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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor

Short name RADIANT-2

NCTNCT00412061 (opens ClinicalTrials.gov in a new tab)Other idCRAD001C2325Other id2006-004507-18
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
429 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Randomized · Double masking
Countries
15 countries

United States, Australia, Belgium, Canada, Czechia, Finland, France, Germany, Greece, Italy, Netherlands, Slovakia, Spain, Sweden, United Kingdom

Start
Dec 2006
Primary completion
Apr 2010
Completion
Jun 2013
First posted
15 Dec 2006 (estimated)
Last update posted
21 Nov 2014 (estimated)
Conditions
Carcinoid Tumor · Malignant Carcinoid Syndrome

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20062008201020122014
  1. Ph 3

    RADIANT-2

    NCT00412061

    Dec 2006 to Jun 2013

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study was to evaluate whether everolimus 10 mg / day added to treatment with depot octreotide prolongs progression free survival compared to treatment with octreotide alone in patients with advanced carcinoid tumor.

Interventions

  • OctreotideDrug
  • PlaceboDrug
  • EverolimusDrug

Arms2

  • Experimental

    Octreotide+ Everolimus

    Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.

  • Placebo comparator

    Octreotide+ Placebo

    Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review

    Time frame · Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

    Registry description

    Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The primary analysis of PFS was based on the independent central adjudicated assessment using Kaplan-Meier method.

Secondary outcomes(6)

  1. Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)

    Time frame · Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

    Registry description

    The best overall response rate is defined as the percentage of patients having achieved confirmed Complete Response + Partial Response. Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. • Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression.

  2. Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level

    Time frame · If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

    Registry description

    5-HIAA levels in urine are frequently elevated in patients with advanced carcinoid tumors. Baseline levels of 5-HIAA in urine were defined as 'High' if they exceeded the median value, and 'Low' if they were lower than or equal to the median.

  3. Overall Survival Using Kaplan-Meier Methodology

    Time frame · Months 12, 24, 36, 48

    Registry description

    Overall survival was defined as the time from the date of randomization to the date of death from any cause. If a patient was not known to have died, survival was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the median overall survival for each treatment group.

  4. Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase)

    Time frame · From first day of treatment up to 28 days after last day of treatment in double blind

    Registry description

    AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

  5. Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Open Label Phase)

    Time frame · From first day of treatment up to 28 days after last day of treatment in double blind

    Registry description

    AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

  6. Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline Chromogranin A (CgA)

    Time frame · If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

    Registry description

    Serum CgA levels in urine are frequently elevated in patients with advanced carcinoid tumors. Baseline levels of serum CgA were characterized relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated".

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMedian· Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review

GroupValue (Months)
Octreotide+ Everolimus16.43
Octreotide+ Placebo11.33
Secondary and other outcome results(6)
Secondary outcomeNumber· Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)

GroupValue (Percentage of patients)
Octreotide+ Everolimus2.3
Octreotide+ Placebo1.9
Secondary outcomeMedian· If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level

GroupValue (Months)
Octreotide+ Everolimus21.75
Octreotide+ Placebo13.90
Secondary outcomeNumber· Months 12, 24, 36, 48

Overall Survival Using Kaplan-Meier Methodology

GroupValue (Percentage of Participants)
Octreotide+ Everolimus80.5
Octreotide+ Placebo Followed by Open Label Arm81.8
Secondary outcomeNumber· From first day of treatment up to 28 days after last day of treatment in double blind

Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase)

GroupValue (Patients)
Octreotide+ Everolimus208
Octreotide+ Placebo146
Secondary outcomeNumber· From first day of treatment up to 28 days after last day of treatment in double blind

Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Open Label Phase)

GroupValue (Patients)
Everolimus Open Label Arm154
Secondary outcomeMedian· If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline Chromogranin A (CgA)

GroupValue (Months)
Octreotide+ Everolimus31.31
Octreotide+ Placebo20.07

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Everolimus + OctreotideEverolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.–126 / 215214 / 215
Placebo + OctreotideMatching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.–74 / 211194 / 211
Everolimus Open LabelOpen Label - Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.–93 / 170162 / 170

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

0 studies on this page

Indexing hint: Randomized controlled trial · 2013

Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study.

Fazio et al. 2013Chestcited by 95

PMID 23187897DOI 10.1378/chest.12-1108PUB-23187897

Full text at the publisher
Publisher page

Indexing hint: Randomized controlled trial · 2011

Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study.

Pavel et al. 2011Lancet (London, England)cited by 732

PMID 22119496DOI 10.1016/s0140-6736(11)61742-xPUB-22119496

Full text at the publisher
Publisher page

More studies

1 study on this page

Indexing hint: Randomized controlled trial · 2017

Corrected

Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study.

Pavel et al. 2017Annals of oncology : official journal of the European Society for Medical Oncologycited by 81

PMID 28444114PMC7360141DOI 10.1093/annonc/mdx193PUB-28444114

Rights unknown
Source linkRead the notice

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria: * Advanced (unresectable or metastatic) carcinoid tumor * Confirmed low-grade or intermediate-grade neuroendocrine carcinoma * Documented progression of disease within 12 months prior to randomization. * Measurable disease determined by triphasic computer tomography (CT) scan or magnetic resonance imaging (MRI). Exclusion criteria: * Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoma, or small cell carcinoma. * Hepatic artery embolization within the last 6 months or cryoablation of hepatic metastasis within 2 months of enrollment. * Previous treatment with mammalian target of rapamycin (mTOR) inhibitors (sirolimus, temsirolimus, everolimus) * Intolerance or hypersensitivity to octreotide, everolimus, or other rapamycins. * Severe or uncontrolled medical conditions * Chronic treatment with corticosteroids or other immunosuppressive agent. * Other primary cancer within 3 years. Other protocol-defined inclusion/exclusion criteria applied

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