Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor (RADIANT-2)

November 11, 2014 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

429

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Kogarah, New South Wales, Australia, 2217
        • Novartis Investigative Site
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Novartis Investigative Site
      • South Brisbane, Queensland, Australia, 4101
        • Novartis Investigative Site
  • Belgium
      • Bruxelles, Belgium, 1070
        • Novartis Investigative Site
  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H2X 1P1
        • Novartis Investigative Site
  • Czech Republic
      • Praha 2, Czech Republic, 128 08
        • Novartis Investigative Site
      • Pribram, Czech Republic, 261 95
        • Novartis Investigative Site
  • Finland
      • Helsinki, Finland, FIN-00290
        • Novartis Investigative Site
  • France
      • Clichy Cédex, France, 92118
        • Novartis Investigative Site
      • Lille Cedex, France, 59020
        • Novartis Investigative Site
      • Montpellier, France, 34298
        • Novartis Investigative Site
      • Paris Cedex 15, France, 75908
        • Novartis Investigative Site
      • Strasbourg, France, 67098
        • Novartis Investigative Site
      • Toulouse Cedex 9, France, 31059
        • Novartis Investigative Site
      • Villejuif Cedex, France, 94805
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 13353
        • Novartis Investigative Site
      • Hamburg, Germany, 20246
        • Novartis Investigative Site
  • Greece
      • Athens, Greece, GR 11527
        • Novartis Investigative Site
  • Italy
    • BO
      • Bologna, BO, Italy, 40138
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20141
        • Novartis Investigative Site
      • Milano, MI, Italy, 20100
        • Novartis Investigative Site
    • PG
      • Perugia, PG, Italy, 06132
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Italy, 56126
        • Novartis Investigative Site
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • Novartis Investigative Site
      • Rotterdam, Netherlands, 3015 CE
        • Novartis Investigative Site
  • Slovakia
    • Slovak Republic
      • Bratislava, Slovak Republic, Slovakia, 813 69
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28041
        • Novartis Investigative Site
  • Sweden
      • Uppsala, Sweden, SE-751 85
        • Novartis Investigative Site
  • United Kingdom
      • Basingstoke, United Kingdom, RG24 9NA
        • Novartis Investigative Site
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • University of Arizona / Arizona Cancer Center Deptof Uof A/Arizona Cancer(2)
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group The Center for Chest Care
      • Little Rock, Arkansas, United States, 72205
        • Hematology Oncology Services of Arkansas
    • California
      • Anaheim, California, United States, 92801
        • Pacific Cancer Medical Center, Inc.
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center SC-2
      • Los Angeles, California, United States, 90095
        • University of California at Los Angeles UCLA New SC Address
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Dept. of Univ. of Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers Dept of Rocky Mountain (2)
    • Connecticut
      • Norwich, Connecticut, United States, 06360
        • Eastern Connecticut Hematology & Oncology Associates Dept. of ECHO
      • Southington, Connecticut, United States, 06489
        • Cancer Centers of Connecticut Southington Location
      • Stamford, Connecticut, United States, 06902
        • Hematology Oncology PC Dept.of Hematology Oncology(2)
    • Florida
      • Ocala, Florida, United States, 34471
        • Ocala Oncology Center Dept. of Ocala Oncology Center
    • Illinois
      • Niles, Illinois, United States, 60714
        • Cancer Care and Hematology Specialists of Chicagoland Niles
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Dept.of IndianaUniv.CancerCtr
      • Indianapolis, Indiana, United States, 46227
        • Central Indiana Cancer Centers CICC - South
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Medical Center Internal Medicine
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center Deptof Uof Kansas CancerCenter
      • Overland Park, Kansas, United States, 66210
        • Kansas City Cancer Center KCCC Business Office
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute Clinical Research Program
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Deptof LSU Health Sciences (2)
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - Rochester Division of Hematology
    • Missouri
      • St. Louis, Missouri, United States, 63141
        • The Center for Cancer Care and Research
      • St. Louis, Missouri, United States, 63110
        • Washington University School Of Medicine-Siteman Cancer Ctr Division of Oncology
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center Medical Oncology
    • New York
      • Albany, New York, United States, 12206
        • New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
      • New York, New York, United States, 10016
        • New York University Medical Center NYU Medical Center (2)
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center Dept. of Duke Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center
    • South Carolina
      • Greenville, South Carolina, United States, 29615
        • Cancer Centers of the Carolinas CC of C -Eastside
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology, P.A. Central Austin Cancer Center
      • Corpus Christi, Texas, United States, 78405
        • South Texas Institute of Cancer S. Tex Inst.- Corpus Christi
      • Dallas, Texas, United States, 75246
        • Sammons Cancer Center - Texas Oncology Sammons Cancer Center (SC)
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology, P.A. Forth Worth -- 12th Avenue
      • Houston, Texas, United States, 77030
        • University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
      • Tyler, Texas, United States, 75702
        • Tyler Cancer Center
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates VOA - Lake Wright
    • Washington
      • Vancouver, Washington, United States, 98684
        • Northwest Cancer Specialists Compass Oncology -BKM
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin / Paul P. Carbone Comp Cancer Center GI Oncology Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Octreotide
Octreotide 30 mg intramuscularly (i.m.) every 28 days.
Other Names:
  • Sandostatin LAR® Depot
Drug: Everolimus
A 10-mg oral daily dosing regimen (two 5-mg tablets) of everolimus.
Other Names:
  • RAD001
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.
Drug: Octreotide
Octreotide 30 mg intramuscularly (i.m.) every 28 days.
Other Names:
  • Sandostatin LAR® Depot
Drug: Placebo
A 10-mg oral daily dosing regimen (two 5-mg tablets) of matching placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
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
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
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.
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
Time Frame: Months 12, 24, 36, 48
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.
Months 12, 24, 36, 48
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
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.
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)
Time Frame: From first day of treatment up to 28 days after last day of treatment in double blind
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.
From first day of treatment up to 28 days after last day of treatment in double blind
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
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".
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (ACTUAL)

April 1, 2010

Study Completion (ACTUAL)

June 1, 2013

Study Registration Dates

First Submitted

December 13, 2006

First Submitted That Met QC Criteria

December 14, 2006

First Posted (ESTIMATE)

December 15, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

November 21, 2014

Last Update Submitted That Met QC Criteria

November 11, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRAD001C2325
  • 2006-004507-18 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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