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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00510068
First received: July 31, 2007
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Advanced Neuroendocrine Tumors
Drug: Everolimus
Drug: Placebo to Everolimus
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology [ 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 ] [ Designated as safety issue: No ]
    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}) [ 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 ] [ Designated as safety issue: No ]
    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

  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) [ Time Frame: on or after the start of double-blind study medication until no later than 28 days after double-blind study medication discontinuation ] [ Designated as safety issue: Yes ]
    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 to Overall Survival [ Time Frame: Baseline, to death- no time limit ] [ Designated as safety issue: Yes ]
    Overall Survival Rate is the time from study start to death from any cause.

  • Evaluation of Pharmacokinetics (PK) Parameters [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ] [ Designated as safety issue: No ]
    The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameters were: area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last), area under the concentration time curve from time zero to time t, where t is the end of the dosing interval (AUC0-t), maximum (peak) drug concentration (Cmax), time to maximum (peak) drug concentration (tmax), and minimum (trough) drug concentration (Cmin).

  • Changes From Baseline in Serum Biochemical Tumor Markers, Such as Chromogranin A (CgA) and Neuron Specific Enolase (NSE) [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) ] [ Designated as safety issue: No ]
    Baseline levels of serum CgA and NSE were characterized relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated". NSE levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated".


Enrollment: 410
Study Start Date: July 2007
Estimated Study Completion Date: December 2017
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus 10 mg/day
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).
Drug: Everolimus
A 10-mg dose of everolimus was given by continuous oral daily dosing of two 5-mg tablets.
Other Name: RAD001
Placebo Comparator: Placebo
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).
Drug: Placebo to Everolimus
a 10-mg dose of matching placebo to Everolimus was given by continuous oral daily dosing of two 5-mg tablets.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00510068

  Hide Study Locations
Locations
United States, Alabama
University of South Alabama / Mitchell Cancer Institute Deptof Mitchell Cancer Inst(2)
Mobile, Alabama, United States, 36688
United States, California
Pacific Cancer Medical Center, Inc.
Anaheim, California, United States, 92801
Cedars Sinai Medical Center SC-2
Los Angeles, California, United States, 90048
University of California at Los Angeles UCLA (3)
Los Angeles, California, United States, 90095
University of California San Francisco Dept. of UCSF Comp. Cancer
San Francisco, California, United States, 94143-0128
United States, Colorado
Kaiser Permanente Northwest Franklin Medical Offices
Denver, Colorado, United States
United States, Florida
H. Lee Moffitt Cancer Center/University of South Florida Malignant Hematology Clinic
Tampa, Florida, United States, 33612
United States, Indiana
Indiana University Health Goshen Center for Cancer Dept. of Indiana Univ. Cancer
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Medical Center Dept. of Iowa Medical Center
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Louisville / James Graham Brown Cancer Center SC
Louisville, Kentucky, United States, 40202
United States, Louisiana
LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Dept. of Neuroendocrine Clinic
New Orleans, Louisiana, United States, 70115
United States, Massachusetts
Boston Medical Center BMC
Boston, Massachusetts, United States, 02118
United States, Michigan
Wayne State University/Karmanos Cancer Institute Dept.of KarmanosCancerInst (4)
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic - Rochester
Rochester, Minnesota, United States, 55905
United States, New Hampshire
Littleton Regional Hospital Dept. of Hematology/Oncology
Littleton, New Hampshire, United States, 03561
United States, New Jersey
Hematology Oncology Associates of Northern New Jersey PA Dept of Hem-Onc of Northern NJ
Morristown, New Jersey, United States, 07962
United States, New York
Columbia University Medical Center- New York Presbyterian Dept. of Columbia Med. Center
New York, New York, United States, 10032
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28203
United States, Ohio
Ohio State Comprehensive Cancer Center/James Cancer Hospital Dept. of OHSU Medical Center
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health & Science University Dept. of OHSU (3)
Portland, Oregon, United States, 97239
United States, Pennsylvania
St. Luke's Hospital and Health Network St. Luke's Cancer Network
Bethlehem, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
University of Pittsburgh Medical Center Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
United States, Texas
The Center for Cancer and Blood Disorders
Fort Worth, Texas, United States, 76104
MD Anderson Cancer Center/University of Texas Dept of MD Anderson CancerCent
Houston, Texas, United States, 77030-4009
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1070
Novartis Investigative Site
Bruxelles, Belgium, 1200
Novartis Investigative Site
Leuven, Belgium, 3000
Brazil
Novartis Investigative Site
Fortaleza, CE, Brazil, 60430-370
Canada, Alberta
Novartis Investigative Site
Calgary, Alberta, Canada, T2N 4N2
Novartis Investigative Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Novartis Investigative Site
London, Ontario, Canada, N6A 4L6
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H1T 2M4
Novartis Investigative Site
Montreal, Quebec, Canada, H3A 1A1
France
Novartis Investigative Site
Besancon Cedex, France, 25030
Novartis Investigative Site
Clichy, France, 92110
Novartis Investigative Site
Dijon, France, 21079
Novartis Investigative Site
Lille Cedex, France, 59020
Novartis Investigative Site
Lyon, France, 69437
Novartis Investigative Site
Marseille cedex 05, France, 13385
Novartis Investigative Site
Montpellier Cedex 5, France, 34298
Novartis Investigative Site
Paris, France, 75015
Novartis Investigative Site
Paris Cedex 13, France, 75651
Novartis Investigative Site
Reims, France, 51092
Novartis Investigative Site
Strasbourg, France, 67098
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Novartis Investigative Site
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site
Bad Berka, Germany, 99438
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Mainz, Germany, D-55101
Novartis Investigative Site
Marburg, Germany, 35033
Novartis Investigative Site
Muenchen, Germany, 81377
Greece
Novartis Investigative Site
Athens, Greece, GR-115 22
Novartis Investigative Site
Athens, Greece, GR 11527
Italy
Novartis Investigative Site
Bologna, BO, Italy, 40138
Novartis Investigative Site
Milano, MI, Italy, 20132
Novartis Investigative Site
Milano, MI, Italy, 20162
Novartis Investigative Site
Milano, MI, Italy, 20141
Novartis Investigative Site
Modena, MO, Italy, 41100
Novartis Investigative Site
Pisa, PI, Italy, 56124
Japan
Novartis Investigative Site
Kashiwa, Chiba, Japan
Novartis Investigative Site
Fukuoka-city, Fukuoka, Japan, 812-8582
Novartis Investigative Site
Chuo-ku, Tokyo, Japan
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 120-752
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 110 744
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 135-710
Novartis Investigative Site
Seoul, Korea, Republic of, 738-736
Netherlands
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Slovakia
Novartis Investigative Site
Martin, Slovak Republic, Slovakia, 036 59
Spain
Novartis Investigative Site
Barcelona, Cataluna, Spain, 08035
Novartis Investigative Site
Hospitalet de LLobregat, Cataluña, Spain, 08907
Sweden
Novartis Investigative Site
Uppsala, Sweden, SE-751 85
Switzerland
Novartis Investigative Site
Zurich, Switzerland, 8091
Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site
Kaohsiung, Taiwan, 807
Novartis Investigative Site
Lin-Ko, Taiwan, 33305
Novartis Investigative Site
Taipei, Taiwan, 10002
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10400
Novartis Investigative Site
Songkla, Thailand, 90110
United Kingdom
Novartis Investigative Site
Withington, Greater Manchester, United Kingdom, M20 4BX
Novartis Investigative Site
Glasgow, United Kingdom, G12 0YN
Novartis Investigative Site
London, United Kingdom, EC1A 7BE
Novartis Investigative Site
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00510068     History of Changes
Other Study ID Numbers: CRAD001C2324, 2006-006819-75
Study First Received: July 31, 2007
Results First Received: November 11, 2011
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Phase III
Advanced Neuroendocrine Tumor in adults
RAD001
NET
everolimus
mTOr
islet cell
neuroendocrine

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 22, 2014