Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumors (SPINET)
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|ClinicalTrials.gov Identifier: NCT02683941|
Recruitment Status : Active, not recruiting
First Posted : February 17, 2016
Last Update Posted : October 1, 2019
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'. Consequently, it was decided to prematurely stop the recruitment in the SPINET study and to transition subjects still treated in the double-blind phase to the OL treatment phase following the country approval 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.
|Condition or disease||Intervention/treatment||Phase|
|Neuroendocrine Tumors in Lung||Drug: Lanreotide (Autogel formulation) Drug: Placebo||Phase 3|
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*. Due to 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 Treatment Period (either for follow up or for OL treatment). The transition to the OL treatment period was done by country and per patient, at the following planned scheduled visit (i.e. approximately 28 days from the last injection). Patients enrolled into the study stay on LAN therapy (i.e. OL Treatment Period) until evidence of disease progression (assessed locally and confirmed centrally), development of unacceptable toxicity, or premature withdrawal for any reason or up to 18 months after the last patient randomised. After disease progression patients are followed for survival, QoL and all subsequent anticancer treatments up to the end of the study.
* cytotoxic chemotherapy or molecular targeted therapy or interferon.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||77 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
|Actual Study Start Date :||February 2016|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||February 2020|
Experimental: Lanreotide (Autogel formulation)
120mg every 28 days until disease progression
Drug: Lanreotide (Autogel formulation)
120mg every 28 days until disease progression
Placebo Comparator: Placebo
120mg every 28 days until disease progression, then patient may enter open-label treatment with Lanreotide
Saline solution 0.9% administered via deep subcutaneous injection every 28 days until disease progression.
- Progression-Free Survival (PFS), for subjects randomized in LAN group, assessed by central review using RECIST v1.1 criteria [ Time Frame: From randomisation up to disease progression or up to 18 months (approximately) after the last patient is randomised. ]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
- 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 ]
- 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 ]
- ORR: objective response rate of CR or PR 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 ]
- 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 ]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
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02683941
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|Study Director:||Ipsen Medical Director||Ipsen|