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Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin) (RADIANT-4)

Primary Purpose

Advanced NET of GI Origin, Advanced NET of Lung Origin, Neuroendocrine Tumors

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Everolimus
Placebo
Best suportive care (BSC)
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced NET of GI Origin focused on measuring Neuroendocrine tumor, NET, progressive, advanced, gastrointestinal, GI or lung origin, nonfunctional, everolimus, Advanced NET of GI origin, Advanced NET of lung origin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin
  • 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 poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma
  • 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

Other protocol-defined inclusion/exclusion criteria might apply.

Sites / Locations

  • University of California San Diego - Moores Cancer Center Regulatory
  • Scripps Clinic Regulatory
  • Cedars Sinai Medical Center SC
  • University of Colorado Cancer Centre SC
  • H Lee Moffitt Cancer Center and Research Institute HLM
  • University of Chicago UC SC
  • Goshen Center for Cancer Care IU Health SC
  • Dana Farber Cancer Institute SC
  • Montefiore Medical Center MMC
  • Memorial Sloan Kettering MSkCC SC
  • Oregon Health and Science University OH&SU
  • Vanderbilt University Medical Center Vanderbilt Med Ctr
  • Texas Oncology P A Texas Oncology Amarillo
  • Texas Oncology P A TX Oncology Baylor
  • University of Texas Southwestern Medical Center
  • University of Texas MD Anderson Cancer Center UT MD Anderson Cancer Ctr
  • University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc
  • Novartis Investigative Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Everolimus + BSC

Placebo + BSC

Arm Description

Participants received everolimus 10 mg once daily plus best supportive care (BSC) throughout the study

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.

Outcomes

Primary Outcome Measures

Probability of Participants Remaining Event-Free in Progression-Free Survival (PFS) Based on Central Radiology Assessment
PFS is defined as the time from randomization to the date of the first documented tumor progression or death from any cause, whichever comes first. Progression was defined using modified RECIST 1.0 and as per central radiology assessment as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Progression was assessed by cat scan (CT) and/or magnetic resonance imaging (MRI). For participants who had not progressed or died at the analysis cut-off date, PFS was censored at the date of the last adequate tumor evaluation date. An adequate tumour assessment is a tumour assessment with an overall response other than unknown. The percentage event-free probability estimate is the estimated probability that a patient will remain event-free in PFS up to the specified time point.

Secondary Outcome Measures

Overall Survival (OS)
OS is defined as the time from the date of randomization to date of death due to any cause. If a death had not been observed by the date of analysis cut-off, then OS was censored at the date of last contact. All participants randomized to placebo arm who crossed over to everolimus were censored.
Overall Response Rate (ORR) as Per Modified RECIST 1.0 According to Central Evaluation
ORR is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), according to central evaluation and as per modified RECIST 1.0. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.
Disease Control Rate (DCR) Based on Modified RECIST 1.0 and as Per Central Radiology Assessment
DCR is defined as the proportion of subjects with best overall response of CR or PR or stable disease based on modified RECIST 1.0 and as per central radiology assessment. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. Stable disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Time to Definitive Deterioration in Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire Total Score
FACT-G is a self-assessed health-related quality of life questionnaire. The questionnaire is comprised of 27 questions examining physical, social/family, emotional, and functional well-being. Participants responded to the items on a five-point scale, ranging from 0: "Not at all" to 4: "Very much." The total score ranges from 0 to 108, with higher scores indicating a better patient-reported outcome/quality of life. Definitive deterioration is defined as a decrease in the total score by at least 7 points compared to baseline with no further improvement. Death was considered as worsening of the FACT-G total score if it occurred close to the last available assessment, where "close" was defined as twice the planned period between two assessments. Patients without definitive worsening prior to analysis cut-off or prior to start of another anticancer therapy were censored at the date of their last assessment.
Change From Baseline in Chromogranin A (CgA) Levels
CgA is a potential biomarker for tumor response. Blood samples were collected for assessment of CgA levels. Change from Baseline at a particular visit was calculated as the CgA level at that visit minus Baseline.
Change From Baseline in Neuron Specific Enolase (NSE) Levels
NSE is a potential biomarker for tumor response. Blood samples were collected for assessment of NSE levels. Change from Baseline at a particular visit was calculated as the NSE level at that visit minus Baseline.
Time to Definitive Deterioration in World Health Organization (WHO) Performance Status (PS) Change
WHO PS is a scale rated from 0 (fully active) to 5 (death) by a healthcare professional to assess the overall status of a patient: a lower score represents a higher ability to perform daily tasks. Deterioration is defined as an increase of at least one point compared to baseline. Deterioration is considered definitive if no improvements in the WHO PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed. Death was considered as worsening of the WHO PS if it occurred close to the last available assessment, where "close" was defined as twice the planned period between two assessments. Patients without definitive worsening prior to analysis cut-off or prior to start of another anticancer therapy were censored at the date of their last assessment.
Pharmacokinetics (PK): Predose Concentration (Cmin) of Everolimus at Day 29
A pre-dose blood sample at day 29 was collected to determine the exposure of everolimus at the steady-state pre-dose concentration (Cmin). Cmin is provided for participants randomized to everolimus+BSC who received 10mg of everolimus daily and also for participants randomized to everolimus+BSC who received 5mg of everolimus daily which was required for a number of participants in the study experiencing adverse events requiring dose modifications

Full Information

First Posted
December 22, 2011
Last Updated
July 13, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01524783
Brief Title
Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin)
Acronym
RADIANT-4
Official Title
A Randomized, Double-blind, Multicenter, Phase III Study of Everolimus (RAD001) Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced NET of GI or Lung Origin
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
March 30, 2012 (Actual)
Primary Completion Date
November 28, 2014 (Actual)
Study Completion Date
August 7, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to compare the antitumor activity of everolimus plus best supportive care versus placebo plus best supportive care in patients with progressive nonfunctional neuroendocrine tumor (NET) of gastrointestinal (GI) or lung origin without a history of, or current symptoms of carcinoid syndrome.
Detailed Description
This was a prospective, multi-center, randomized, double-blind, parallel-group, placebo-controlled, two-arm Phase III study comparing the efficacy and safety of everolimus 10 mg daily to placebo in patients with advanced NET of GI or lung origin without a history of, or current symptoms of carcinoid syndrome. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced NET of GI Origin, Advanced NET of Lung Origin, Neuroendocrine Tumors
Keywords
Neuroendocrine tumor, NET, progressive, advanced, gastrointestinal, GI or lung origin, nonfunctional, everolimus, Advanced NET of GI origin, Advanced NET of lung origin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
302 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Everolimus + BSC
Arm Type
Experimental
Arm Description
Participants received everolimus 10 mg once daily plus best supportive care (BSC) throughout the study
Arm Title
Placebo + BSC
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Participants were treated with everolimus 10 mg (two 5 mg tablets) once daily orally taken
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants were treated with two tablets of matching placebo once daily orally taken.
Intervention Type
Other
Intervention Name(s)
Best suportive care (BSC)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Probability of Participants Remaining Event-Free in Progression-Free Survival (PFS) Based on Central Radiology Assessment
Description
PFS is defined as the time from randomization to the date of the first documented tumor progression or death from any cause, whichever comes first. Progression was defined using modified RECIST 1.0 and as per central radiology assessment as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Progression was assessed by cat scan (CT) and/or magnetic resonance imaging (MRI). For participants who had not progressed or died at the analysis cut-off date, PFS was censored at the date of the last adequate tumor evaluation date. An adequate tumour assessment is a tumour assessment with an overall response other than unknown. The percentage event-free probability estimate is the estimated probability that a patient will remain event-free in PFS up to the specified time point.
Time Frame
From date of randomization to progression or death, whichever comes first, assessed up to 27 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS is defined as the time from the date of randomization to date of death due to any cause. If a death had not been observed by the date of analysis cut-off, then OS was censored at the date of last contact. All participants randomized to placebo arm who crossed over to everolimus were censored.
Time Frame
From date of randomization to date of death, assessed up to approximately 8 years
Title
Overall Response Rate (ORR) as Per Modified RECIST 1.0 According to Central Evaluation
Description
ORR is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), according to central evaluation and as per modified RECIST 1.0. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.
Time Frame
From randomization until end of treatment, assessed up to approximately 2.5 years
Title
Disease Control Rate (DCR) Based on Modified RECIST 1.0 and as Per Central Radiology Assessment
Description
DCR is defined as the proportion of subjects with best overall response of CR or PR or stable disease based on modified RECIST 1.0 and as per central radiology assessment. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. Stable disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Time Frame
From randomization until end of treatment, assessed up to approximately 2.5 years
Title
Time to Definitive Deterioration in Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire Total Score
Description
FACT-G is a self-assessed health-related quality of life questionnaire. The questionnaire is comprised of 27 questions examining physical, social/family, emotional, and functional well-being. Participants responded to the items on a five-point scale, ranging from 0: "Not at all" to 4: "Very much." The total score ranges from 0 to 108, with higher scores indicating a better patient-reported outcome/quality of life. Definitive deterioration is defined as a decrease in the total score by at least 7 points compared to baseline with no further improvement. Death was considered as worsening of the FACT-G total score if it occurred close to the last available assessment, where "close" was defined as twice the planned period between two assessments. Patients without definitive worsening prior to analysis cut-off or prior to start of another anticancer therapy were censored at the date of their last assessment.
Time Frame
From randomization to definitive deterioration of FACT-G total score, assessed up to approximately 3 years
Title
Change From Baseline in Chromogranin A (CgA) Levels
Description
CgA is a potential biomarker for tumor response. Blood samples were collected for assessment of CgA levels. Change from Baseline at a particular visit was calculated as the CgA level at that visit minus Baseline.
Time Frame
From baseline (every 4 weeks) up to 116 weeks
Title
Change From Baseline in Neuron Specific Enolase (NSE) Levels
Description
NSE is a potential biomarker for tumor response. Blood samples were collected for assessment of NSE levels. Change from Baseline at a particular visit was calculated as the NSE level at that visit minus Baseline.
Time Frame
From baseline (every 4 weeks) up to Week 116
Title
Time to Definitive Deterioration in World Health Organization (WHO) Performance Status (PS) Change
Description
WHO PS is a scale rated from 0 (fully active) to 5 (death) by a healthcare professional to assess the overall status of a patient: a lower score represents a higher ability to perform daily tasks. Deterioration is defined as an increase of at least one point compared to baseline. Deterioration is considered definitive if no improvements in the WHO PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed. Death was considered as worsening of the WHO PS if it occurred close to the last available assessment, where "close" was defined as twice the planned period between two assessments. Patients without definitive worsening prior to analysis cut-off or prior to start of another anticancer therapy were censored at the date of their last assessment.
Time Frame
From randomization to definitive deterioration of WHO performance status, assessed up to approximately 3 years
Title
Pharmacokinetics (PK): Predose Concentration (Cmin) of Everolimus at Day 29
Description
A pre-dose blood sample at day 29 was collected to determine the exposure of everolimus at the steady-state pre-dose concentration (Cmin). Cmin is provided for participants randomized to everolimus+BSC who received 10mg of everolimus daily and also for participants randomized to everolimus+BSC who received 5mg of everolimus daily which was required for a number of participants in the study experiencing adverse events requiring dose modifications
Time Frame
Pre-dose at Day 29.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin 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 poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma 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 Other protocol-defined inclusion/exclusion criteria might apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Diego - Moores Cancer Center Regulatory
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Scripps Clinic Regulatory
City
La Jolla
State/Province
California
ZIP/Postal Code
92121
Country
United States
Facility Name
Cedars Sinai Medical Center SC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of Colorado Cancer Centre SC
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
H Lee Moffitt Cancer Center and Research Institute HLM
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of Chicago UC SC
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Goshen Center for Cancer Care IU Health SC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Dana Farber Cancer Institute SC
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Montefiore Medical Center MMC
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Memorial Sloan Kettering MSkCC SC
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Oregon Health and Science University OH&SU
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Vanderbilt University Medical Center Vanderbilt Med Ctr
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Texas Oncology P A Texas Oncology Amarillo
City
Dallas
State/Province
Texas
ZIP/Postal Code
75251
Country
United States
Facility Name
Texas Oncology P A TX Oncology Baylor
City
Dallas
State/Province
Texas
ZIP/Postal Code
75251
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center UT MD Anderson Cancer Ctr
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States
Facility Name
Novartis Investigative Site
City
Innsbruck
State/Province
Tyrol
ZIP/Postal Code
6020
Country
Austria
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Edegem
State/Province
Antwerpen
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Novartis Investigative Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Facility Name
Novartis Investigative Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Novartis Investigative Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Novartis Investigative Site
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100021
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100036
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100039
Country
China
Facility Name
Novartis Investigative Site
City
Bogotá
State/Province
Cundinamarca
Country
Colombia
Facility Name
Novartis Investigative Site
City
Brno
ZIP/Postal Code
65653
Country
Czechia
Facility Name
Novartis Investigative Site
City
Olomouc
ZIP/Postal Code
775 20
Country
Czechia
Facility Name
Novartis Investigative Site
City
Praha
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Novartis Investigative Site
City
Bad Berka
ZIP/Postal Code
99438
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
Novartis Investigative Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1062
Country
Hungary
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1085
Country
Hungary
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Brescia
State/Province
BS
ZIP/Postal Code
25123
Country
Italy
Facility Name
Novartis Investigative Site
City
Viagrande
State/Province
CT
ZIP/Postal Code
95029
Country
Italy
Facility Name
Novartis Investigative Site
City
Firenze
State/Province
FI
ZIP/Postal Code
50134
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20141
Country
Italy
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Modena
State/Province
MO
ZIP/Postal Code
41124
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00168
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00189
Country
Italy
Facility Name
Novartis Investigative Site
City
Verona
State/Province
VR
ZIP/Postal Code
37126
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80132
Country
Italy
Facility Name
Novartis Investigative Site
City
Fukuoka city
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka-city
State/Province
Osaka
ZIP/Postal Code
553-0003
Country
Japan
Facility Name
Novartis Investigative Site
City
Chuo ku
State/Province
Tokyo
ZIP/Postal Code
104 0045
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Seocho Gu
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Ashrafieh
ZIP/Postal Code
166830
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Beirut
ZIP/Postal Code
1107 2020
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Gliwice
State/Province
Slaskie
ZIP/Postal Code
44-101
Country
Poland
Facility Name
Novartis Investigative Site
City
Poznan
ZIP/Postal Code
60-355
Country
Poland
Facility Name
Novartis Investigative Site
City
Rostov-na-Donu
ZIP/Postal Code
344037
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Riyadh
ZIP/Postal Code
11211
Country
Saudi Arabia
Facility Name
Novartis Investigative Site
City
Bratislava
State/Province
Slovak Republic
ZIP/Postal Code
833 10
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Parktown
ZIP/Postal Code
2193
Country
South Africa
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41009
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Hospitalet de LLobregat
State/Province
Catalunya
ZIP/Postal Code
08907
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
State/Province
Taiwan, ROC
ZIP/Postal Code
11217
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Kuei-Shan Chiang
State/Province
Taoyuan/ Taiwan ROC
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Kaohsiung
ZIP/Postal Code
833
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
State/Province
THA
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Novartis Investigative Site
City
Gaziantep
ZIP/Postal Code
27310
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34303
Country
Turkey
Facility Name
Novartis Investigative Site
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Cambridge
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M20 2BX
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
33560090
Citation
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.
Results Reference
derived
PubMed Identifier
29081664
Citation
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.
Results Reference
derived
PubMed Identifier
29055056
Citation
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.
Results Reference
derived
PubMed Identifier
28838862
Citation
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.
Results Reference
derived
PubMed Identifier
26703889
Citation
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.
Results Reference
derived

Learn more about this trial

Everolimus Plus Best Supportive Care vs Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (GI or Lung Origin)

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