3-arm Trial to Evaluate Pasireotide LAR/Everolimus Alone/in Combination in Patients With Lung/Thymus NET - LUNA Trial (LUNA)

• ClinicalTrials.gov Identifier: NCT01563354
• Recruitment Status: Completed
• First Posted: March 27, 2012
• Results First Posted: April 2, 2021
• Last Update Posted: April 2, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: March 20, 2012
• First Posted Date: March 27, 2012
• Results First Submitted Date: February 4, 2021
• Results First Posted Date: April 2, 2021
• Last Update Posted Date: April 2, 2021
• Actual Study Start Date: August 16, 2013
• Actual Primary Completion Date: February 10, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2021)

Percentage of Participants Progression-free at 9 Months Based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) [ Time Frame: Baseline up to 9 months ]

Patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at Month 9 were to be considered as "progression-free" based on RECIST v1.1. Patients with missing tumor assessment, or with overall lesion response "unknown" at Month 9 were considered as "non progression-free", unless any of the following assessments at Week 48 or Week 52 indicate CR, PR, or SD, in which case the patient was to be considered as progression-free at Month 9. Patients discontinuing the study for any reason prior to the 9 month assessment were to be considered as "non progression-free".

• Original Primary Outcome Measures (submitted: March 26, 2012): Proportion of patients progression-free at 12 months [ Time Frame: 12 months ]

Current Secondary Outcome Measures (submitted: March 8, 2021)

• Summary of Progression-free Survival (PFS) Based on RECIST v1.1 [ Time Frame: Baseline, every 3 months up to 69 months ]
  Time from first study drug administration to objective tumor progression or death from any cause according to RECIST v1.1
• Kaplan-Meier Estimates of Progression-free Survival (PFS) [ Time Frame: Baseline, every 3 months up to 69 months ]
  Percent (%) event-free probability estimate is the estimated probability that a patient will remain event-free up to the specified time point. Percent event-free probability estimates are obtained from the Kaplan-Meier survival estimates. Events are time from first study drug administration to objective tumor progression or death from any cause according to RECIST v1.1.
• Summary of Time to Response (Months) [ Time Frame: Every 3 months up to Year 1 ]
  Time from start of treatment to the first observed objective tumor response (partial response or complete response) observed according to RECIST v1.1.
• Summary of Duration of Response (Months) [ Time Frame: Every 3 months up to Year 1 ]
  Date of first objective tumor response to date of tumor progression or death due to any cause.
• 12-month Disease Control Rate (DCR) and Objective Response Rate (ORR) [ Time Frame: Baseline up to Month 12 ]
  Objective response rate (ORR) was defined as the percentage of patients showing a best overall response (BOR) of CR or PR during the core study according to RECIST v1.1 criteria. The best overall response is interpreted as the best response recorded from the start of the treatment until disease progression/recurrence, death from any cause or until the patient withdraws consent, whichever is earliest. DCR was was defined as the percentage of participants with a best overall response of complete response, partial response or stable disease during 12 months of treatment according to RECIST v1.1.
• Biochemical Response Rate (BRR) for Chromogranin A (CgA) Levels [ Time Frame: Baseline up to Week 52 ]
  Percentage of patients showing normalization or a decrease of ≥ 30% of serum CgA concentrations compared to baseline.
• Duration of Biochemical Response (DBR), by Treatment (Full Analysis Set) [ Time Frame: Baseline up to Month 18 ]
  Time from the first documentation of biochemical response to the first documentation of biochemical progression or to death due to any cause, whichever occurred first. Biochemical progression is defined as an increase of serum CgA levels ≥ 25% compared to baseline.
• Kaplan-Meier Event-free Probability Estimate Based on CgA Levels [ Time Frame: Baseline, every 3 months up to Month 18 ]
  Kaplan Meier estimates are for Duration of biochemical response (DBR) outcome measure. Events are biochemical progressions i.e. an increase of CgA levels >= 25% compared to baseline or deaths due to any cause. Percent (%) Event-free probability estimate is the estimated probability that a patient will remain event-free up to the specified time point.
• Summary of Biochemical Progression-free Survival Based on CgA Levels by Treatment [ Time Frame: Baseline up Month 24 ]
  Time from the first documentation of biochemical response to the first documentation of biochemical progression or to death due to any cause, whichever occurred first. Biochemical progression is defined as an increase of serum CgA levels ≥ 25% compared to baseline.
• Kaplan-Meier Event-free Probability Estimate for Biochemical Progression-free Survival Based on CgA Levels [ Time Frame: Baseline, every 3 months up to Month 24 ]
  Percent (%) Event-free probability estimate is the estimated probability that a patient will remain event-free up to the specified time point. Percent event-free probability estimates are obtained from the Kaplan-Meier survival estimates. Events are biochemical progressions, i.e., an increase of CgA levels >= 25% compared to baseline or deaths due to any cause.
• Biochemical Response Rate (BRR) for 5HIAA Levels [ Time Frame: Baseline up Week 52 ]
  The percentages are the biochemical response rates i.e. percentage of patients showing normalization i.e. return to within normal ranges, or a decrease of >= 50% from baseline of 5HIAA concentrations.

Original Secondary Outcome Measures (submitted: March 26, 2012)

• Progression-free survival [ Time Frame: Every 3 months up to Year 1 ]
  Time from first study drug administration to objective tumor progression or death from any cause
• Disease control rate [ Time Frame: Every 3 months up to Year 1 ]
  Proportion of patients showing a best overall response of complete response, partial response or stable disease during 12 months of treatment
• Time to response [ Time Frame: Every 3 months up to Year 1 ]
  Time from start of treatment to the first observed objective tumor response (partial response or complete response)
• Duration of response [ Time Frame: Every 3 months up to Year 1 ]
  Time from onset of the first objective tumor response (partial response or complete response) to objective tumor progression or death from any cause
• Time to progression [ Time Frame: Every 3 months up to Year 1 ]
  Time from date of start of treatment to date of event defined as the first documented progression or death due to underling disease.
• Biochemical response rate [ Time Frame: Every 3 months up to Year 1 ]
  Percentage of patients showing normalization or a decrease > or = 50% of serum CgA, urinary 5HIAA
• Rate and severity of adverse events [ Time Frame: Week 2, 3 and 4; every month up to Year 3 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neuroendocrine Carcinoma of the Lung and Thymus

Intervention

• Drug: Pasireotide LAR
  60 mg was administered as an intra muscular depot injection once every 28 days starting at Day 1
  Other Name: SOM230
• Drug: Everolimus
  10 mg tables administered orally once a day
  Other Name: RAD001
• Drug: Pasireotide LAR and Everolimus Combination
  Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily
  Other Name: SOM230 + RAD001

Study Arms

• Experimental: Pasireotide LAR
  Pasireotide long acting release (LAR) 60 mg will be administered as an intra muscular (i.m.) depot injection once every 28 days starting on Day 1
  Intervention: Drug: Pasireotide LAR
• Experimental: Everolimus
  Everolimus 10 mg taken orally (p.o) once daily starting on Day 1
  Intervention: Drug: Everolimus
• Experimental: Pasireotide LAR and Everolimus Combination
  Pasireotide LAR 60 mg i.m. injected once every 28 days + Everolimus 10 mg p.o. daily starting on Day 1
  Intervention: Drug: Pasireotide LAR and Everolimus Combination

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 1, 2018): 124
• Original Estimated Enrollment (submitted: March 26, 2012): 112
• Actual Study Completion Date: February 10, 2020
• Actual Primary Completion Date: February 10, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, France, Germany, Greece, Italy, Netherlands, Spain, Sweden, United Kingdom
• Removed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT01563354
• Other Study ID Numbers: CSOM230DIC03; 2011-002872-17 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on

https://www.clinicalstudydatarequest.com/

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: March 2021