Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin)
NCT ID: NCT01524783
Last Updated: 2021-08-05
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
302 participants
INTERVENTIONAL
2012-03-30
2020-08-07
Brief Summary
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Detailed Description
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After assessment of eligibility, participants qualifying for the study were randomized in a 2:1 ratio to receive either everolimus or matching placebo. Participants received daily oral doses of 10 mg everolimus or matching placebo as study drug. In both arms, the study drug was combined with best supportive care and treatment cycles were defined as 28 days. Participants were treated until disease progression as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.0, intolerable toxicity, death, lost to follow-up or consent withdrawal. Regardless of the reason for study drug discontinuation, participants had a safety follow-up visit scheduled 30 days after the last dose of the study drug.
Per data monitoring committee recommendation, all participants on treatment with placebo were allowed to crossover to open-label treatment with everolimus. This change was implemented through protocol amendment 3 (issued on 06-May-2016) after which remaining participants entered into open-label phase of the study.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Everolimus + BSC
Participants received everolimus 10 mg once daily plus best supportive care (BSC) throughout the study
Everolimus
Participants were treated with everolimus 10 mg (two 5 mg tablets) once daily orally taken
Best suportive care (BSC)
Best supportive care includes all care provided to participants deemed necessary by the treating physician, such as but not restricted to anti-diarrheals and analgesics. The optimal care of the patient is based on the treating physician's best medical judgment.
Placebo + BSC
Participants received matching placebo once daily plus best supportive care (BSC) during the blinded period. Participants were allowed to crossover to treatment with everolimus 10mg once daily plus BSC during the open-label period.
Placebo
Participants were treated with two tablets of matching placebo once daily orally taken.
Best suportive care (BSC)
Best supportive care includes all care provided to participants deemed necessary by the treating physician, such as but not restricted to anti-diarrheals and analgesics. The optimal care of the patient is based on the treating physician's best medical judgment.
Interventions
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Everolimus
Participants were treated with everolimus 10 mg (two 5 mg tablets) once daily orally taken
Placebo
Participants were treated with two tablets of matching placebo once daily orally taken.
Best suportive care (BSC)
Best supportive care includes all care provided to participants deemed necessary by the treating physician, such as but not restricted to anti-diarrheals and analgesics. The optimal care of the patient is based on the treating physician's best medical judgment.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* No history of and no active symptoms related to carcinoid syndrome
* In addition to treatment-naive patients, patients previously treated with SSA, Interferon (IFN), one prior line of chemotherapy, and/or PRRT were allowed into the study. Pretreated patients had to have progressed on or after the last treatment
* Radiological documented disease progression within 6 months prior to randomization
* Measurable disease
* WHO performance status ≤1
* Adequate bone marrow, liver and renal function
Exclusion Criteria
* Patients with pancreatic NET or NET of origins other than GI or Lung
* Patients with history of or active symptoms of carcinoid syndrome (e.g. flushing, diarrhea)
* Patients with more than one line of prior chemotherapy
* Prior targeted therapy
* Hepatic intra-arterial embolization within the last 6 months. Cryoablation or radiofrequency ablation of hepatic metastases within 2 months of randomization
* Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus)
* Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
* Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
* Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy
* Patients who had any severe and/or uncontrolled medical conditions such as:
* unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to randomization, serious uncontrolled cardiac arrhythmia
* active or uncontrolled severe infection
* liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA)
* Chronic treatment with corticosteroids or other immunosuppressive agents
* Known history of HIV seropositivity
* Pregnant or nursing (lactating) women
18 Years
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
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University of California San Diego - Moores Cancer Center Regulatory
La Jolla, California, United States
Scripps Clinic Regulatory
La Jolla, California, United States
Cedars Sinai Medical Center SC
Los Angeles, California, United States
University of Colorado Cancer Centre SC
Aurora, Colorado, United States
H Lee Moffitt Cancer Center and Research Institute HLM
Tampa, Florida, United States
University of Chicago UC SC
Chicago, Illinois, United States
Goshen Center for Cancer Care IU Health SC
Indianapolis, Indiana, United States
Dana Farber Cancer Institute SC
Boston, Massachusetts, United States
Memorial Sloan Kettering MSkCC SC
New York, New York, United States
Montefiore Medical Center MMC
The Bronx, New York, United States
Oregon Health and Science University OH&SU
Portland, Oregon, United States
Vanderbilt University Medical Center Vanderbilt Med Ctr
Nashville, Tennessee, United States
Texas Oncology P A Texas Oncology Amarillo
Dallas, Texas, United States
Texas Oncology P A TX Oncology Baylor
Dallas, Texas, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
University of Texas MD Anderson Cancer Center UT MD Anderson Cancer Ctr
Houston, Texas, United States
University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc
Madison, Wisconsin, United States
Novartis Investigative Site
Innsbruck, Tyrol, Austria
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Vienna, , Austria
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Edegem, Antwerpen, Belgium
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Brussels, , Belgium
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Ghent, , Belgium
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Leuven, , Belgium
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Calgary, Alberta, Canada
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Vancouver, British Columbia, Canada
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Halifax, Nova Scotia, Canada
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London, Ontario, Canada
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Beijing, Beijing Municipality, China
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Beijing, , China
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Beijing, , China
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Beijing, , China
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Beijing, , China
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Bogotá, Cundinamarca, Colombia
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Brno, , Czechia
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Olomouc, , Czechia
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Prague, , Czechia
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Bad Berka, , Germany
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Berlin, , Germany
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Essen, , Germany
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Frankfurt, , Germany
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Hanover, , Germany
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Magdeburg, , Germany
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Mainz, , Germany
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Athens, , Greece
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Budapest, , Hungary
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Budapest, , Hungary
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Bologna, BO, Italy
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Brescia, BS, Italy
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Viagrande, CT, Italy
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Florence, FI, Italy
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Milan, MI, Italy
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Milan, MI, Italy
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Rozzano, MI, Italy
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Modena, MO, Italy
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Roma, RM, Italy
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Roma, RM, Italy
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Verona, VR, Italy
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Napoli, , Italy
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Napoli, , Italy
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Fukuoka, Fukuoka, Japan
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Osaka, Osaka, Japan
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Chuo Ku, Tokyo, Japan
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Beirut, , Lebanon
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El Achrafiyé, , Lebanon
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Amsterdam, , Netherlands
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Gliwice, Silesian Voivodeship, Poland
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Poznan, , Poland
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Rostov-on-Don, , Russia
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Riyadh, , Saudi Arabia
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Bratislava, Slovak Republic, Slovakia
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Parktown, , South Africa
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Seoul, Korea, South Korea
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Seoul, Seocho Gu, South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seville, Andalusia, Spain
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Barcelona, Catalonia, Spain
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L'Hospitalet de Llobregat, Catalonia, Spain
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Taipei, Taiwan, ROC, Taiwan
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Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwan
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Kaohsiung City, , Taiwan
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Taichung, , Taiwan
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Taipei, , Taiwan
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Bangkok, THA, Thailand
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Chiang Mai, , Thailand
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Gaziantep, , Turkey (Türkiye)
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Istanbul, , Turkey (Türkiye)
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Glasgow, Scotland, United Kingdom
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Cambridge, , United Kingdom
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London, , United Kingdom
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London, , United Kingdom
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Manchester, , United Kingdom
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Southampton, , United Kingdom
Countries
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References
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Chan DL, Yao JC, Carnaghi C, Buzzoni R, Herbst F, Ridolfi A, Strosberg J, Kulke MH, Pavel M, Singh S. Markers of Systemic Inflammation in Neuroendocrine Tumors: A Pooled Analysis of the RADIANT-3 and RADIANT-4 Studies. Pancreas. 2021 Feb 1;50(2):130-137. doi: 10.1097/MPA.0000000000001745.
Buzzoni R, Carnaghi C, Strosberg J, Fazio N, Singh S, Herbst F, Ridolfi A, Pavel ME, Wolin EM, Valle JW, Oh DY, Yao JC, Pommier R. Impact of prior therapies on everolimus activity: an exploratory analysis of RADIANT-4. Onco Targets Ther. 2017 Oct 16;10:5013-5030. doi: 10.2147/OTT.S142087. eCollection 2017.
Fazio N, Buzzoni R, Delle Fave G, Tesselaar ME, Wolin E, Van Cutsem E, Tomassetti P, Strosberg J, Voi M, Bubuteishvili-Pacaud L, Ridolfi A, Herbst F, Tomasek J, Singh S, Pavel M, Kulke MH, Valle JW, Yao JC. Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis. Cancer Sci. 2018 Jan;109(1):174-181. doi: 10.1111/cas.13427. Epub 2017 Nov 9.
Pavel ME, Singh S, Strosberg JR, Bubuteishvili-Pacaud L, Degtyarev E, Neary MP, Carnaghi C, Tomasek J, Wolin E, Raderer M, Lahner H, Valle JW, Pommier R, Van Cutsem E, Tesselaar MET, Fave GD, Buzzoni R, Hunger M, Eriksson J, Cella D, Ricci JF, Fazio N, Kulke MH, Yao JC. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1411-1422. doi: 10.1016/S1470-2045(17)30471-0. Epub 2017 Aug 30.
Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, Tomasek J, Raderer M, Lahner H, Voi M, Pacaud LB, Rouyrre N, Sachs C, Valle JW, Fave GD, Van Cutsem E, Tesselaar M, Shimada Y, Oh DY, Strosberg J, Kulke MH, Pavel ME; RAD001 in Advanced Neuroendocrine Tumours, Fourth Trial (RADIANT-4) Study Group. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016 Mar 5;387(10022):968-977. doi: 10.1016/S0140-6736(15)00817-X. Epub 2015 Dec 17.
Other Identifiers
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2011-002887-26
Identifier Type: REGISTRY
Identifier Source: secondary_id
CRAD001T2302
Identifier Type: -
Identifier Source: org_study_id
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