NCT06943755

Brief 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.

Trial Health

88
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
440

participants targeted

Target at P75+ for phase_2

Timeline
35mo left

Started Jul 2025

Typical duration for phase_2

Geographic Reach
14 countries

114 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress27%
Jul 2025Jun 2029

First Submitted

Initial submission to the registry

April 17, 2025

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 24, 2025

Completed
3 months until next milestone

Study Start

First participant enrolled

July 21, 2025

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2029

Last Updated

August 7, 2026

Status Verified

July 1, 2026

Enrollment Period

3.9 years

First QC Date

April 17, 2025

Last Update Submit

August 6, 2026

Conditions

Keywords

Metastatic CancerLocally Advanced CancerNeuroendocrine Tumor (NET)

Outcome Measures

Primary Outcomes (1)

  • Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)

    Up to 48 months

Secondary Outcomes (8)

  • PFS Per RECIST 1.1 as Assessed by Investigator

    Up to 48 months

  • Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR and Investigator

    Up to 48 months

  • Overall Survival (OS)

    Up to 60 months

  • Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR and Investigator

    Up to 48 months

  • Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR and Investigator

    Up to 48 months

  • +3 more secondary outcomes

Study Arms (2)

Everolimus

ACTIVE COMPARATOR

Participants will receive everolimus oral tablets once daily.

Drug: Everolimus

Zanzalintinib

EXPERIMENTAL

Participants will receive zanzalintinib oral tablets once daily.

Drug: Zanzalintinib

Interventions

Administered as specified in the treatment arm.

Also known as: XL092
Zanzalintinib

Administered as specified in the treatment arm.

Also known as: Afinitor
Everolimus

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (120)

The University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

RECRUITING

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

RECRUITING

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

RECRUITING

Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Stanford Cancer Center

Palo Alto, California, 94305, United States

RECRUITING

UCLA Health - Santa Monica Cancer Care

Santa Monica, California, 90404, United States

RECRUITING

Kaiser Permanente Medical Center

Vallejo, California, 94589, United States

RECRUITING

Georgetown University

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Mayo Clinic - Florida

Jacksonville, Florida, 32224, United States

RECRUITING

AdventHealth Orlando

Orlando, Florida, 32804, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

East Jefferson General Hospital

Metairie, Louisiana, 70006, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Cancer- Detroit

Detroit, Michigan, 48202, United States

RECRUITING

The Cancer and Hematology Centers

Grand Rapids, Michigan, 49546, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Siteman Cancer Center

St Louis, Missouri, 63110, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Icahan School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, 14642, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58102, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43221, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97210, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

RECRUITING

Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

RECRUITING

Texas Oncology- Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75264, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Monash Health

Clayton, 3168, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, 4029, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

RECRUITING

Fiona Stanley Hospital

Murdoch, 6150, Australia

RECRUITING

GenesisCare North Shore

St Leonards, 2065, Australia

RECRUITING

The Queen Elizabeth Hospital

Woodville South, 5011, Australia

RECRUITING

Medical University of Graz

Graz, 8036, Austria

RECRUITING

Paracelsus Medical University Hospital Salzburg

Salzburg, 5020, Austria

RECRUITING

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

Institut Jules Bordet

Brussels, 1070, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Cliniques Universitaires Saint-Luc (UCLouvain)

Woluwe-Saint-Lambert, 1200, Belgium

RECRUITING

Verspeeten Family Cancer Center - London Health Sciences Centre

London, N6A 5W9, Canada

RECRUITING

The Ottawa Hospital Cancer Center

Ottawa, K1H 8L6, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5, Canada

RECRUITING

Humanity and Health Clinical Trial Centre

Hong Kong, China

RECRUITING

Prince of Wales Hospital

Hong Kong, China

RECRUITING

Queen Mary Hospital

Hong Kong, China

RECRUITING

Centre Hospitalier Universitaire de Caen Normandie

Caen, 14033, France

RECRUITING

CHU Beaujon

Clichy, 92110, France

RECRUITING

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

Lille, 59037, France

RECRUITING

Hospices Civils de Lyon

Lyon, 69003, France

RECRUITING

Hôpital Timone

Marseille, 13005, France

RECRUITING

CHU de Montpellier Hôpital Saint Eloi

Montpellier, 34295, France

RECRUITING

Centre Hospitalier Universitaire Nantes

Nantes, 44093, France

RECRUITING

Centre Eugéne Marquis

Rennes, 35042, France

RECRUITING

CHRU Strasbourg Hôpital Hautepierre

Strasbourg, 67200, France

RECRUITING

Centre Hospitalier Universitaire (CHU) Toulouse

Toulouse, 31059, France

RECRUITING

Gustave Roussy

Villejuif, 94800, France

RECRUITING

Evangelische Lungenklinik

Berlin, 13125, Germany

RECRUITING

Universitätsklinik Erlangen

Erlangen, 91054, Germany

RECRUITING

Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg

Marburg, 35043, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

University Hospital Würzburg

Würzburg, 97080, Germany

RECRUITING

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

Bologna, 40138, Italy

RECRUITING

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

Meldola, 47014, Italy

RECRUITING

Humanitas Mirasole S.p.A.

Milan, 20089, Italy

RECRUITING

Instituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Istituto Nazionale Tumori IRCCS - Fondazione Pascale

Naples, 80131, Italy

RECRUITING

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano to, 10043, Italy

RECRUITING

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90127, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Policlinico Umberto I

Roma, 00161, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Sant'Andrea

Roma, 00189, Italy

RECRUITING

Het Netherlands Kanker Institut (NKI)/ Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

RECRUITING

Amsterdam UMC

Amsterdam, 1081 HV, Netherlands

RECRUITING

Maastricht Universitair Medisch Centrum

Maastricht, 6229 HX, Netherlands

RECRUITING

Maxima Medisch Centrum

Veldhoven, 5504 DB, Netherlands

RECRUITING

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

Gliwice, 44-102, Poland

RECRUITING

Śląskiego Uniwersytet Medyczny w Katowicach

Katowice, 40-514, Poland

RECRUITING

Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie

Krakow, 30-688, Poland

RECRUITING

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

Warsaw, 02-034, Poland

RECRUITING

FutureMeds Wrocław

Wroclaw, 53-673, Poland

RECRUITING

Pan American Center for Oncology Trials, LLC

San Juan, 00909, Puerto Rico

RECRUITING

FDI Clinical Resesarch

San Juan, 00927, Puerto Rico

WITHDRAWN

Korea University Anam Hospital

Seoul, 2841, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 3080, South Korea

RECRUITING

Severence Hospital, Yonsei University Health System

Seoul, 3722, South Korea

RECRUITING

Asan Medical Center

Seoul, 5505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 6351, South Korea

RECRUITING

Hospital Universitario Vall D'Hebron

Barcelona, 8029, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital General Universitario J.M Morales Meseguer

Murcia, 30008, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

RECRUITING

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

RECRUITING

Hospital Universitario Vigen Del Rocío

Seville, 41013, Spain

RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

RECRUITING

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2GW, United Kingdom

RECRUITING

Velindre Cancer Center

Cardiff, CF14 2TL, United Kingdom

RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, G12 0YN, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre

Liverpool, L7 8YA, United Kingdom

RECRUITING

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE, United Kingdom

RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2SJ, United Kingdom

RECRUITING

Swansea Bay University Health Board

Swansea, SA2 8QA, United Kingdom

RECRUITING

MeSH Terms

Conditions

Adenoma, Islet CellNeoplasm MetastasisNeuroendocrine Tumors

Interventions

Everolimus

Condition Hierarchy (Ancestors)

AdenomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsPancreatic NeoplasmsDigestive System NeoplasmsNeoplasms by SiteEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and SymptomsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic Chemicals

Study Officials

  • Medical Director

    Exelixis

    STUDY DIRECTOR

Central Study Contacts

Backup or International

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 17, 2025

First Posted

April 24, 2025

Study Start

July 21, 2025

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

June 30, 2029

Last Updated

August 7, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will not share

Locations