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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Undergo blood and tissue sample collection
Undergo CT
Given PO
Given FDG
Given IV
Undergo MRI
Undergo PET
Undergo SPECT
Ancillary studies
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
ACTIVE_NOT_RECRUITINGTower Cancer Research Foundation
Beverly Hills, California, United States
RECRUITINGLoma Linda University Medical Center
Loma Linda, California, United States
RECRUITINGCedars Sinai Medical Center
Los Angeles, California, United States
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
Overall survival (OS)
The distribution of OS will be estimated using the method of Kaplan-Meier. The median OS, along with 90% CIs, will be estimated by the two treatment groups. OS will be compared between the two between treatment arms using the stratified log-rank test at a one-sided 10% level of significance.
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)
Defined as the proportion of patients in each arm whose best response is either complete response (CR) or partial response (PR). Will be estimated using point estimates and 95% CIs according to the methods in Duffy and Santner.
Time frame: Up to 5 years from study registration
Incidence of adverse events
Will evaluate and compare the toxicity profile of lutetium Lu 177 dotatate and everolimus. As per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, the term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to the study treatment.
Time frame: Up to 5 years from study registration
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
UCSF Medical Center-Mission Bay
San Francisco, California, United States
RECRUITINGTorrance Memorial Physician Network - Cancer Care
Torrance, California, United States
RECRUITINGMedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
SUSPENDEDUM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
RECRUITING...and 19 more locations