Trial Title:
Comparing Retreatment of 177Lu-DOTATATE PRRT Versus Everolimus in Patients With Metastatic Unresectable Midgut Neuroendocrine Tumors, NET RETREAT Trial
NCT ID:
NCT05773274
Condition:
Metastatic Midgut Neuroendocrine Tumor
Metastatic Midgut Neuroendocrine Tumor G1
Metastatic Midgut Neuroendocrine Tumor G2
Unresectable Midgut Neuroendocrine Tumor
Conditions: Official terms:
Neoplasms
Neuroendocrine Tumors
Everolimus
Lutetium Lu 177 dotatate
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Arm I (177Lu-DOTATATE)
Arm group label:
Arm II (everolimus)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Arm I (177Lu-DOTATATE)
Arm group label:
Arm II (everolimus)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Everolimus
Description:
Given PO
Arm group label:
Arm II (everolimus)
Other name:
42-O-(2-Hydroxy)ethyl Rapamycin
Other name:
Afinitor
Other name:
Certican
Other name:
RAD 001
Other name:
RAD-001
Other name:
RAD001
Other name:
Votubia
Other name:
Zortress
Intervention type:
Drug
Intervention name:
Lutetium Lu 177 Dotatate
Description:
Given IV
Arm group label:
Arm I (177Lu-DOTATATE)
Other name:
177 Lu-DOTA-TATE
Other name:
177 Lu-DOTA-Tyr3-Octreotate
Other name:
177Lu-DOTA0-Tyr3-Octreotate
Other name:
Lutathera
Other name:
Lutetium (177Lu) Oxodotreotide
Other name:
Lutetium Lu 177 DOTA(0)-Tyr(3)-Octreotate
Other name:
Lutetium Lu 177-DOTA-Tyr3-Octreotate
Other name:
lutetium Lu 177-DOTATATE
Other name:
Lutetium Oxodotreotide Lu-177
Intervention type:
Other
Intervention name:
Quality-of-Life Assessment
Description:
Ancillary studies
Arm group label:
Arm I (177Lu-DOTATATE)
Arm group label:
Arm II (everolimus)
Other name:
Quality of Life Assessment
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm I (177Lu-DOTATATE)
Arm group label:
Arm II (everolimus)
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
in patients who have previously received 177Lu-DOTATATE for midgut neuroendocrine tumor
(NET) 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 cancer cells. When this radioactive peptide is injected into the body, it
binds to a specific receptor found on some cancer cells. The radioactive peptide builds
up in these cells and helps kill the cancer 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 midgut NET 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 cancer cells from reproducing and by decreasing
blood supply to the cancer cells. Retreating with 177Lu-DOTATATE may work better than
everolimus in shrinking or stabilizing tumor in patients with metastatic and unresectable
NET who were previously treated with 177Lu-DOTATATE.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the effect of lutetium Lu 177 dotatate (177Lu-DOTATATE) versus (vs.)
everolimus on progression-free survival (PFS) in patients with metastatic/unresectable
midgut neuroendocrine tumour (NET) who have progressed following previous peptide
receptor radionuclide therapy (PRRT).
SECONDARY OBJECTIVES:
I. To evaluate the toxicity and safety of 177Lu-DOTATATE and everolimus. II. To determine
the effect of 177Lu-DOTATATE vs. everolimus on overall response rate (ORR).
III. To evaluate the effect of 177Lu-DOTATATE vs. everolimus on overall survival (OS).
IV. To evaluate post progression survival (PPS) and time to second objective disease
progression (PFS2) for patients randomized to Arm 2 of the study and crossed over to Arm
1 at time of objective progression per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1.
V. To evaluate the effect of 177Lu-DOTATATE vs. everolimus on patient quality of life
(QoL).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive 177Lu-DOTATATE intravenously (IV) every 8 weeks (Q8W). Treatment
repeats for two cycles in the absence of disease progression or unacceptable toxicities.
Patients also undergo computed tomography (CT) scan and collection of blood samples while
on study.
ARM II: Patients receive everolimus orally (PO) on a daily basis (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
collection of blood samples while on study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must be at least >= 18 years of age
- Metastatic, histologically confirmed grade 1 or 2 well-differentiated midgut
neuroendocrine tumours, including NETs of unknown primary thought to be of midgut
origin, with positive Gallium-68 DOTATATE scan or Copper-64 DOTATATE 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 will be considered positive if the maximum
standardized uptake value (SUVmax) of target lesion is > SUV mean of normal liver
parenchyma
- 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 a 52-week period. Previous
therapy with everolimus for a maximum period of 1 month is permitted. No previous
targeted alpha therapy is permitted. No previous alkylator therapy (i.e. Temodar) 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
- Have not received any intervening therapy after initial PRRT
- 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 =< criteria 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
everolimus (Arm 2) will not be allowed to continue somatostatin analogues unless
they have functional carcinoid 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
- Patients of childbearing 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. 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
- 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. 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
177Lu-DOTATATE and for 2.5 months following the last treatment
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCHealth University of Colorado Hospital
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
720-848-0650
Investigator:
Last name:
Emily Baiyee-Toegel
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Aventura
Address:
City:
Aventura
Zip:
33180
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
954-461-2180
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Coral Gables
Address:
City:
Coral Gables
Zip:
33146
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Address:
City:
Deerfield Beach
Zip:
33442
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
855-776-0015
Investigator:
Last name:
Patrick W. McGarrah
Email:
Principal Investigator
Facility:
Name:
University of Miami Miller School of Medicine-Sylvester Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Kendall
Address:
City:
Miami
Zip:
33176
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Plantation
Address:
City:
Plantation
Zip:
33324
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
312-695-1301
Email:
cancer@northwestern.edu
Investigator:
Last name:
Al B. Benson
Email:
Principal Investigator
Facility:
Name:
Henry Ford Hospital
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
313-916-3721
Email:
CTOResearch@hfhs.org
Investigator:
Last name:
Gazala Khan
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
855-776-0015
Investigator:
Last name:
Patrick W. McGarrah
Email:
Principal Investigator
Facility:
Name:
University of New Mexico Cancer Center
Address:
City:
Albuquerque
Zip:
87106
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
505-925-0348
Email:
HSC-ClinicalTrialInfo@salud.unm.edu
Investigator:
Last name:
Bernard Tawfik
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-293-5066
Email:
Jamesline@osumc.edu
Investigator:
Last name:
Bhavana Konda
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute/University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-424-2100
Email:
cancerinfo@hci.utah.edu
Investigator:
Last name:
Heloisa P. Soares
Email:
Principal Investigator
Facility:
Name:
BCCA-Vancouver Cancer Centre
Address:
City:
Vancouver
Zip:
V5Z 4E6
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-939-3333
Investigator:
Last name:
Jonathan M. Loree
Email:
Principal Investigator
Facility:
Name:
CancerCare Manitoba
Address:
City:
Winnipeg
Zip:
R3E 0V9
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
866-561-1026
Email:
ctu_web@cancercare.mb.ca
Investigator:
Last name:
Hanbo Zhang
Email:
Principal Investigator
Facility:
Name:
Ottawa Hospital and Cancer Center-General Campus
Address:
City:
Ottawa
Zip:
K1H 8L6
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
613-761-4395
Investigator:
Last name:
Timothy R. Asmis
Email:
Principal Investigator
Facility:
Name:
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Address:
City:
Toronto
Zip:
M4N 3M5
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
416-480-5000
Investigator:
Last name:
Sten D. Myrehaug
Email:
Principal Investigator
Start date:
January 12, 2024
Completion date:
April 30, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05773274
