Randomized Phase II Trial of Lutetium Lu 177 Dotatate Versus Everolimus in Somatostatin Receptor Positive Bronchial Neuroendocrine Tumors
Summary
This phase II trial studies the effect of lutetium Lu 177 dotatate compared to the usual treatment (everolimus) in treating patients with somatostatin receptor positive bronchial neuroendocrine tumors that have spread to other places in the body (advanced). Lutetium Lu 177-dotate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177-dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Lutetium Lu 177 dotatate may be more effective than everolimus in shrinking or stabilizing advanced bronchial neuroendocrine tumors.
Detailed description
PRIMARY OBJECTIVE: I. To compare progression-free survival (PFS) of receiving lutetium Lu 177 dotatate to that of receiving everolimus in patients with bronchial neuroendocrine tumor (NET). SECONDARY OBJECTIVES: I. To compare the overall survival (OS) of receiving lutetium Lu 177 dotatate versus everolimus in patients with bronchial NET. II. To compare the overall response rate (ORR) associated with lutetium Lu 177 dotatate versus everolimus in patients with bronchial NET. III. To evaluate and compare the toxicity profile of lutetium Lu 177 dotatate and everolimus. EXPLORATORY OBJECTIVES: I. To study late toxicities of lutetium Lu 177 dotatate therapy including renal dysfunction, myelodysplastic syndrome, and acute leukemia. II. To study the impact of pretreatment disease burden, somatostatin receptor status on lutetium Lu 177 dotatate (DOTATATE) positron emission tomography (PET) (or other somatostatin receptor \[SSTR\]-PET), and measured dosimetry of response. III. To evaluate the response rate (RR) and other efficacy parameters in typical and atypical carcinoid based on central retrospective pathology review. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive lutetium Lu 177 dotatate intravenously (IV) over 30-40 minutes on day 1 of each cycle. Treatment repeats every 56 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET during screening. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on the trial as well as fludeoxyglucose F-18 (FDG) PET and single photon emission computed tomography (SPECT) on the trial. Additionally, patients undergo blood and tissue sample collection during screening and on the trial. ARM II: Patients receive everolimus orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may be able to cross-over to Arm I. Patients undergo PET during screening. Patients also undergo CT or MRI during screening and on the trial as well as FDG PET and SPECT on the trial. Additionally, patients undergo blood and tissue sample collection during screening and on the trial. After completion of study treatment, patients are followed up every 3 months until disease progression and then every 6 months for up to 5 years following study registration.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo blood and tissue sample collection
- ProcedureComputed Tomography
Undergo CT
- DrugEverolimus
Given PO
- OtherFludeoxyglucose F-18
Given FDG
- DrugLutetium Lu 177 Dotatate
Given IV
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- ProcedurePositron Emission Tomography
Undergo PET
- ProcedureSingle Photon Emission Computed Tomography
Undergo SPECT
- OtherSurvey Administration
Ancillary studies
Outcome measures
Primary
Median progression-free survival (PFS)
Will be compared between patients with a bronchial neuroendocrine tumor receiving lutetium Lu 177 dotatate to those receiving everolimus. The distribution of PFS will be estimated using the Kaplan Meier method. Will be tested using a one-sided stratified log rank test. The median PFS, along with 90% confidence intervals (CIs), will be estimated for the two treatment groups.
Time frame: From randomization until either radiographic progression confirmed by central radiology review or death, assessed up to 5 years from study registration
Secondary
Overall survival (OS)
Time frame: From randomization until death due to any cause, with patients censored at the last date known to be alive or last contact date, assessed up to 5 years from study registration
Overall response rate (ORR)
Time frame: Up to 5 years from study registration
Incidence of adverse events
Time frame: Up to 5 years from study registration
Eligibility criteria
Study locations (29)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Tower Cancer Research Foundation
Beverly Hills, California, 90211
Loma Linda University Medical Center
Loma Linda, California, 92354
Cedars-Sinai Medical Center
Los Angeles, California, 90048
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Torrance Memorial Physician Network - Cancer Care
Torrance, California, 90505
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Duke University Medical Center
Durham, North Carolina, 27710
Case Western Reserve University
Cleveland, Ohio, 44106
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Temple University Hospital
Philadelphia, Pennsylvania, 19140
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112