Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor
RADIANT-2
A Randomized, Double-blind Placebo-controlled, Multicenter Phase III Study in Patients With Advanced Carcinoid Tumor Receiving Octreotide Depot and Everolimus 10 mg/Day or Octreotide Depot and Placebo
2 other identifiers
interventional
429
15 countries
70
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 2006
Longer than P75 for phase_3
70 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2006
CompletedFirst Submitted
Initial submission to the registry
December 13, 2006
CompletedFirst Posted
Study publicly available on registry
December 15, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2010
CompletedResults Posted
Study results publicly available
March 12, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2013
CompletedNovember 21, 2014
November 1, 2014
3.3 years
December 13, 2006
October 25, 2011
November 11, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review
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.
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
Secondary Outcomes (6)
Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)
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 Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level
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
Overall Survival Using Kaplan-Meier Methodology
Months 12, 24, 36, 48
Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase)
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)
From first day of treatment up to 28 days after last day of treatment in double blind
- +1 more secondary outcomes
Study Arms (2)
Octreotide+ Everolimus
EXPERIMENTALEverolimus 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.
Octreotide+ Placebo
PLACEBO COMPARATORMatching 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.
Interventions
Octreotide 30 mg intramuscularly (i.m.) every 28 days.
A 10-mg oral daily dosing regimen (two 5-mg tablets) of matching placebo.
A 10-mg oral daily dosing regimen (two 5-mg tablets) of everolimus.
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (70)
University of Arizona / Arizona Cancer Center Deptof Uof A/Arizona Cancer(2)
Tucson, Arizona, 85719, United States
Highlands Oncology Group The Center for Chest Care
Fayetteville, Arkansas, 72703, United States
Hematology Oncology Services of Arkansas
Little Rock, Arkansas, 72205, United States
Pacific Cancer Medical Center, Inc.
Anaheim, California, 92801, United States
Cedars Sinai Medical Center SC-2
Los Angeles, California, 90048, United States
University of California at Los Angeles UCLA New SC Address
Los Angeles, California, 90095, United States
University of Colorado Dept. of Univ. of Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Cancer Centers Dept of Rocky Mountain (2)
Denver, Colorado, 80218, United States
Eastern Connecticut Hematology & Oncology Associates Dept. of ECHO
Norwich, Connecticut, 06360, United States
Cancer Centers of Connecticut Southington Location
Southington, Connecticut, 06489, United States
Hematology Oncology PC Dept.of Hematology Oncology(2)
Stamford, Connecticut, 06902, United States
Ocala Oncology Center Dept. of Ocala Oncology Center
Ocala, Florida, 34471, United States
Cancer Care and Hematology Specialists of Chicagoland Niles
Niles, Illinois, 60714, United States
Indiana University Dept.of IndianaUniv.CancerCtr
Indianapolis, Indiana, 46202, United States
Central Indiana Cancer Centers CICC - South
Indianapolis, Indiana, 46227, United States
University of Iowa Medical Center Internal Medicine
Iowa City, Iowa, 52242, United States
University of Kansas Cancer Center Deptof Uof Kansas CancerCenter
Kansas City, Kansas, 66160, United States
Kansas City Cancer Center KCCC Business Office
Overland Park, Kansas, 66210, United States
Norton Cancer Institute Clinical Research Program
Louisville, Kentucky, 40202, United States
LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Deptof LSU Health Sciences (2)
New Orleans, Louisiana, 70112, United States
Mayo Clinic - Rochester Division of Hematology
Rochester, Minnesota, 55905, United States
Washington University School Of Medicine-Siteman Cancer Ctr Division of Oncology
St Louis, Missouri, 63110, United States
The Center for Cancer Care and Research
St Louis, Missouri, 63141, United States
Dartmouth Hitchcock Medical Center Medical Oncology
Lebanon, New Hampshire, 03756, United States
New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
Albany, New York, 12206, United States
New York University Medical Center NYU Medical Center (2)
New York, New York, 10016, United States
Duke University Medical Center Dept. of Duke Cancer Center
Durham, North Carolina, 27710, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497, United States
Cancer Centers of the Carolinas CC of C -Eastside
Greenville, South Carolina, 29615, United States
Texas Oncology, P.A. Central Austin Cancer Center
Austin, Texas, 78731, United States
South Texas Institute of Cancer S. Tex Inst.- Corpus Christi
Corpus Christi, Texas, 78405, United States
Sammons Cancer Center - Texas Oncology Sammons Cancer Center (SC)
Dallas, Texas, 75246, United States
Texas Oncology, P.A. Forth Worth -- 12th Avenue
Fort Worth, Texas, 76104, United States
University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
Houston, Texas, 77030, United States
Tyler Cancer Center
Tyler, Texas, 75702, United States
Virginia Oncology Associates VOA - Lake Wright
Norfolk, Virginia, 23502, United States
Northwest Cancer Specialists Compass Oncology -BKM
Vancouver, Washington, 98684, United States
University of Wisconsin / Paul P. Carbone Comp Cancer Center GI Oncology Research Center
Madison, Wisconsin, 53792, United States
Novartis Investigative Site
Kogarah, New South Wales, 2217, Australia
Novartis Investigative Site
Herston, Queensland, 4029, Australia
Novartis Investigative Site
South Brisbane, Queensland, 4101, Australia
Novartis Investigative Site
Brussels, 1070, Belgium
Novartis Investigative Site
London, Ontario, N6A 4L6, Canada
Novartis Investigative Site
Toronto, Ontario, M5G 2M9, Canada
Novartis Investigative Site
Montreal, Quebec, H1T 2M4, Canada
Novartis Investigative Site
Montreal, Quebec, H2X 1P1, Canada
Novartis Investigative Site
Prague, Czech Republic, 128 08, Czechia
Novartis Investigative Site
Příbram, 261 95, Czechia
Novartis Investigative Site
Helsinki, FIN-00290, Finland
Novartis Investigative Site
Strasbourg, France, 67098, France
Novartis Investigative Site
Clichy Cédex, 92118, France
Novartis Investigative Site
Lille, 59020, France
Novartis Investigative Site
Montpellier, 34298, France
Novartis Investigative Site
Paris, 75908, France
Novartis Investigative Site
Toulouse, 31059, France
Novartis Investigative Site
Villejuif, 94805, France
Novartis Investigative Site
Berlin, 13353, Germany
Novartis Investigative Site
Hamburg, 20246, Germany
Novartis Investigative Site
Athens, Greece, GR 11527, Greece
Novartis Investigative Site
Bologna, BO, 40138, Italy
Novartis Investigative Site
Milan, MI, 20100, Italy
Novartis Investigative Site
Milan, MI, 20141, Italy
Novartis Investigative Site
Perugia, PG, 06132, Italy
Novartis Investigative Site
Pisa, PI, 56126, Italy
Novartis Investigative Site
Groningen, 9713 GZ, Netherlands
Novartis Investigative Site
Rotterdam, 3015 CE, Netherlands
Novartis Investigative Site
Bratislava, Slovak Republic, 813 69, Slovakia
Novartis Investigative Site
Madrid, Madrid, 28041, Spain
Novartis Investigative Site
Uppsala, SE-751 85, Sweden
Novartis Investigative Site
Basingstoke, RG24 9NA, United Kingdom
Related Publications (3)
Pavel ME, Baudin E, Oberg KE, Hainsworth JD, Voi M, Rouyrre N, Peeters M, Gross DJ, Yao JC. 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. Ann Oncol. 2017 Jul 1;28(7):1569-1575. doi: 10.1093/annonc/mdx193.
PMID: 28444114DERIVEDFazio N, Granberg D, Grossman A, Saletan S, Klimovsky J, Panneerselvam A, Wolin EM. Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study. Chest. 2013 Apr;143(4):955-962. doi: 10.1378/chest.12-1108.
PMID: 23187897DERIVEDPavel ME, Hainsworth JD, Baudin E, Peeters M, Horsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. 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. Lancet. 2011 Dec 10;378(9808):2005-2012. doi: 10.1016/S0140-6736(11)61742-X. Epub 2011 Nov 25.
PMID: 22119496DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 13, 2006
First Posted
December 15, 2006
Study Start
December 1, 2006
Primary Completion
April 1, 2010
Study Completion
June 1, 2013
Last Updated
November 21, 2014
Results First Posted
March 12, 2012
Record last verified: 2014-11