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

NCT00510068 | Completed Phase 3 Results DMC

• 2 other identifiers: CRAD001C23242006-006819-75
• Study Type: interventional
• Target: 410
• Locations: 18 countries
• Sites: 82

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.

Conditions

Advanced Neuroendocrine Tumors of Pancreatic Origin

Keywords

Phase III; Advanced Neuroendocrine Tumor in adults; RAD001; NET; everolimus; mTOr; islet cell; neuroendocrine

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (17)

• Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response})

  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

• Overall Survival

  Baseline, to death- no time limit

• 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%

  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

• Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response

  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

• Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response

  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

Study Arms (2)

Everolimus 10 mg/day

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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: Everolimus Placebo

Interventions

Everolimus DRUG

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

Also known as: RAD001

Everolimus 10 mg/day

Everolimus Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (82)

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

Mobile, Alabama, 36688, United States

Location

Pacific Cancer Medical Center, Inc.

Anaheim, California, 92801, United States

Location

Cedars Sinai Medical Center SC-2

Los Angeles, California, 90048, United States

Location

University of California at Los Angeles UCLA (3)

Los Angeles, California, 90095, United States

Location

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

San Francisco, California, 94143-0128, United States

Location

Kaiser Permanente Northwest Franklin Medical Offices

Denver, Colorado, United States

Location

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

Tampa, Florida, 33612, United States

Location

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

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Medical Center Dept. of Iowa Medical Center

Iowa City, Iowa, 52242, United States

Location

University of Louisville / James Graham Brown Cancer Center SC

Louisville, Kentucky, 40202, United States

Location

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

New Orleans, Louisiana, 70115, United States

Location

Boston Medical Center BMC

Boston, Massachusetts, 02118, United States

Location

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

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Littleton Regional Hospital Dept. of Hematology/Oncology

Littleton, New Hampshire, 03561, United States

Location

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

New York, New York, 10032, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

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

Columbus, Ohio, 43210, United States

Location

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

Portland, Oregon, 97239, United States

Location

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

Bethlehem, Pennsylvania, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

University of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

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

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Brussels, 1070, Belgium

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Fortaleza, Ceará, 60430-370, Brazil

Location

Novartis Investigative Site

Calgary, Alberta, T2N 4N2, Canada

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Novartis Investigative Site

London, Ontario, N6A 4L6, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H1T 2M4, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3A 1A1, Canada

Location

Novartis Investigative Site

Strasbourg, France, 67098, France

Location

Novartis Investigative Site

Besançon, 25030, France

Location

Novartis Investigative Site

Clichy, 92110, France

Location

Novartis Investigative Site

Dijon, 21079, France

Location

Novartis Investigative Site

Lille, 59020, France

Location

Novartis Investigative Site

Lyon, 69437, France

Location

Novartis Investigative Site

Marseille, 13385, France

Location

Novartis Investigative Site

Montpellier, 34298, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Paris, 75651, France

Location

Novartis Investigative Site

Reims, 51092, France

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Mainz, Germany, 55131, Germany

Location

Novartis Investigative Site

Bad Berka, 99438, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Marburg, 35033, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Athens, GR, 115 27, Greece

Location

Novartis Investigative Site

Athens, GR-115 22, Greece

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Modena, MO, 41100, Italy

Location

Novartis Investigative Site

Pisa, PI, 56124, Italy

Location

Novartis Investigative Site

Kashiwa, Chiba, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Novartis Investigative Site

Chuo-ku, Tokyo, Japan

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Martin, Slovak Republic, 036 59, Slovakia

Location

Novartis Investigative Site

Seoul, Korea, 110 744, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 120-752, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 135-710, South Korea

Location

Novartis Investigative Site

Seoul, 738-736, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Uppsala, SE-751 85, Sweden

Location

Novartis Investigative Site

Zurich, Switzerland, 8091, Switzerland

Location

Novartis Investigative Site

Taipei, Taiwan, 10002, Taiwan

Location

Novartis Investigative Site

Taipei, Taiwan, ROC, 112, Taiwan

Location

Novartis Investigative Site

Kaohsiung City, 807, Taiwan

Location

Novartis Investigative Site

Lin-Ko, 33305, Taiwan

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Novartis Investigative Site

Songkhla, 90110, Thailand

Location

Novartis Investigative Site

Withington, Greater Manchester, M20 4BX, United Kingdom

Location

Novartis Investigative Site

Glasgow, G12 0YN, United Kingdom

Location

Novartis Investigative Site

London, EC1A 7BE, United Kingdom

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 33560090 DERIVED

• 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.

  PMID: 28113028 DERIVED

• 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.

  PMID: 27621394 DERIVED

• 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.

  PMID: 25479584 DERIVED

• 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.

  PMID: 21306238 DERIVED

MeSH Terms

Interventions

Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2007
• First Posted: August 1, 2007
• Study Start: July 1, 2007
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2014
• Last Updated: July 1, 2015
• Results First Posted: December 15, 2011

Record last verified: 2015-06

Locations

BR (1); NL (1); US (24); CH (1); GB (4); BE (3); KR (4); CA (5); FR (13); GR (2); ES (2); TW (4); TH (2); DE (5); IT (6); SE (1); JP (3); SL (1)