Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors
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|ClinicalTrials.gov Identifier: NCT04665739|
Recruitment Status : Not yet recruiting
First Posted : December 14, 2020
Last Update Posted : September 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Lung Carcinoid Tumor Functioning Lung Carcinoid Tumor Locally Advanced Lung Neuroendocrine Neoplasm Lung Atypical Carcinoid Tumor Lung Neuroendocrine Neoplasm Lung Typical Carcinoid Tumor Metastatic Lung Carcinoid Tumor Metastatic Lung Neuroendocrine Neoplasm Non-Functioning Lung Carcinoid Tumor Recurrent Lung Neuroendocrine Neoplasm Unresectable Lung Carcinoid Tumor Unresectable Lung Neuroendocrine Neoplasm||Drug: Everolimus Drug: Lutetium Lu 177 Dotatate||Phase 2|
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).
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.
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. Treatment repeats every 56 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive everolimus orally (PO) once daily (QD) on days 1-28. 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.
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 (Clinical Trial)|
|Estimated Enrollment :||108 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Phase II Trial of Lutetium Lu 177 Dotatate Versus Everolimus in Somatostatin Receptor Positive Bronchial Neuroendocrine Tumors|
|Estimated Study Start Date :||September 10, 2021|
|Estimated Primary Completion Date :||July 1, 2024|
|Estimated Study Completion Date :||July 1, 2024|
Experimental: Arm I (lutetium Lu 177 dotatate)
Patients receive lutetium Lu 177 dotatate IV over 30-40 minutes on day 1. Treatment repeats every 56 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Lutetium Lu 177 Dotatate
Active Comparator: Arm II (everolimus)
Patients receive everolimus PO QD on days 1-28. 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.
- Median progression-free survival (PFS) [ Time Frame: From randomization until either radiographic progression confirmed by central radiology review or death, assessed up to 5 years from study registration ]Will be compared between patients with a bronchial neuroendocrine tumor (NET) 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.
- 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 ]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.
- Overall response rate (ORR) [ Time Frame: Up to 5 years from study registration ]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.
- Incidence of adverse events [ Time Frame: Up to 5 years from study registration ]Will evaluate and compare the toxicity profile of lutetium Lu 177 dotatate and everolimus. As per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, the term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to the study treatment.
- Incidence of late toxicities of lutetium Lu 177 dotatate therapy [ Time Frame: More than 30 days after treatment ]The incidence of grade 3+ late toxicities will be analyzed in a descriptive manner. Incidence will be described for each treatment arm. Frequency tables will be reviewed for patterns.
- Pretreatment disease burden [ Time Frame: Baseline ]
- Somatostatin receptor status on DOTATATE PET (or other SSTR-PET) [ Time Frame: Up to 5 years from study registration ]
- Dosimetry of response [ Time Frame: Up to 5 years from study registration ]
- Response rate [ Time Frame: Up to 5 years from study registration ]The proportion of patients in each carcinoid group with either CR or PR as their best response will be estimated using point estimates and 95% CIs according to the methods in Duffy and Santner. ORR will be compared between treatment arms using the 2-sample z-test to compare sample proportion at a one-sided 5% level of significance.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04665739
|Principal Investigator:||Thomas A Hope||Alliance for Clinical Trials in Oncology|