Clinical trial NCT00412061: Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoid Tumor
Malignant Carcinoid Syndrome
Keywords: Cancer
Carcinoid
Tumor
Neuroendocrine
Carcinoma
Everolimus
Octreotide
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-12-15
Enrollment: 429
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review
timeFrame: 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:
measure: Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: 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
measure: Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level
timeFrame: 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
measure: Overall Survival Using Kaplan-Meier Methodology
timeFrame: Months 12, 24, 36, 48
measure: Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase)
timeFrame: From first day of treatment up to 28 days after last day of treatment in double blind
measure: Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Open Label Phase)
timeFrame: From first day of treatment up to 28 days after last day of treatment in double blind
measure: Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline Chromogranin A (CgA)
timeFrame: 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
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona / Arizona Cancer Center Deptof Uof A/Arizona Cancer(2)
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group The Center for Chest Care
state: Arkansas
city: Little Rock
country: United States
facility: Hematology Oncology Services of Arkansas
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center SC-2
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA New SC Address
state: California
city: Aurora
country: United States
facility: University of Colorado Dept. of Univ. of Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers Dept of Rocky Mountain (2)
state: Colorado
city: Norwich
country: United States
facility: Eastern Connecticut Hematology & Oncology Associates Dept. of ECHO
state: Connecticut
city: Southington
country: United States
facility: Cancer Centers of Connecticut Southington Location
state: Connecticut
city: Stamford
country: United States
facility: Hematology Oncology PC Dept.of Hematology Oncology(2)
state: Connecticut
city: Ocala
country: United States
facility: Ocala Oncology Center Dept. of Ocala Oncology Center
state: Florida
city: Niles
country: United States
facility: Cancer Care and Hematology Specialists of Chicagoland Niles
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Dept.of IndianaUniv.CancerCtr
state: Indiana
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers CICC - South
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Medical Center Internal Medicine
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center Deptof Uof Kansas CancerCenter
state: Kansas
city: Overland Park
country: United States
facility: Kansas City Cancer Center KCCC Business Office
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute Clinical Research Program
state: Kentucky
city: New Orleans
country: United States
facility: LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Deptof LSU Health Sciences (2)
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic - Rochester Division of Hematology
state: Minnesota
city: St. Louis
country: United States
facility: Washington University School Of Medicine-Siteman Cancer Ctr Division of Oncology
state: Missouri
city: St. Louis
country: United States
facility: The Center for Cancer Care and Research
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center Medical Oncology
state: New Hampshire
city: Albany
country: United States
facility: New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
state: New York
city: New York
country: United States
facility: New York University Medical Center NYU Medical Center (2)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center Dept. of Duke Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas CC of C -Eastside
state: South Carolina
city: Austin
country: United States
facility: Texas Oncology, P.A. Central Austin Cancer Center
state: Texas
city: Corpus Christi
country: United States
facility: South Texas Institute of Cancer S. Tex Inst.- Corpus Christi
state: Texas
city: Dallas
country: United States
facility: Sammons Cancer Center - Texas Oncology Sammons Cancer Center (SC)
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A. Forth Worth -- 12th Avenue
state: Texas
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates VOA - Lake Wright
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists Compass Oncology -BKM
state: Washington
city: Madison
country: United States
facility: University of Wisconsin / Paul P. Carbone Comp Cancer Center GI Oncology Research Center
state: Wisconsin
city: Kogarah
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Herston
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Praha 2
country: Czech Republic
facility: Novartis Investigative Site
city: Pribram
country: Czech Republic
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Clichy Cédex
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris Cedex 15
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Basingstoke
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Fazio 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.
citation: Pavel 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.