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Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors (RADIANT-3)

Primary Purpose

Advanced Neuroendocrine Tumors of Pancreatic Origin

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Everolimus
Everolimus Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Neuroendocrine Tumors of Pancreatic Origin focused on measuring Phase III, Advanced Neuroendocrine Tumor in adults, RAD001, NET, everolimus, mTOr, islet cell, neuroendocrine

Eligibility Criteria

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

Inclusion criteria:

  1. Patients must have advanced (unresectable or metastatic) biopsy-proven pancreatic NET
  2. Measurable disease by radiologic assessment
  3. Adequate blood work
  4. Performance Status 0-2 : Ability to be out of bed most of the time
  5. Adult male or female patients ≥ 18 years of age
  6. Women of childbearing potential must have a negative serum pregnancy test
  7. Written informed consent from patients must be obtained in accordance to local guidelines

Exclusion criteria:

  1. Patients with severe kind of (poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma) cancer are not eligible
  2. Other chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to starting this trial
  3. Hepatic artery procedure called embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of enrollment
  4. Prior therapy with the same kind of medication (mTOR inhibitors: sirolimus, temsirolimus, everolimus).
  5. Uncontrolled diabetes mellitus Patients who have any severe and/or uncontrolled medical conditions such as:
  6. Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
  7. Patients with a known history of HIV seropositivity
  8. No other prior or concurrent cancer at the time enrolling to this trial

Other protocol defined inclusion/ exclusion criteria applied

Sites / Locations

  • University of South Alabama / Mitchell Cancer Institute Deptof Mitchell Cancer Inst(2)
  • Pacific Cancer Medical Center, Inc.
  • Cedars Sinai Medical Center SC-2
  • University of California at Los Angeles UCLA (3)
  • University of California San Francisco Dept. of UCSF Comp. Cancer
  • Kaiser Permanente Northwest Franklin Medical Offices
  • H. Lee Moffitt Cancer Center & Research Institute Malignant Hematology Clinic
  • Indiana University Health Goshen Center for Cancer Dept. of Indiana Univ. Cancer
  • University of Iowa Medical Center Dept. of Iowa Medical Center
  • University of Louisville / James Graham Brown Cancer Center SC
  • LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Dept. of Neuroendocrine Clinic
  • Boston Medical Center BMC
  • Wayne State University/Karmanos Cancer Institute Dept.of KarmanosCancerInst (4)
  • Mayo Clinic - Rochester
  • Littleton Regional Hospital Dept. of Hematology/Oncology
  • Columbia University Medical Center- New York Presbyterian Dept. of Columbia Med. Center
  • Levine Cancer Institute
  • Ohio State Comprehensive Cancer Center/James Cancer Hospital Dept. of OHSU Medical Center
  • Oregon Health & Science University Dept. of OHSU (3)
  • St. Luke's Hospital and Health Network St. Luke's Cancer Network
  • Fox Chase Cancer Center
  • University of Pittsburgh Medical Center Hillman Cancer Center
  • The Center for Cancer and Blood Disorders
  • University of Texas/MD Anderson Cancer Center Dept of MD Anderson CancerCent
  • Novartis Investigative Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Everolimus 10 mg/day

Placebo

Arm Description

Participants received 10 mg per day of Everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).

Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).

Outcomes

Primary Outcome Measures

Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology
Progression of disease is defined as the time from study start to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria: Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.

Secondary Outcome Measures

Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response})
Objective Response defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of the longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks . Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions
Overall Survival
Overall survival (OS) was defined as the time from date of randomization to the date of death due to any cause. Analyses were performed using all deaths in the FAS population regardless of whether they were observed during the double-blind treatment period, the open-label treatment period, the post-treatment evaluations, or the survival follow-up period.
Progression Free Survival According to Ki-67 Levels Categorized as: Less Than or Equal to 2%, > 2% to Less Than or Equal to 5% and > 5%
The level of Ki 67 expression for evaluable tumor samples were analyzed towards progression free survival (PFS) as per local investigator assessment. The Ki-67 protein is a cellular marker for proliferation. It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Baseline Ki 67 levels were categorized as: less than or equal to 2%, > 2% to less than or equal to 5% and > 5%.
Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response
Baseline levels of serum CgA SE were characterized towards progression free survival (PFS) as per local investigator assessment, relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated' otherwise considered as "Non-elevated". An 'early response' (applicable to only those patients with elevated levels at baseline) was defined as a decrease of greater than or equal to 30% from baseline to Cycle 2 Day 1 or normalization by Cycle 2 Day 1. CgA is widely expressed in well-differentiated pancreatic NET. CgA is present in the secretory granules of neuroendocrine cells. Pancreatic NET patients often present with elevated circulating levels of CgA in their blood. Baseline levels of these biomarkers are considered as prognostic factors.
Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response
Baseline levels of serum NSE were characterized towards PFS as per local investigator assessment, relative to the upper limited of normal (ULN). NSE levels exceeding ULN were considered to be 'Elevated' otherwise considered as "Non-elevated". An 'early response' (applicable to only those patients with elevated levels at baseline) was defined as a decrease of greater than or equal to 30% from baseline to Cycle 2 Day 1 or normalization by Cycle 2 Day 1. NSE is widely expressed in well-differentiated pancreatic NET. NSE is usually expressed in the cytoplasm. Pancreatic NET patients often present with elevated circulating levels of NSE in their blood. Baseline levels of these biomarkers are considered as prognostic factors.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs)
Adverse events 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. Serious adverse events 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 Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) (Open-label Period)
Adverse events 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. Serious adverse events 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.
Evaluation of Pharmacokinetics (PK) Parameter: AUC0-t Last
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. This PK parameter is area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last).
Evaluation of Pharmacokinetics (PK) Parameters: Cmax, Cmin
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameter: maximum (peak) drug concentration (Cmax) and minimum (trough) drug concentration (Cmin).
Evaluation of Pharmacokinetics (PK) Parameter: CL/F
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameter clearance of distribution expressed as a function of bioavailability (CL/F).
Evaluation of Pharmacokinetics (PK) Parameter: Tmax -Time to Maximum (Peak) Drug Concentration
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. Values for tmax where summarized in median (range).
Analysis of Time to Definitive Deterioration of WHO Performance Status Using Kaplan-Meier
Time to definitive worsening is defined as a definitive increase in performance status from a baseline of 0 or 1 to WHO >= 2, or from a baseline value of 2 to WHO >= 3. If no earlier deterioration, patients were censored at the end of follow-up or at the start of further antineoplastic therapy. Rates of patients with no deterioration at 3 and 6 months were computed using Kaplan-meier method. Grade 0: Able to carry out all activity without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory & able to do light work; Grade 2: Ambulatory & capable of all self-care but unable to carry out any work. Up & about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled & cannot carry on any self-care; totally confined to bed or chair.
Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF)
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Plasma Angiogenesis Marker: Placental Growth Factor (PLGF)
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1)
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF)
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.

Full Information

First Posted
July 31, 2007
Last Updated
June 4, 2015
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00510068
Brief Title
Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors
Acronym
RADIANT-3
Official Title
A Randomized Double-blind Phase III Study of RAD001 10 mg/d Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Pancreatic Neuroendocrine Tumor (NET)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study was to evaluate progression free survival in those participants assigned everolimus 10 mg/day plus Best Supportive Care versus those assigned to placebo plus Best Supportive Care in Advanced Neuroendocrine Tumors of pancreatic origin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Neuroendocrine Tumors of Pancreatic Origin
Keywords
Phase III, Advanced Neuroendocrine Tumor in adults, RAD001, NET, everolimus, mTOr, islet cell, neuroendocrine

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Everolimus 10 mg/day
Arm Type
Experimental
Arm Description
Participants received 10 mg per day of Everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
A 10-mg dose of everolimus was given by continuous oral daily dosing of two 5-mg tablets.
Intervention Type
Drug
Intervention Name(s)
Everolimus Placebo
Intervention Description
a 10-mg dose of matching placebo to Everolimus was given by continuous oral daily dosing of two 5-mg tablets.
Primary Outcome Measure Information:
Title
Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology
Description
Progression of disease is defined as the time from study start to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria: Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
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, 17 August 2007, until cut-off date 28 February 2010
Secondary Outcome Measure Information:
Title
Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response})
Description
Objective Response defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of the longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks . Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions
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, 17 August 2007, until cut-off date 28 February 2010
Title
Overall Survival
Description
Overall survival (OS) was defined as the time from date of randomization to the date of death due to any cause. Analyses were performed using all deaths in the FAS population regardless of whether they were observed during the double-blind treatment period, the open-label treatment period, the post-treatment evaluations, or the survival follow-up period.
Time Frame
Baseline, to death- no time limit
Title
Progression Free Survival According to Ki-67 Levels Categorized as: Less Than or Equal to 2%, > 2% to Less Than or Equal to 5% and > 5%
Description
The level of Ki 67 expression for evaluable tumor samples were analyzed towards progression free survival (PFS) as per local investigator assessment. The Ki-67 protein is a cellular marker for proliferation. It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Baseline Ki 67 levels were categorized as: less than or equal to 2%, > 2% to less than or equal to 5% and > 5%.
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, 17 August 2007, until cut-off date 28 February 2010
Title
Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response
Description
Baseline levels of serum CgA SE were characterized towards progression free survival (PFS) as per local investigator assessment, relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated' otherwise considered as "Non-elevated". An 'early response' (applicable to only those patients with elevated levels at baseline) was defined as a decrease of greater than or equal to 30% from baseline to Cycle 2 Day 1 or normalization by Cycle 2 Day 1. CgA is widely expressed in well-differentiated pancreatic NET. CgA is present in the secretory granules of neuroendocrine cells. Pancreatic NET patients often present with elevated circulating levels of CgA in their blood. Baseline levels of these biomarkers are considered as prognostic factors.
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, 17 August 2007, until cut-off date 28 February 2010
Title
Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response
Description
Baseline levels of serum NSE were characterized towards PFS as per local investigator assessment, relative to the upper limited of normal (ULN). NSE levels exceeding ULN were considered to be 'Elevated' otherwise considered as "Non-elevated". An 'early response' (applicable to only those patients with elevated levels at baseline) was defined as a decrease of greater than or equal to 30% from baseline to Cycle 2 Day 1 or normalization by Cycle 2 Day 1. NSE is widely expressed in well-differentiated pancreatic NET. NSE is usually expressed in the cytoplasm. Pancreatic NET patients often present with elevated circulating levels of NSE in their blood. Baseline levels of these biomarkers are considered as prognostic factors.
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, 17 August 2007, until cut-off date 28 February 2010
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs)
Description
Adverse events 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. Serious adverse events 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.
Time Frame
on or after the start of double-blind study medication until no later than 28 days after double-blind study medication discontinuation
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) (Open-label Period)
Description
Adverse events 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. Serious adverse events 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.
Time Frame
on or after the start of open-label study medication until no later than 28 days after open-label study medication discontinuation
Title
Evaluation of Pharmacokinetics (PK) Parameter: AUC0-t Last
Description
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. This PK parameter is area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last).
Time Frame
Day 1 of every cycle (28 days/cycle) throughout the study
Title
Evaluation of Pharmacokinetics (PK) Parameters: Cmax, Cmin
Description
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameter: maximum (peak) drug concentration (Cmax) and minimum (trough) drug concentration (Cmin).
Time Frame
Day 1 of every cycle (28 days/cycle) throughout the study
Title
Evaluation of Pharmacokinetics (PK) Parameter: CL/F
Description
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameter clearance of distribution expressed as a function of bioavailability (CL/F).
Time Frame
Day 1 of every cycle (28 days/cycle) throughout the study
Title
Evaluation of Pharmacokinetics (PK) Parameter: Tmax -Time to Maximum (Peak) Drug Concentration
Description
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. Values for tmax where summarized in median (range).
Time Frame
Day 1 of every cycle (28 days/cycle) throughout the study
Title
Analysis of Time to Definitive Deterioration of WHO Performance Status Using Kaplan-Meier
Description
Time to definitive worsening is defined as a definitive increase in performance status from a baseline of 0 or 1 to WHO >= 2, or from a baseline value of 2 to WHO >= 3. If no earlier deterioration, patients were censored at the end of follow-up or at the start of further antineoplastic therapy. Rates of patients with no deterioration at 3 and 6 months were computed using Kaplan-meier method. Grade 0: Able to carry out all activity without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory & able to do light work; Grade 2: Ambulatory & capable of all self-care but unable to carry out any work. Up & about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled & cannot carry on any self-care; totally confined to bed or chair.
Time Frame
3 months, 6 months
Title
Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF)
Description
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame
Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Title
Plasma Angiogenesis Marker: Placental Growth Factor (PLGF)
Description
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame
Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Title
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1)
Description
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame
Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Title
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)
Description
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame
Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Title
Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF)
Description
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame
Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Patients must have advanced (unresectable or metastatic) biopsy-proven pancreatic NET Measurable disease by radiologic assessment Adequate blood work Performance Status 0-2 : Ability to be out of bed most of the time Adult male or female patients ≥ 18 years of age Women of childbearing potential must have a negative serum pregnancy test Written informed consent from patients must be obtained in accordance to local guidelines Exclusion criteria: Patients with severe kind of (poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma) cancer are not eligible Other chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to starting this trial Hepatic artery procedure called embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of enrollment Prior therapy with the same kind of medication (mTOR inhibitors: sirolimus, temsirolimus, everolimus). Uncontrolled diabetes mellitus Patients who have any severe and/or uncontrolled medical conditions such as: Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent Patients with a known history of HIV seropositivity No other prior or concurrent cancer at the time enrolling to this trial Other protocol defined inclusion/ exclusion criteria applied
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 South Alabama / Mitchell Cancer Institute Deptof Mitchell Cancer Inst(2)
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36688
Country
United States
Facility Name
Pacific Cancer Medical Center, Inc.
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Cedars Sinai Medical Center SC-2
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of California at Los Angeles UCLA (3)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California San Francisco Dept. of UCSF Comp. Cancer
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0128
Country
United States
Facility Name
Kaiser Permanente Northwest Franklin Medical Offices
City
Denver
State/Province
Colorado
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute Malignant Hematology Clinic
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Indiana University Health Goshen Center for Cancer Dept. of Indiana Univ. Cancer
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa Medical Center Dept. of Iowa Medical Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Louisville / James Graham Brown Cancer Center SC
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Dept. of Neuroendocrine Clinic
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
Boston Medical Center BMC
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute Dept.of KarmanosCancerInst (4)
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic - Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Littleton Regional Hospital Dept. of Hematology/Oncology
City
Littleton
State/Province
New Hampshire
ZIP/Postal Code
03561
Country
United States
Facility Name
Columbia University Medical Center- New York Presbyterian Dept. of Columbia Med. Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Ohio State Comprehensive Cancer Center/James Cancer Hospital Dept. of OHSU Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oregon Health & Science University Dept. of OHSU (3)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
St. Luke's Hospital and Health Network St. Luke's Cancer Network
City
Bethlehem
State/Province
Pennsylvania
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111-2497
Country
United States
Facility Name
University of Pittsburgh Medical Center Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
The Center for Cancer and Blood Disorders
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
University of Texas/MD Anderson Cancer Center Dept of MD Anderson CancerCent
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Fortaleza
State/Province
CE
ZIP/Postal Code
60430-370
Country
Brazil
Facility Name
Novartis Investigative Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Novartis Investigative Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
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
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Novartis Investigative Site
City
Besancon Cedex
ZIP/Postal Code
25030
Country
France
Facility Name
Novartis Investigative Site
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Novartis Investigative Site
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Novartis Investigative Site
City
Lille Cedex
ZIP/Postal Code
59020
Country
France
Facility Name
Novartis Investigative Site
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Novartis Investigative Site
City
Marseille cedex 05
ZIP/Postal Code
13385
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier Cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Novartis Investigative Site
City
Paris Cedex 13
ZIP/Postal Code
75651
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
Novartis Investigative Site
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse Cedex 4
ZIP/Postal Code
31054
Country
France
Facility Name
Novartis Investigative Site
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
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
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Novartis Investigative Site
City
Marburg
ZIP/Postal Code
35033
Country
Germany
Facility Name
Novartis Investigative Site
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
State/Province
GR
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
GR-115 22
Country
Greece
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20141
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Facility Name
Novartis Investigative Site
City
Modena
State/Province
MO
ZIP/Postal Code
41100
Country
Italy
Facility Name
Novartis Investigative Site
City
Pisa
State/Province
PI
ZIP/Postal Code
56124
Country
Italy
Facility Name
Novartis Investigative Site
City
Kashiwa
State/Province
Chiba
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka-city
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Chuo-ku
State/Province
Tokyo
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
110 744
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
738-736
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Martin
State/Province
Slovak Republic
ZIP/Postal Code
036 59
Country
Slovakia
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
Cataluña
ZIP/Postal Code
08907
Country
Spain
Facility Name
Novartis Investigative Site
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden
Facility Name
Novartis Investigative Site
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Taipei
State/Province
Taiwan, ROC
ZIP/Postal Code
112
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Lin-Ko
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Novartis Investigative Site
City
Songkla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Novartis Investigative Site
City
Withington
State/Province
Greater Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom

12. IPD Sharing Statement

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
28113028
Citation
Yao JC, Voi M, Lincy J, Pavel M. Reply to V. Amoroso et al. J Clin Oncol. 2017 May 1;35(13):1488-1489. doi: 10.1200/JCO.2017.71.3875. Epub 2017 Jan 23. No abstract available.
Results Reference
derived
PubMed Identifier
27621394
Citation
Yao JC, Pavel M, Lombard-Bohas C, Van Cutsem E, Voi M, Brandt U, He W, Chen D, Capdevila J, de Vries EGE, Tomassetti P, Hobday T, Pommier R, Oberg K. Everolimus for the Treatment of Advanced Pancreatic Neuroendocrine Tumors: Overall Survival and Circulating Biomarkers From the Randomized, Phase III RADIANT-3 Study. J Clin Oncol. 2016 Nov 10;34(32):3906-3913. doi: 10.1200/JCO.2016.68.0702. Epub 2016 Sep 30.
Results Reference
derived
PubMed Identifier
25479584
Citation
Lombard-Bohas C, Yao JC, Hobday T, Van Cutsem E, Wolin EM, Panneerselvam A, Stergiopoulos S, Shah MH, Capdevila J, Pommier R. Impact of prior chemotherapy use on the efficacy of everolimus in patients with advanced pancreatic neuroendocrine tumors: a subgroup analysis of the phase III RADIANT-3 trial. Pancreas. 2015 Mar;44(2):181-9. doi: 10.1097/MPA.0000000000000262.
Results Reference
derived
PubMed Identifier
21306238
Citation
Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Oberg K; RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):514-23. doi: 10.1056/NEJMoa1009290.
Results Reference
derived
Links:
URL
http://radiantclinicaltrials.com
Description
Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Learn more about this trial

Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors

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