Comparing Retreatment of 177Lu-DOTATATE PRRT Versus the Usual Treatment in Patients With Metastatic Unresectable Gastroenteropancreatic Neuroendocrine Tumors, NET RETREAT Trial
NET RETREAT: A Phase II Study of 177 Lutetium-DOTATATE Retreatment vs. Everolimus or Sunitinib or Cabozantinib in Metastatic/Unresectable Gastroenteropancreatic Neuroendocrine Tumours
3 other identifiers
interventional
100
2 countries
36
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2024
Longer than P75 for phase_2
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 16, 2023
CompletedFirst Posted
Study publicly available on registry
March 17, 2023
CompletedStudy Start
First participant enrolled
January 12, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2029
May 6, 2026
April 1, 2026
5.3 years
March 16, 2023
May 5, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
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.
From randomization to any documented evidence of tumour progression or death from any cause, assessed up to 3 years
Secondary Outcomes (4)
Overall survival (OS)
From randomization to death from any cause, assessed up to 3 years
Objective response rate (ORR)
Up to 3 years
Post progression survival (PPS)
From objective progression on everolimus to objective progression or death from any cause after cross-over to receive 177Lu-DOTATATE, assessed up to 3 years
Time to second objective disease progression (PFS2)
From randomization to objective tumor progression or death from any cause after the cross-over, assessed up to 3 years
Study Arms (2)
Arm I (177Lu-DOTATATE)
EXPERIMENTALPatients 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.
Arm II (everolimus)
ACTIVE COMPARATORPatients 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
Undergo CT scan
Undergo collection of blood samples
Given PO
Given IV
Undergo MRI
Ancillary studies
Eligibility Criteria
You may qualify if:
- 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
- th 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
- +9 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (36)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
University of Rochester
Rochester, New York, 14642, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6, Canada
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
Doctor H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, A1B 3V6, Canada
London Regional Cancer Program
London, Ontario, N6A 4L6, Canada
Ottawa Hospital and Cancer Center-General Campus
Ottawa, Ontario, K1H 8L6, Canada
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Simron Singh
Canadian Cancer Trials Group
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 16, 2023
First Posted
March 17, 2023
Study Start
January 12, 2024
Primary Completion (Estimated)
April 30, 2029
Study Completion (Estimated)
April 30, 2029
Last Updated
May 6, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.