Recruiting
Phase 2

177Lu-DOTATATE vs. Everolimus

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05773274

Conditions

Metastatic Digestive System Neuroendocrine Tumor G1

Metastatic Digestive System Neuroendocrine Tumor G2

Unresectable Digestive System Neuroendocrine Tumor G1

Unresectable Digestive System Neuroendocrine Tumor G2

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Cabozantinib

Computed Tomography

Everolimus

Lutetium Lu 177 Dotatate

Study Details

Brief summary:

This phase II trial compares the effect of retreatment with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) to the usual approach of treatment with everolimus, sunitinib, or cabozantinib in patients who have previously received 177Lu-DOTATATE for gastroenteropancreatic neuroendocrine tumor (GEPNET) that has spread from where it first started (primary site) to other places in the body (metastatic) and that cannot be removed by surgery (unresectable). PRRT is a type of radiation therapy for which a radioactive chemical is linked to a peptide (small protein) that targets tumor cells. When this radioactive peptide is injected into the body, it binds to a specific receptor found on some tumor cells. The radioactive peptide builds up in these cells and helps kill the tumor cells without harming normal cells. In this trial 177Lu-DOTATATE is used for PRRT. 177Lu-DOTATATE PRRT may increase the length of time until worsening of the GEPNET compared to the usual approach. Everolimus is in a class of medications called kinase inhibitors. It is also a type of angiogenesis inhibitor. Everolimus works by stopping tumor cells from reproducing and by decreasing blood supply to the tumor cells. Sunitinib and cabozantinib, block certain proteins, which may help keep tumor cells from growing. They may also prevent the growth of new blood vessels that tumors need to grow. Sunitinib malate is a type of tyrosine kinase inhibitor and a type of antiangiogenesis agent. Retreating with 177Lu-DOTATATE may work better than everolimus, sunitinib or cabozantinib in shrinking or stabilizing tumors in patients with metastatic and unresectable GEPNET who were previously treated with 177Lu-DOTATATE.

Conditions

Metastatic Digestive System Neuroendocrine Tumor G1

Metastatic Digestive System Neuroendocrine Tumor G2

Unresectable Digestive System Neuroendocrine Tumor G1

Unresectable Digestive System Neuroendocrine Tumor G2

Study ID

NCT05773274

Start date

Jan 12, 2024

Status verified date

May, 2026

Completion date

Apr 30, 2029

Anticipated

Primary completion date

Apr 30, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients must be at least >= 18 years of age
  • Metastatic, histologically confirmed grade 1 or 2 well-differentiated gastroenteropancreatic neuroendocrine tumours, including NETs of unknown primary thought to be of gastroenterogancreatic origin, with positive Gallium-68 DOTATATE scan, Copper-64 DOTATATE scan or octreotide scan within the last 12 months is recommended but within the last 36 months is allowed. Lesions on Gallium-68 or Copper-64 DOTATATE scan or octreotide scan will be considered positive if the maximum standardized uptake value (SUVmax) of target lesion is > SUV mean of normal liver parenchyma

  • 7th Edition of the TNM Classification of Malignant Tumours
  • Have received 3 or 4 cycles of PRRT using 177Lu-DOTATATE or a cumulative exposure of 22,200 MBq (600mCi) or 29,600 MBq (800 mCi) within +/- 10% variation within a 52-week period. No previous targeted alpha therapy is permitted
  • Have had radiological progression per RECIST 1.1 after prior PRRT treatment and no sooner than 12 months from last scan performed post completion of initial PRRT where either stable disease, partial response, or complete response has been maintained throughout. Patients may have received previous systemic anti-cancer therapy subsequently, as long as they had benefited from initial PRRT for at least 12 months and have had confirmed progression per RECIST 1.1 on the intervening systemic anti-cancer therapy. Somatostatin analogues (SSA) administered for functional control are not considered an intervening systemic anti-cancer therapy. If intervening systemic anti-cancer therapy included a vascular endothelial growth factor (VEGF)-inhibitor, sunitinib can not be selected as standard of care on Arm 2. If intervening systemic anti-cancer therapy included an mammalian target of rapamycin (mTOR)-inhibitor, then everolimus can not be selected as the standard of care on Arm 2. If the intervening therapy is an alkylating agent, exposure of alkylating agent cannot exceed 12 months. The 12-month limit will also be applied to pre PRRT alkylator use as well
  • Patients may have received previous ablative therapy or bland embolization as liver directed therapy however this must not have been received within 12 weeks from randomization date. Previous chemo and radio embolization are not permitted. Any lesion treated with an ablative technique as well as lesions in the lobe(s) of the liver treated with embolization shall not be included in target lesion assessment unless they have since progressed
  • No ongoing toxicity from prior PRRT that is grade 3 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin >= 80 g/L (>= 8.0 g/dL) (measured within 28 days prior to enrollment)
  • Absolute neutrophil count >= 1.0 x 10\^9/L (>= 1000/mm\^3) (measured within 28 days prior to enrollment)
  • Platelets >= 80 x 10\^9/L (>= 80 x 10\^3/mm\^3) (measured within 28 days prior to enrollment)
  • Total bilirubin < 1.5 x upper limit of normal (ULN) (upper limit of normal) (measured within 28 days prior to enrollment)

  • If confirmed Gilbert's, eligible providing =< 3.0 x ULN
  • Creatinine clearance > 50 mL/min (measured within 28 days prior to enrollment)

  • Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft and Gault equation
  • Prior or current use of somatostatin analogues is allowed for carcinoid syndrome control or in PRRT re-treatment patient population (Arm 1). Patients randomized to Arm 2 and receiving everolimus or sunitinib (pancreatic NET patients only) or cabozantinib (US patients only) will not be allowed to continue somatostatin analogues unless they have functional syndrome
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
  • Males and females of reproductive potential must have agreed to use a highly effective contraceptive method during protocol treatment and for 7 months after the last dose of protocol treatment for females and 4 months after the last dose of protocol treatment for males. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. Men should avoid fathering a child for 4 months after the last dose of 177Lu-DOTATATE

  • Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation; this may include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of human chorionic gonadotropin (hCG), as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy
  • Patients must be accessible for treatment, response assessment, and follow up. Patients enrolled on this trial must be treated and followed at the participating center. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up

  • Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial
  • Patient must have access to everolimus or sunitinib (pancreatic NET patients only) or cabozantinib (US patients only). In the event that site/investigator is unable to provide access to the drug, patient will not be eligible for this trial
  • Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Exclusion Criteria:

  • Major surgical procedures within 6 weeks from randomization date
  • Known brain metastases, unless these metastases have been treated, stabilized and off steroids for at least 4 weeks prior to enrollment in the study. Patients with a history of brain metastases must have a head CT and/or MRI with contrast to document stable disease prior to enrollment in the study
  • Uncontrolled congestive heart failure no worse than New York Heart Association Class (NYHA) IIB
  • Inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents
  • Patients with any other significant medical or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study
  • Pregnant women are excluded from this study because 177Lu-DOTATATE is a peptide receptor radionuclide therapy with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 177Lu-DOTATATE, breastfeeding should be discontinued if the mother is treated with everolimus or sunitinib or cabozantinib (US patients only) and for 2.5 months following the last treatment with 177Lu-DOTATATE

Study Design

Enrollment

100 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (177Lu-DOTATATE)

Patients receive 177Lu-DOTATATE IV over 30 minutes Q8W. Treatment repeats for two cycles in the absence of disease progression or unacceptable toxicities. Patients also undergo CT scan and/or MRI and collection of blood samples while on study.

active comparator: Arm II (everolimus)

Patients receive everolimus PO QD, sunitinib PO QD or cabozantinib PO QD. Treatment continues in the absence of disease progression or unacceptable toxicities. Patients whose cancer worsens may cross over to ARM I. Patients also undergo CT scan and/or MRI and collection of blood samples while on study.

Interventions

Biospecimen Collection

Undergo collection of blood samples

Cabozantinib

Given PO

Computed Tomography

Undergo CT scan

Everolimus

Given PO

Lutetium Lu 177 Dotatate

Given IV

Magnetic Resonance Imaging

Undergo MRI

Quality-of-Life Assessment

Ancillary studies

Questionnaire Administration

Ancillary studies

Sunitinib

Given PO

Primary outcome measure

  • Progression-free survival (PFS) [ Time Frame: From randomization to any documented evidence of tumour progression or death from any cause, assessed up to 3 years ]

Central Contacts and Locations

Locations

University of Alabama at Birmingham Cancer Center

Recruiting

Birmingham, Alabama, United States, 35233

Contacts

Site Public Contact

gingerreeves@uabmc.edu

Principal Investigator:

Garima Gupta

Mayo Clinic Hospital in Arizona

Recruiting

Phoenix, Arizona, United States, 85054

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Patrick W. McGarrah

Banner University Medical Center - Tucson

Recruiting

Tucson, Arizona, United States, 85719

Contacts

Site Public Contact

UACC-IIT@uacc.arizona.edu

Principal Investigator:

Rachna T. Shroff

University of Arizona Cancer Center-North Campus

Recruiting

Tucson, Arizona, United States, 85719

Contacts

Site Public Contact

UACC-IIT@uacc.arizona.edu

Principal Investigator:

Rachna T. Shroff

UCHealth University of Colorado Hospital

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Site Public Contact

720-848-0650

Principal Investigator:

Emily Baiyee-Toegel

UM Sylvester Comprehensive Cancer Center at Aventura

Recruiting

Aventura, Florida, United States, 33180

Contacts

Site Public Contact

954-461-2180

Principal Investigator:

Gretel Terrero

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Gretel Terrero

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Gretel Terrero

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224-9980

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Patrick W. McGarrah

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Gretel Terrero

UM Sylvester Comprehensive Cancer Center at Kendall

Recruiting

Miami, Florida, United States, 33176

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Gretel Terrero

University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

Recruiting

North Miami, Florida, United States, 33181

Contacts

Site Public Contact

kginnity@med.miami.edu

Principal Investigator:

Gretel Terrero

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Gretel Terrero

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Site Public Contact

312-695-1301cancer@northwestern.edu

Principal Investigator:

Al B. Benson

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Chih-Yi Liao

Northwestern Medicine Cancer Center Kishwaukee

Recruiting

DeKalb, Illinois, United States, 60115

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Al B. Benson

Northwestern Medicine Cancer Center Delnor

Recruiting

Geneva, Illinois, United States, 60134

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Al B. Benson

UC Comprehensive Cancer Center at Silver Cross

Recruiting

New Lenox, Illinois, United States, 60451

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Chih-Yi Liao

Northwestern Medicine Oak Brook

Recruiting

Oak Brook, Illinois, United States, 60523

Contacts

Site Public Contact

nctnprogram_rhlccc@northwestern.edu

Principal Investigator:

Al B. Benson

University of Chicago Medicine-Orland Park

Recruiting

Orland Park, Illinois, United States, 60462

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Chih-Yi Liao

Northwestern Medicine Cancer Center Warrenville

Recruiting

Warrenville, Illinois, United States, 60555

Contacts

Site Public Contact

630-352-5360Donald.Smith3@nm.org

Principal Investigator:

Al B. Benson

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Recruiting

Ankeny, Iowa, United States, 50023

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Recruiting

Clive, Iowa, United States, 50325

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

Iowa Methodist Medical Center

Recruiting

Des Moines, Iowa, United States, 50309

Contacts

Site Public Contact

515-241-6727

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Recruiting

Des Moines, Iowa, United States, 50309

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - Laurel Clinic

Recruiting

Des Moines, Iowa, United States, 50314

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - Waukee Clinic

Recruiting

Waukee, Iowa, United States, 50263

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Patrick W. McGarrah

University of New Mexico Cancer Center

Recruiting

Albuquerque, New Mexico, United States, 87106

Contacts

Site Public Contact

505-925-0348HSC-ClinicalTrialInfo@salud.unm.edu

Principal Investigator:

Bernard Tawfik

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

Bhavana Konda

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100cancerinfo@hci.utah.edu

Principal Investigator:

Heloisa P. Soares

BCCA-Vancouver Cancer Centre

Recruiting

Vancouver, British Columbia, Canada, V5Z 4E6

Contacts

Site Public Contact

888-939-3333

Principal Investigator:

Jonathan M. Loree

Doctor H. Bliss Murphy Cancer Centre

Recruiting

St. John's, Newfoundland and Labrador, Canada, A1B 3V6

Contacts

Site Public Contact

709-777-7589

Principal Investigator:

Renee Lester

London Regional Cancer Program

Recruiting

London, Ontario, Canada, N6A 4L6

Contacts

Site Public Contact

519-685-8600

Principal Investigator:

David Laidley

Ottawa Hospital and Cancer Center-General Campus

Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contacts

Site Public Contact

613-761-4395

Principal Investigator:

Timothy R. Asmis

Odette Cancer Centre- Sunnybrook Health Sciences Centre

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contacts

Site Public Contact

416-480-5000

Principal Investigator:

Simron Singh

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 3, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-03.