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NCT06943755PHASE2, PHASE3Recruiting

Zanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors

Exelixis

Start Date

7/21/2025

Completion Date

6/30/2029

Summary

The primary purpose of this study is to assess the effectiveness of zanzalintinib compared to everolimus in participants with previously treated, unresectable, locally advanced or metastatic neuroendocrine tumors.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: * Histologically confirmed, locally advanced/unresectable or metastatic, well-differentiated Grade 1, 2, or 3 NETs of pancreatic origin or extra-pancreatic origin. * Allowed prior lines of therapy, based on the site of NET and functional status. * Documented radiographic disease progression per RECIST 1.1, as assessed by the Investigator based on imaging assessments (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) within 12 months before randomization. * Measurable disease according to RECIST 1.1 as determined by the Investigator. * Archival tumor tissue is required, if available. If archival tumor tissue is not available, a fresh biopsy may be submitted if it can be safely and feasibly obtained. Every attempt should be made to provide tumor tissue. Key Exclusion Criteria: * Histologically confirmed neuroendocrine carcinomas (including small cell lung cancer), medullary thyroid cancer, pheochromocytoma, paraganglioma, Merkel cell carcinoma, and mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN). * Prior treatment with a vascular endothelial growth factor receptor (VEGFR) -targeting tyrosine kinase inhibitor or a mammalian target of rapamycin (mTOR) inhibitor. * Systemic chemotherapy and any liver-directed or other ablative therapy within 4 weeks before randomization. * Systemic radionuclide therapy within 6 weeks before randomization. * Radiation therapy for bone metastases within 2 weeks, any other radiation therapy, except as indicated above, within 4 weeks before randomization. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Interventions

DRUG

Zanzalintinib

DRUG

Everolimus

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Conditions

Pancreatic Neuroendocrine Tumor (pNET)Extra-Pancreatic Neuroendocrine Tumor (epNET)

Locations

The University of Alabama at Birmingham

Birmingham, Alabama 35294

United States

Mayo Clinic Hospital

Phoenix, Arizona 85054

United States

The University of Arizona Cancer Center

Tucson, Arizona 85724

United States

Cedars-Sinai Medical Center

Beverly Hills, California 90211

United States

Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Stanford Cancer Center

Palo Alto, California 94305

United States

UCLA Health - Santa Monica Cancer Care

Santa Monica, California 90404

United States

Kaiser Permanente Medical Center

Vallejo, California 94589

United States

Georgetown University

Washington D.C., District of Columbia 20007

United States

Mayo Clinic - Florida

Jacksonville, Florida 32224

United States

AdventHealth Orlando

Orlando, Florida 32804

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

University of Kentucky Markey Cancer Center

Lexington, Kentucky 40536

United States

East Jefferson General Hospital

Metairie, Louisiana 70006

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Henry Ford Cancer- Detroit

Detroit, Michigan 48202

United States

The Cancer and Hematology Centers

Grand Rapids, Michigan 49546

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Siteman Cancer Center

St Louis, Missouri 63110

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico 87131

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Icahan School of Medicine at Mount Sinai

New York, New York 10029

United States

University of Rochester Medical Center

Rochester, New York 14642

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota 58102

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43221

United States

Oregon Health and Science University

Portland, Oregon 97210

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

University of Tennessee Medical Center

Knoxville, Tennessee 37920

United States

Henry-Joyce Cancer Clinic

Nashville, Tennessee 37232

United States

Texas Oncology- Baylor Charles A. Sammons Cancer Center

Dallas, Texas 75264

United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah 84112

United States

University of Virginia

Charlottesville, Virginia 22903

United States

Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia 22031

United States

Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Monash Health

Clayton, 3168

Australia

Royal Brisbane and Women's Hospital

Herston, 4029

Australia

Peter MacCallum Cancer Centre

Melbourne, 3000

Australia

Fiona Stanley Hospital

Murdoch, 6150

Australia

GenesisCare North Shore

St Leonards, 2065

Australia

The Queen Elizabeth Hospital

Woodville South, 5011

Australia

Medical University of Graz

Graz, 8036

Austria

Paracelsus Medical University Hospital Salzburg

Salzburg, 5020

Austria

Medical University of Vienna

Vienna, 1090

Austria

Institut Jules Bordet

Brussels, 1070

Belgium

UZ Leuven

Leuven, 3000

Belgium

Cliniques Universitaires Saint-Luc (UCLouvain)

Woluwe-Saint-Lambert, 1200

Belgium

Verspeeten Family Cancer Center - London Health Sciences Centre

London, N6A 5W9

Canada

The Ottawa Hospital Cancer Center

Ottawa, K1H 8L6

Canada

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5

Canada

Humanity and Health Clinical Trial Centre

Hong Kong,

China

Prince of Wales Hospital

Hong Kong,

China

Queen Mary Hospital

Hong Kong,

China

Centre Hospitalier Universitaire de Caen Normandie

Caen, 14033

France

CHU Beaujon

Clichy, 92110

France

Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Claude Huriez

Lille, 59037

France

Hospices Civils de Lyon

Lyon, 69003

France

Hôpital Timone

Marseille, 13005

France

CHU de Montpellier Hôpital Saint Eloi

Montpellier, 34295

France

Centre Hospitalier Universitaire Nantes

Nantes, 44093

France

Centre Eugéne Marquis

Rennes, 35042

France

CHRU Strasbourg Hôpital Hautepierre

Strasbourg, 67200

France

Centre Hospitalier Universitaire (CHU) Toulouse

Toulouse, 31059

France

Gustave Roussy

Villejuif, 94800

France

Evangelische Lungenklinik

Berlin, 13125

Germany

Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg

Marburg, 35043

Germany

Universitätsklinikum Tübingen

Tübingen, 72076

Germany

University Hospital Würzburg

Würzburg, 97080

Germany

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Bologna, 40138

Italy

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST s.r.l.

Meldola, 47014

Italy

Instituto Europeo di Oncologia

Milan, 20141

Italy

Istituto Nazionale Tumori IRCCS - Fondazione Pascale

Naples, 80131

Italy

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano to, 10043

Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90127

Italy

Azienda Ospedaliero-Universitaria Policlinico Umberto I

Roma, 00161

Italy

Het Netherlands Kanker Institut (NKI)/ Antoni van Leeuwenhoek

Amsterdam, 1066 CX

Netherlands

Amsterdam UMC

Amsterdam, 1081 HV

Netherlands

Maastricht Universitair Medisch Centrum

Maastricht, 6229 HX

Netherlands

Maxima Medisch Centrum

Veldhoven, 5504 DB

Netherlands

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy, Oddział w Gliwicach

Gliwice, 44-102

Poland

Śląskiego Uniwersytet Medyczny w Katowicach

Katowice, 40-514

Poland

Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie

Krakow, 30-688

Poland

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, 02-034

Poland

FutureMeds Wrocław

Wroclaw, 53-673

Poland

Pan American Center for Oncology Trials, LLC

San Juan, 00909

Puerto Rico

FDI Clinical Resesarch

San Juan, 00927

Puerto Rico

Korea University Anam Hospital

Seoul, 2841

South Korea

Seoul National University Hospital

Seoul, 3080

South Korea

Severence Hospital, Yonsei University Health System

Seoul, 3722

South Korea

Asan Medical Center

Seoul, 5505

South Korea

Samsung Medical Center

Seoul, 6351

South Korea

Hospital Universitario Vall D'Hebron

Barcelona, 8029

Spain

Hospital General Universitario Gregorio Marañón

Madrid, 28007

Spain

Hospital Universitario Ramón y Cajal

Madrid, 28034

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario La Paz

Madrid, 28046

Spain

Hospital General Universitario J.M Morales Meseguer

Murcia, 30008

Spain

Hospital Universitario Central de Asturias

Oviedo, 33011

Spain

Hospital Universitario Marqués de Valdecilla

Santander, 39008

Spain

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, 15706

Spain

Hospital Universitario Vigen Del Rocío

Seville, 41013

Spain

Hospital Universitario y Politécnico La Fe

Valencia, 46026

Spain

Hospital Universitario Miguel Servet

Zaragoza, 50009

Spain

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2GW

United Kingdom

Velindre Cancer Center

Cardiff, CF14 2TL

United Kingdom

NHS Greater Glasgow and Clyde

Glasgow, G12 0YN

United Kingdom

The Clatterbridge Cancer Centre

Liverpool, L7 8YA

United Kingdom

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT

United Kingdom

King's College Hospital NHS Foundation Trust

London, SE5 9RS

United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE

United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2SJ

United Kingdom

Swansea Bay University Health Board

Swansea, SA2 8QA

United Kingdom