisation up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
    The analysis will occur when the target number of events (175 progression/death events) among the two treatment groups has been observed.
  • Mean changes from Baseline in the biomarker chromogranin A (CgA) [ Time Frame: Baseline, week 8, 12, 24, 36,48, 60, 72, early withdrawal visit (may occur at any time post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Proportion of subjects with a decrease of CgA ≥30% at week 8 in the population of subjects with an elevated CgA (≥2 x ULN) at Baseline [ Time Frame: Baseline, week 8 ]
  • Change in Quality of Life (QoL), as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 [ Time Frame: Baseline, week 12, 24, 36, 48, 60, 72, early withdrawal visit (may occur at any time post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Time to QoL deterioration, defined by a decrease from baseline in EORTC Quality of Life Questionnaire C30 (QLQ-C30) score of at least 10 points [ Time Frame: Baseline, week 12, 24, 36, 48, 60, 72, early withdrawal visit (may occur at any time post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Mean changes from Baseline in urinary 5-HIAA levels in subjects with elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) (≥2 x Upper limit of normal range) at Baseline [ Time Frame: Baseline, week 8, 12, 24, 36, 48, 60, 72 and early withdrawal visit (may occur at any time post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Plasma Concentration of lanreotide in serum [ Time Frame: Baseline, week 24, week 36, early withdrawal visit (may occur at any time post treatment up to 72 weeks) ]
    Pharmacokinetics (PK) of LAN
Original Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
  • PFS, assessed by local review using RECIST v1.1 criteria [ Time Frame: From randomisation up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
    The analysis will occur when the target number of events (175 progression/death events) among the two treatment groups has been observed.
  • Time to treatment failure, defined as the time from randomization to disease progression, withdrawal for any reason, or death using RECIST v1.1. assessment [ Time Frame: From randomisation up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
    The analysis will occur when the target number of events (175 progression/death events) among the two treatment groups has been observed.
  • Mean changes from Baseline in the biomarker chromogranin A (CgA) [ Time Frame: Baseline, week 8, 12, 24, 36,48, 60, 72, early withdrawal visit (may occur at anytime post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Proportion of subjects with a decrease of CgA ≥30% at week 8 in the population of subjects with an elevated CgA (≥2 x ULN) at Baseline [ Time Frame: Baseline, week 8 ]
  • Disease Control Rate (DCR): best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) measured by RECIST v1.1 criteria [ Time Frame: Baseline, week 12, 24, 36, 48, 60, 72 and early withdrawal visit (may occur at anytime post treatment up to 72 weeks) ]
  • Change in Quality of Life (QoL), as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 [ Time Frame: Baseline, week 12, 24, 36, 48, 60, 72, early withdrawal visit (may occur at anytime post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Change in Patient satisfaction of disease management, as assessed by the Treatment Satisfaction Questionnaire for Medication-9 scale (TSQM-9 scale) [ Time Frame: Baseline, week 12, 24, 36, 48, 60, 72, early withdrawal visit (may occur at anytime post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Time to QoL deterioration, defined by a decrease from baseline in EORTC Quality of Life Questionnaire C30 (QLQ-C30) score of at least 10 points [ Time Frame: Baseline, week 12, 24, 36, 48, 60, 72, early withdrawal visit (may occur at anytime post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Objective Response Rate (ORR): best overall response of CR or PR measured by RECIST v1.1 criteria [ Time Frame: Baseline, week 12, 24, 36, 48, 60, 72, early withdrawal visit (may occur at anytime post treatment up to 72 weeks) ]
  • Mean changes from Baseline in urinary 5-HIAA levels in subjects with elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) (≥2 x Upper limit of normal range) at Baseline [ Time Frame: Baseline, week 8, 12, 24, 36, 48, 60, 72 and early withdrawal visit (may occur at anytime post treatment up to 72 weeks) and then every 12 weeks up to 18 months (approximately) after the last patient is randomised (175 progression/death events)] ]
  • Overall Survival, defined as the time from randomization to death from any causes [ Time Frame: From randomisation up to 18 months (approximately) after the last patient is randomised] ]
    The analysis will occur when the target number of events (175 progression/death events) among the two treatment groups has been observed.
  • Plasma Concentration of lanreotide in serum [ Time Frame: Baseline, week 24, week 36, early withdrawal visit (may occur at anytime post treatment up to 72 weeks) ]
    Pharmacokinetics (PK) of LAN
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumors
Official Title  ICMJE A Phase 3, Prospective, Randomized, Double-blind, Multi-center Study of the Efficacy and Safety of Lanreotide Autogel/Depot 120 mg Plus BSC vs. Placebo Plus BSC for Tumor Control in Subjects With Well Differentiated, Metastatic and/or Unresectable, Typical or Atypical, Lung Neuroendocrine Tumors
Brief Summary

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 lung NETs This study contains two phases: the Double-Blind (DB) Phase, and the Open Label (OL) Extension Phase. The DB Phase includes: Screening, Baseline and Treatment period. The OL Extension Phase will consist of two periods: Treatment Period and Follow-Up Period.

The primary objective will be to compare the antitumour efficacy of Lanreotide Autogel/Depot 120 mg (LAN) plus Best Supportive Care (BSC) every 28 days versus placebo plus BSC, 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 with unresectable and/or metastatic well differentiated, typical or atypical lung neuroendocrine tumours

Detailed Description

The DB Phase will include a Screening Visit to establish protocol eligibility and disease characteristics. The Baseline Visit will confirm eligibility prior to randomization and treatment. The DB Phase of the study will end on the date of data cut-off for the primary analysis of PFS, which will occur when the target number of events (175 disease Progression as centrally assessed or deaths reached) between the two treatment groups has been observed.

All subjects who are still on study treatment at that time will enter the OL Extension Phase (either the Treatment Period or Follow-Up Period). In the OL Extension Treatment Period, the subjects will be allowed to receive active treatment if they were randomized in the placebo arm. During the OL Follow-up Period, all subjects will continue to be followed for QoL survival and all subsequent anticancer treatments received will be recorded.

Both OL Extension Treatment Period and Follow-up Phases will end 6 months after the date of data cut-off (175 events - progression as assessed centrally or death - are reached).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Neuroendocrine Tumors
Intervention  ICMJE
  • Drug: Lanreotide (Autogel formulation)
    120mg every 28 days until disease progression
    Other Names:
    • Lanreotide Depot
    • Somatuline
  • Drug: Placebo
    Saline solution 0.9% administered via deep subcutaneous injection every 28 days until disease progression.
Study Arms  ICMJE
  • Experimental: Lanreotide (Autogel formulation)
    120mg every 28 days until disease progression
    Intervention: Drug: Lanreotide (Autogel formulation)
  • Placebo Comparator: Placebo
    120mg every 28 days until disease progression, then patient may enter open-label treatment with Lanreotide
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 1, 2019)
77
Original Estimated Enrollment  ICMJE
 (submitted: February 16, 2016)
216
Estimated Study Completion Date  ICMJE February 2020
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have metastatic and/or unresectable pathologically confirmed well-differentiated, typical or atypical neuroendocrine tumor of the lung
  • Histologic evidence of Well differentiated Neuroendocrine tumors (NETs) of the lung (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 lung origin are excluded
  • Has been treated with an Somatostatin analogs (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 Lung NET
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   Denmark,   France,   Germany,   Italy,   Netherlands,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02683941
Other Study ID Numbers  ICMJE A-US-52030-328
2015-004992-62 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ipsen
Study Sponsor  ICMJE Ipsen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ipsen Medical Director Ipsen
PRS Account Ipsen
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP