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

NCT ID: NCT00510068

Last Updated: 2015-07-01

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

410 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Study Completion Date

2014-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced Neuroendocrine Tumors of Pancreatic Origin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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).

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

A 10-mg dose of everolimus was given by continuous oral daily dosing of two 5-mg tablets.

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).

Group Type PLACEBO_COMPARATOR

Everolimus Placebo

Intervention Type DRUG

a 10-mg dose of matching placebo to Everolimus was given by continuous oral daily dosing of two 5-mg tablets.

Interventions

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Everolimus

A 10-mg dose of everolimus was given by continuous oral daily dosing of two 5-mg tablets.

Intervention Type DRUG

Everolimus Placebo

a 10-mg dose of matching placebo to Everolimus was given by continuous oral daily dosing of two 5-mg tablets.

Intervention Type DRUG

Other Intervention Names

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RAD001

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of South Alabama / Mitchell Cancer Institute Deptof Mitchell Cancer Inst(2)

Mobile, Alabama, United States

Site Status

Pacific Cancer Medical Center, Inc.

Anaheim, California, United States

Site Status

Cedars Sinai Medical Center SC-2

Los Angeles, California, United States

Site Status

University of California at Los Angeles UCLA (3)

Los Angeles, California, United States

Site Status

University of California San Francisco Dept. of UCSF Comp. Cancer

San Francisco, California, United States

Site Status

Kaiser Permanente Northwest Franklin Medical Offices

Denver, Colorado, United States

Site Status

H. Lee Moffitt Cancer Center & Research Institute Malignant Hematology Clinic

Tampa, Florida, United States

Site Status

Indiana University Health Goshen Center for Cancer Dept. of Indiana Univ. Cancer

Indianapolis, Indiana, United States

Site Status

University of Iowa Medical Center Dept. of Iowa Medical Center

Iowa City, Iowa, United States

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University of Louisville / James Graham Brown Cancer Center SC

Louisville, Kentucky, United States

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LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Dept. of Neuroendocrine Clinic

New Orleans, Louisiana, United States

Site Status

Boston Medical Center BMC

Boston, Massachusetts, United States

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Wayne State University/Karmanos Cancer Institute Dept.of KarmanosCancerInst (4)

Detroit, Michigan, United States

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Mayo Clinic - Rochester

Rochester, Minnesota, United States

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Littleton Regional Hospital Dept. of Hematology/Oncology

Littleton, New Hampshire, United States

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Columbia University Medical Center- New York Presbyterian Dept. of Columbia Med. Center

New York, New York, United States

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Levine Cancer Institute

Charlotte, North Carolina, United States

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Ohio State Comprehensive Cancer Center/James Cancer Hospital Dept. of OHSU Medical Center

Columbus, Ohio, United States

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Oregon Health & Science University Dept. of OHSU (3)

Portland, Oregon, United States

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St. Luke's Hospital and Health Network St. Luke's Cancer Network

Bethlehem, Pennsylvania, United States

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Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

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University of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

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The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

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University of Texas/MD Anderson Cancer Center Dept of MD Anderson CancerCent

Houston, Texas, United States

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Novartis Investigative Site

Brussels, , Belgium

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Brussels, , Belgium

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Leuven, , Belgium

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Fortaleza, Ceará, Brazil

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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London, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Strasbourg, France, France

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Besançon, , France

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Clichy, , France

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Dijon, , France

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Lille, , France

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Lyon, , France

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Marseille, , France

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Montpellier, , France

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Paris, , France

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Paris, , France

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Reims, , France

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Toulouse, , France

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Villejuif, , France

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Mainz, Germany, Germany

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Bad Berka, , Germany

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Berlin, , Germany

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Marburg, , Germany

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München, , Germany

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Athens, GR, Greece

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Athens, , Greece

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Bologna, BO, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Modena, MO, Italy

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Pisa, PI, Italy

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Kashiwa, Chiba, Japan

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Fukuoka, Fukuoka, Japan

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Chuo-ku, Tokyo, Japan

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Groningen, , Netherlands

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Martin, Slovak Republic, Slovakia

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Seoul, Korea, South Korea

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Seoul, Korea, South Korea

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Seoul, Korea, South Korea

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Seoul, , South Korea

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Barcelona, Catalonia, Spain

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L'Hospitalet de Llobregat, Catalonia, Spain

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Uppsala, , Sweden

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Zurich, Switzerland, Switzerland

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Taipei, Taiwan, Taiwan

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Taipei, Taiwan, ROC, Taiwan

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Kaohsiung City, , Taiwan

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Lin-Ko, , Taiwan

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Bangkok, , Thailand

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Songkhla, , Thailand

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Withington, Greater Manchester, United Kingdom

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Glasgow, , United Kingdom

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London, , United Kingdom

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Novartis Investigative Site

London, , United Kingdom

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Countries

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United States Belgium Brazil Canada France Germany Greece Italy Japan Netherlands Slovakia South Korea Spain Sweden Switzerland Taiwan Thailand United Kingdom

References

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Chan DL, Yao JC, Carnaghi C, Buzzoni R, Herbst F, Ridolfi A, Strosberg J, Kulke MH, Pavel M, Singh S. Markers of Systemic Inflammation in Neuroendocrine Tumors: A Pooled Analysis of the RADIANT-3 and RADIANT-4 Studies. Pancreas. 2021 Feb 1;50(2):130-137. doi: 10.1097/MPA.0000000000001745.

Reference Type DERIVED
PMID: 33560090 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28113028 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27621394 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25479584 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21306238 (View on PubMed)

Other Identifiers

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2006-006819-75

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001C2324

Identifier Type: -

Identifier Source: org_study_id

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