Clinical trial NCT01563354: 3-arm Trial to Evaluate Pasireotide LAR/Everolimus Alone/in Combination in Patients With Lung/Thymus NET - LUNA Trial
Official title: Multicenter 3-arm Trial to Evaluate the Efficacy and Safety of Pasireotide LAR or Everolimus Alone or in Combination in Patients With Well Differentiated Neuroendocrine Carcinoma of the Lung and Thymus - LUNA Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Carcinoma of the Lung and Thymus
Keywords: neuroendocrine carcinoma; lung; thymus; pasireotide LAR; everolimus,adult,SOM230,carcinoma,lung cancer,
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-03-27
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a multicenter, randomized, phase II study evaluating Everolimus or Pasireotide LAR alone or in combination in adult patients with advanced (unresectable or metastatic) neuroendocrine carcinoma of the lung and thymus

Detailed description: This was a prospective, multicenter, randomized, open-label, 3-arm, phase II study with a single-stage design in each arm. The purpose of this study was to test the effectiveness and safety of Everolimus or Pasireotide LAR alone or in combination in adult patients with advanced (unresectable or metastatic) neuroendocrine carcinoma (typical and atypical) of the lung and thymus. It was expected that a total of 120 patients with 40 patients in each arm were to be enrolled into this study. Patients were seen weekly for one month and monthly thereafter. Radiological and biochemical response assessments were performed every 3 months.

Patients with disease control (stable disease or better) in the combination arm or monotherapy with pasireotide LAR and everolimus who had not experienced unacceptable toxicity were permitted to continue treatment in the extension phase of the study and were seen every 3 months. Patients could remain in the extension phase as long as they continued to have clinical benefit and had not fulfilled any of the study discontinuation criteria. All patients had a safety follow-up visit 56 days after last treatment dose.

Eligibility criteria: Inclusion Criteria:

* Histological confirmed advanced well differentiated typical and atypical carcinoid tumors of the lung or thymus
* Patients of all treatment lines including naive patients could have been enrolled
* At least one measurable lesion of disease on CT scan or MRI
* Radiological documentation of disease progression within 12 months prior to randomization
* Adequate liver, renal and bone marrow function
* WHO Performance Status 0-2

Exclusion Criteria:

* Poorly differentiated neuroendocrine carcinoma
* Non-neuroendocrine thymoma
* Patients with severe functional disease who required symptomatic treatment with somatostatin analogs
* Prior therapy with mTOR inhibitors
* History of liver disease
* Baseline QTcF\> 470 msec
* Uncontrolled diabetes mellitus despite adequate therapy

Primary outcomes:
measure: Percentage of Participants Progression-free at 9 Months Based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
timeFrame: Baseline up to 9 months
Secondary outcomes:
measure: Summary of Progression-free Survival (PFS) Based on RECIST v1.1
timeFrame: Baseline, every 3 months up to 69 months
measure: Kaplan-Meier Estimates of Progression-free Survival (PFS)
timeFrame: Baseline, every 3 months up to 69 months
measure: Summary of Time to Response (Months)
timeFrame: Every 3 months up to Year 1
measure: Summary of Duration of Response (Months)
timeFrame: Every 3 months up to Year 1
measure: 12-month Disease Control Rate (DCR) and Objective Response Rate (ORR)
timeFrame: Baseline up to Month 12
measure: Biochemical Response Rate (BRR) for Chromogranin A (CgA) Levels
timeFrame: Baseline up to Week 52
measure: Duration of Biochemical Response (DBR), by Treatment (Full Analysis Set)
timeFrame: Baseline up to Month 18
measure: Kaplan-Meier Event-free Probability Estimate Based on CgA Levels
timeFrame: Baseline, every 3 months up to Month 18
measure: Summary of Biochemical Progression-free Survival Based on CgA Levels by Treatment
timeFrame: Baseline up Month 24
measure: Kaplan-Meier Event-free Probability Estimate for Biochemical Progression-free Survival Based on CgA Levels
timeFrame: Baseline, every 3 months up to Month 24
measure: Biochemical Response Rate (BRR) for 5HIAA Levels
timeFrame: Baseline up Week 52
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen N
country: Denmark
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
state: Cedex 9
city: Creteil
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Rennes
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Bad Berka
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Viagrande
country: Italy
facility: Novartis Investigative Site
state: CT
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Orbassano
country: Italy
facility: Novartis Investigative Site
state: TO
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Withington
country: United Kingdom
facility: Novartis Investigative Site
state: Greater Manchester
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Ferolla P, Brizzi MP, Meyer T, Mansoor W, Mazieres J, Do Cao C, Lena H, Berruti A, Damiano V, Buikhuisen W, Gronbaek H, Lombard-Bohas C, Grohe C, Minotti V, Tiseo M, De Castro J, Reed N, Gislimberti G, Singh N, Stankovic M, Oberg K, Baudin E. Efficacy and safety of long-acting pasireotide or everolimus alone or in combination in patients with advanced carcinoids of the lung and thymus (LUNA): an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2017 Dec;18(12):1652-1664. doi: 10.1016/S1470-2045(17)30681-2. Epub 2017 Oct 23.