NET RETREAT Trial: Comparing 177Lu-DOTATATE Retreatment for Neuroendocrine Tumors
This study, called the NET RETREAT trial, is comparing two ways to treat advanced gastroenteropancreatic neuroendocrine tumors (GEPNETs) that have spread and cannot be removed by surgery. You might be eligible if you have GEPNETs that are Grade 1 or 2, have spread, and have already been treated with 177Lu-DOTATATE (a type of radiation therapy). The study is looking at whether retreating with 177Lu-DOTATATE is better than the usual treatments, which include medications like everolimus, cabozantinib, or sunitinib. Researchers will measure how long patients live without their cancer getting worse (progression-free survival) for up to 3 years. The study aims to enroll 100 participants.
- Study design
- This is an interventional study comparing two treatment approaches. It aims to enroll 100 participants.
- What's involved
- You would undergo blood sample collection and CT scans. The specific frequency and duration of these procedures are not detailed.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your progression-free survival will be assessed for up to 3 years after randomization.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05773274
Comparing Retreatment of 177Lu-DOTATATE PRRT Versus the Usual Treatment in Patients With Metastatic Unresectable Gastroenteropancreatic Neuroendocrine Tumors, NET RETREAT Trial
Recruiting
PHASE2Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~100 participants
Updated 2026-08-31 on ClinicalTrials.gov
What's tested:Biospecimen CollectionCabozantinibComputed TomographyEverolimusLutetium Lu 177 DotatateMagnetic Resonance Imaging
At a glance
Recruiting sites
37 of 40 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Progression-free survival (PFS)
Measured over From randomization to any documented evidence of tumour progression or death from any cause, assessed up to 3 years
Conditions
Where it's being run
40 sites across 17 statesFlorida8
Illinois8
Iowa6
Arizona3
Ontario3
Alabama1
Colorado1
Kentucky1
Study leadership
- Simron Singh · PRINCIPAL_INVESTIGATOR · Canadian Cancer Trials Group
Who to contact
Site Public Contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
What this trial measures
- Progression-free survival (PFS)From randomization to any documented evidence of tumour progression or death from any cause, assessed up to 3 years
The PFS of patients of both treatment groups will be described by Kaplan-Meier method and the median PFS will be estimated using the same method. A one-sided stratified log-rank test adjusting for the stratification factor at randomization will be the primary method to compare the difference in PFS between the experimental and control treatments, at the 5% level. A stratified Cox model adjusting for duration of durable response to the initial peptide receptor radionuclide therapy (durable response \>= 24 months versus \[vs.\] \< 24 months) at randomization and with one single treatment covariate will be used to estimate the hazard ratio and associated one-sided 95% confidence interval. Sensitivity analysis adjusting for all three stratification factors at randomization will also be performed.