Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor

Carcinoid Tumor Clinical Trial

— RADIANT-2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00412061
• Other study ID #: CRAD001C2325
• Secondary ID: 2006-004507-18
• Status: Completed
• Phase: Phase 3
• First received: December 13, 2006
• Last updated: November 11, 2014
• Start date: December 2006
• Est. completion date: June 2013

Study information

• Verified date: November 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 429
• Est. completion date: June 2013
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Carcinoid Tumor
• Malignant Carcinoid Syndrome
• Neuroendocrine Tumors
• Serotonin Syndrome

Intervention

Drug:
• Octreotide
Octreotide 30 mg intramuscularly (i.m.) every 28 days.
• Placebo
A 10-mg oral daily dosing regimen (two 5-mg tablets) of matching placebo.
• Everolimus
A 10-mg oral daily dosing regimen (two 5-mg tablets) of everolimus.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Herston	Queensland
Australia	Novartis Investigative Site	Kogarah	New South Wales
Australia	Novartis Investigative Site	South Brisbane	Queensland
Belgium	Novartis Investigative Site	Bruxelles
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Czech Republic	Novartis Investigative Site	Praha 2
Czech Republic	Novartis Investigative Site	Pribram
Finland	Novartis Investigative Site	Helsinki
France	Novartis Investigative Site	Clichy Cédex
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Paris Cedex 15
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Toulouse Cedex 9
France	Novartis Investigative Site	Villejuif Cedex
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Hamburg
Greece	Novartis Investigative Site	Athens
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Perugia	PG
Italy	Novartis Investigative Site	Pisa	PI
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Slovakia	Novartis Investigative Site	Bratislava	Slovak Republic
Spain	Novartis Investigative Site	Madrid
Sweden	Novartis Investigative Site	Uppsala
United Kingdom	Novartis Investigative Site	Basingstoke
United States	New York Oncology Hematology, P.C. Dept. of New York Oncology. PC	Albany	New York
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	University of Colorado Dept. of Univ. of Colorado	Aurora	Colorado
United States	Texas Oncology, P.A. Central Austin Cancer Center	Austin	Texas
United States	South Texas Institute of Cancer S. Tex Inst.- Corpus Christi	Corpus Christi	Texas
United States	Sammons Cancer Center - Texas Oncology Sammons Cancer Center (SC)	Dallas	Texas
United States	Rocky Mountain Cancer Centers Dept of Rocky Mountain (2)	Denver	Colorado
United States	Duke University Medical Center Dept. of Duke Cancer Center	Durham	North Carolina
United States	Highlands Oncology Group The Center for Chest Care	Fayetteville	Arkansas
United States	Texas Oncology, P.A. Forth Worth -- 12th Avenue	Fort Worth	Texas
United States	Cancer Centers of the Carolinas CC of C -Eastside	Greenville	South Carolina
United States	University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology	Houston	Texas
United States	Central Indiana Cancer Centers CICC - South	Indianapolis	Indiana
United States	Indiana University Dept.of IndianaUniv.CancerCtr	Indianapolis	Indiana
United States	University of Iowa Medical Center Internal Medicine	Iowa City	Iowa
United States	University of Kansas Cancer Center Deptof Uof Kansas CancerCenter	Kansas City	Kansas
United States	Dartmouth Hitchcock Medical Center Medical Oncology	Lebanon	New Hampshire
United States	Hematology Oncology Services of Arkansas	Little Rock	Arkansas
United States	Cedars Sinai Medical Center SC-2	Los Angeles	California
United States	University of California at Los Angeles UCLA New SC Address	Los Angeles	California
United States	Norton Cancer Institute Clinical Research Program	Louisville	Kentucky
United States	University of Wisconsin / Paul P. Carbone Comp Cancer Center GI Oncology Research Center	Madison	Wisconsin
United States	LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Deptof LSU Health Sciences (2)	New Orleans	Louisiana
United States	New York University Medical Center NYU Medical Center (2)	New York	New York
United States	Cancer Care and Hematology Specialists of Chicagoland Niles	Niles	Illinois
United States	Virginia Oncology Associates VOA - Lake Wright	Norfolk	Virginia
United States	Eastern Connecticut Hematology & Oncology Associates Dept. of ECHO	Norwich	Connecticut
United States	Ocala Oncology Center Dept. of Ocala Oncology Center	Ocala	Florida
United States	Kansas City Cancer Center KCCC Business Office	Overland Park	Kansas
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic - Rochester Division of Hematology	Rochester	Minnesota
United States	Cancer Centers of Connecticut Southington Location	Southington	Connecticut
United States	The Center for Cancer Care and Research	St. Louis	Missouri
United States	Washington University School Of Medicine-Siteman Cancer Ctr Division of Oncology	St. Louis	Missouri
United States	Hematology Oncology PC Dept.of Hematology Oncology(2)	Stamford	Connecticut
United States	University of Arizona / Arizona Cancer Center Deptof Uof A/Arizona Cancer(2)	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists Compass Oncology -BKM	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)	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	No
Secondary	Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level	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	No
Secondary	Overall Survival Using Kaplan-Meier Methodology	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	No
Secondary	Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase)	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	Yes
Secondary	Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Open Label Phase)	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	Yes
Secondary	Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline Chromogranin A (CgA)	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	No

External Links

•   Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.