Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00412061
First received: December 13, 2006
Last updated: November 11, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Carcinoid Tumor
Malignant Carcinoid Syndrome
Drug: Octreotide
Drug: Placebo
Drug: Everolimus
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Overall Survival Using Kaplan-Meier Methodology [ Time Frame: Months 12, 24, 36, 48 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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".


Enrollment: 429
Study Start Date: December 2006
Study Completion Date: June 2013
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Sandostatin LAR® Depot
Drug: Everolimus
A 10-mg oral daily dosing regimen (two 5-mg tablets) of everolimus.
Other Name: 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 Name: Sandostatin LAR® Depot
Drug: Placebo
A 10-mg oral daily dosing regimen (two 5-mg tablets) of matching placebo.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00412061

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

Additional Information:
No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00412061     History of Changes
Other Study ID Numbers: CRAD001C2325, 2006-004507-18
Study First Received: December 13, 2006
Results First Received: October 25, 2011
Last Updated: November 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Cancer
Carcinoid
Tumor
Neuroendocrine
Carcinoma
Everolimus
Octreotide

Additional relevant MeSH terms:
Carcinoid Tumor
Malignant Carcinoid Syndrome
Neoplasms
Serotonin Syndrome
Adenocarcinoma
Carcinoma
Chemically-Induced Disorders
Drug-Related Side Effects and Adverse Reactions
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Everolimus
Octreotide
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014