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.
Recent updates of NCCN & ENETS guidelines recommend SSA in first line for the treatment of
locoregional unresectable or metastatic lung NETs as an option beyond
'observation''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)
extension 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, lung NETs.
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 in Lung
Interventions
| Drug | Synonyms | Arms |
|---|
| Lanreotide (Autogel formulation) | Lanreotide Depot (US) | Lanreotide (Autogel formulation) |
| Placebo | | Placebo |
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.
Recent updates of NCCN & ENETS guidelines recommend SSA in first line for the treatment of
locoregional unresectable or metastatic lung NETs as an option beyond
'observation''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)
extension 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, lung NETs.
Detailed Description
As planned initially, a total of 216 eligible patients with well-differentiated typical or
atypical, metastatic and/or unresectable lung NETs, and a positive somatostatin receptor
imaging (SRI) (Octreoscan® ≥ grade 2 Krenning scale; Ga-PET scan: uptake greater than liver
background), had to be randomized 2:1 to either LAN plus BSC (120mg/28 days) or placebo plus
BSC following the stratification of 1) typical versus atypical and 2) prior chemotherapy
versus no prior chemotherapy*. At the time of the premature stop of the recruitment (as per
Protocol Amendment #5), 77 patients have been enrolled. All patients still treated in the DB
Phase have been entered into the OL Extension Phase (either for Follow up or for OL treatment
periods). The transition to the OL Extension periods was done on a country-basis and per
patient, at the following planned scheduled visit (i.e. approximately 28 days from the last
injection). Patients enrolled into the study not progressing at the time of transition, and
who agree to stay on LAN therapy (i.e. OL Treatment Period) not progressing at the time of
transition, and who agree to stay on LAN therapy (i.e. OL Treatment Period) will receive the
study active treatment until evidence of disease progression (based on local radiological
assessment then confirmed centrally), development of unacceptable toxicity, or premature
withdrawal for any reason or up a maximum of 18 months after the last patient randomized.
After disease progression patients are followed for survival, QoL and all subsequent
anticancer treatments in the OL Follow-up period up to the end of the study (i.e up to 18
months after the last patient randomized).
* cytotoxic chemotherapy or molecular targeted therapy or interferon.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Lanreotide (Autogel formulation) | Experimental | 120mg every 28 days until disease progression, death, or unacceptable toxicity | - Lanreotide (Autogel formulation)
|
| Placebo | Placebo Comparator | 120mg every 28 days until disease progression, death, or unacceptable toxicity then patient may enter open-label treatment with Lanreotide | |
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
- 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 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), for subjects randomized in LAN group, assessed by central review using RECIST v1.1 criteria |
| Time Frame: | From randomization up to disease progression or up to 18 months (approximately) after the last patient is randomized either in the DB period or in the OL period. . |
| 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: | Progression-free survival (PFS), assessed by central review using RECIST v1.1 criteria every 12 weeks, |
| Time Frame: | From randomization to disease progression or death from any causes during the double-blind phase |
| Safety Issue: | |
| Description: | |
| Measure: | Progression-free survival (PFS), assessed by local review using RECIST v1.1 criteria every 12 weeks |
| Time Frame: | From randomization to disease progression or death from any causes during the double-blind phase |
| Safety Issue: | |
| Description: | |
| Measure: | ORR: objective response rate measured by RECIST v1.1 criteria every 12 weeks |
| Time Frame: | From randomisation up to the Post Treatment/Early Withdrawal Visit during the double-blind phase |
| Safety Issue: | |
| Description: | |
| Measure: | Time to treatment failure during the double-blind phase |
| Time Frame: | From randomisation up to event according to central review or to event according to local review whatever the one which occurs first |
| Safety Issue: | |
| Description: | Defined as the time from randomization to disease progression using RECIST v1.1, death, consent withdrawn, an AE, 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 LAR SSA), or initiation of anticancer treatment |
| Measure: | Mean changes from Baseline in the biomarker chromogranin A (CgA) |
| Time Frame: | Every 12 weeks thereafter until the post Double-Blind and in the Open Label Extension Treatment Phase |
| 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: | Double-blind and the Open-label treatment phases |
| 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, every 12 weeks and at the Post treatment/Early Withdrawal Visit and in the OL Extension Treatment and Follow-up phases |
| 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: | Double-blind, Open-label Treatment and Follow-up phases |
| 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: | Every 12 weeks thereafter, and at the Post Treatment/Early Withdrawal Visit and in the Open-label Extension Treatment phase |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Ipsen |
Last Updated
March 2, 2021
