Clinical Trials /

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

NCT02683941

Description:

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

Related Conditions:
  • Lung Neuroendocrine Neoplasm
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: A-US-52030-328
  • SECONDARY ID: 2015-004992-62
  • NCT ID: NCT02683941

Conditions

  • Neuroendocrine Tumors

Interventions

DrugSynonymsArms
Lanreotide (Autogel formulation)Lanreotide Depot, SomatulineLanreotide (Autogel formulation)
PlaceboPlacebo

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Lanreotide (Autogel formulation)Experimental120mg every 28 days until disease progression
  • Lanreotide (Autogel formulation)
PlaceboPlacebo Comparator120mg every 28 days until disease progression, then patient may enter open-label treatment with Lanreotide
  • Placebo

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)]
Safety Issue:
Description: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

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:The analysis will occur when the target number of events (175 progression/death events) among the two treatment groups has been observed.
Measure: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)]
Safety Issue:
Description:The analysis will occur when the target number of events (175 progression/death events) among the two treatment groups has been observed.
Measure: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)]
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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)]
Safety Issue:
Description:
Measure: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)]
Safety Issue:
Description:
Measure: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)]
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:Pharmacokinetics (PK) of LAN

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ipsen

Last Updated

February 26, 2018