Clinical trial Recruiting at 23 sites Phase 2 Interventional Ages 18 and up

Testing a radioactive drug for advanced bronchial neuroendocrine tumors

Official title: Randomized Phase II Trial of Lutetium Lu 177 Dotatate Versus Everolimus in Somatostatin Receptor Positive Bronchial Neuroendocrine Tumors

Run by National Cancer Institute (NCI) · NCT04665739 · Data updated 2026-11-12

This study is testing a new radioactive drug called lutetium Lu 177 dotatate to see if it can help people with advanced bronchial neuroendocrine tumors live longer and feel better compared to the standard treatment.

Quick facts

PhasePhase 2
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment70 (estimated)
SponsorNational Cancer Institute (NCI)
NIH
Drugs / interventionsRadiation
Locations29 sites (Birmingham, Alabama and 28 other locations)
StatusRecruiting
StartedFebruary 3, 2023
Main results expectedSeptember 1, 2032
Study endsSeptember 1, 2032
Registry record updatedNovember 5, 2026
Trial IDNCT04665739 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Ideal candidates include patients with well- or moderately-differentiated bronchial neuroendocrine tumors that are somatostatin receptor positive.

Probably not a fit

Patients with poorly-differentiated or high-grade neuroendocrine carcinomas are unlikely to benefit from this study.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase II trial evaluates the effectiveness of lutetium Lu 177 dotatate compared to the standard treatment, everolimus, in patients with somatostatin receptor positive advanced bronchial neuroendocrine tumors. The study aims to determine if lutetium Lu 177 dotatate can improve progression-free survival and overall survival rates. Patients will receive the treatment intravenously over several cycles, and their responses will be monitored through imaging and toxicity assessments. The trial also explores the long-term effects of the treatment and its efficacy based on tumor characteristics.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with advanced bronchial neuroendocrine tumors.

How similar studies have gone: Other studies have shown promise with similar radioconjugate approaches, suggesting potential for success in this trial.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* PRE-REGISTRATION: Pathologic Documentation: Well- or moderately-differentiated neuroendocrine tumor(s) of bronchial origin (i.e. carcinoid) as assessed by local pathology

  * The pathology report must state ONE of the following:

    * Well- or moderately-differentiated neuroendocrine tumor,
    * Low- or intermediate-grade neuroendocrine tumor, or
    * Carcinoid tumor (including typical or atypical carcinoid tumors)
* PRE-REGISTRATION: Documentation of histology from a primary or metastatic site is allowed
* PRE-REGISTRATION: Functional (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome) or nonfunctional tumors are allowed
* PRE-REGISTRATION: Patients with poorly-differentiated or high-grade neuroendocrine carcinoma (i.e. large cell neuroendocrine carcinoma of lung, small cell lung cancer) or mixed tumors (i.e. adenocarcinoid tumor) are not eligible
* PRE-REGISTRATION: Recurrent or locally-advanced/unresectable or metastatic disease
* PRE-REGISTRATION: Neuroendocrine tumor of bronchial (i.e. lung) primary site
* PRE-REGISTRATION: Lesions must have shown radiological evidence of disease progression in the 12 months prior to pre-registration

  * Tumor must have shown somatostatin receptor (SSTR) positivity on 68Ga-DOTATATE PET or other SSTR-PET scan in the 12 months prior to pre-registration; however, documentation of SSTR positivity in the 6 months prior to pre-registration is preferred. SSTR positivity is defined as uptake greater than background liver in all measurable lesions
* PRE-REGISTRATION: Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by computer tomography (CT) scan or magnetic imaging (MRI). Any lesions which have undergone percutaneous therapies or radiotherapy should not be considered measurable unless the lesion has clearly progressed since the procedure
* PRE-REGISTRATION: Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 1 cm with CT or MRI (or \>= 1.5 cm short axis for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, bone metastases, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung
* REGISTRATION: Confirmation of SSTR positivity by Alliance Imaging Core Lab (ICL) at Imaging and Radiation Oncology Core (IROC) Ohio central radiographic review
* REGISTRATION: Patients with treatment-naive or previously-treated disease are allowed. Patients with previously-treated disease must have demonstrated radiographic disease progression on the prior therapy
* REGISTRATION: No prior treatment with peptide receptor radionuclide therapy (PRRT) (e.g. lutetium Lu 177 dotatate)
* REGISTRATION: No prior treatment with mammalian target of rapamycin (mTOR) inhibitors (e.g. deforolimus, everolimus, sirolimus, temsirolimus, etc.)
* REGISTRATION: Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective radioembolization) or ablative therapies (i.e. cryoablation, radiofrequency ablation, etc.) is allowed if measurable disease remains outside of the treated area or if there is documented disease progression in a treated site. Prior liver-directed (including ablative) treatment must be completed at least 28 days prior to registration
* REGISTRATION: Prior treatment with 90-Yttrium radioembolization must be completed at least 6-weeks prior to registration
* REGISTRATION: Radiation therapy to the lung and/or mediastinum must be completed at least 14 days prior to registration for stereotactic ablative and at least 28 days prior to registration for conventional fractionation
* REGISTRATION: Prior treatment with systemic anticancer therapy must be completed at least 28 days prior to registration (except for somatostatin analogs in patients with functional tumors). Continuation of treatment with somatostatin analogs while on protocol therapy is allowed provided that the patient:

  * Has functional tumors (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome), and
  * Has previously demonstrated radiographic disease progression while on somatostatin analog therapy
* REGISTRATION: Patients must have completed any major surgery at least 28 days prior to registration. Complete wound healing from major surgery should occur prior to registration
* REGISTRATION: Patients should have improvement of any toxic effects of prior therapy (except alopecia, fatigue, and other non-reversible toxic effects such as neuropathy from cisplatin) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, grade 1 or less
* REGISTRATION: Not pregnant and not nursing

  * Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 28 days prior to registration is required
* REGISTRATION: Age \>= 18 years
* REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* REGISTRATION: Hemoglobin \>= 8.0 g/dL
* REGISTRATION: Platelet count \>= 75,000/mm\^3
* REGISTRATION: Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* REGISTRATION: Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance \>= 40 mL/min

  * Calculated by the Cockcroft-Gault equation
* REGISTRATION: Total bilirubin =\< 2.0 x ULN

  * In patients with Gilbert's syndrome, if total bilirubin is \> 2.0 x ULN, then direct bilirubin must be =\< 2.0 x ULN
* REGISTRATION: Albumin \>= 2.8 g/dL
* REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x ULN
* REGISTRATION: No known central nervous system metastases unless treated and clinically stable for at least 14 days prior to registration. Patients on steroid support must be clinically stable on weaning doses of steroids
* REGISTRATION: No other currently active malignancy that requires therapy or is expected to require therapy during the study (excluding non-melanoma skin cancers or in situ carcinomas, such as breast or cervical)
* REGISTRATION: No known active hepatitis B (defined as hepatitis B surface antigen \[HbsAg\] reactive) or known active hepatitis C virus (defined as hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] viral load detected). The exception is for patients with known active hepatitis B virus (defined as HbsAg reactive) infection, where the HBV viral load must be undetectable on suppressive therapy for patient to be eligible
* REGISTRATION: Patients with known human immunodeficiency virus (HIV) infections on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
* REGISTRATION: No known active or uncontrolled infections requiring ongoing antifungals or antibiotics in the 3 days prior to registration
* REGISTRATION: No receipt of live attenuated vaccines in the 7 days prior to registration
* REGISTRATION: No known decompensated liver cirrhosis
* REGISTRATION: No known prior drug-induced pneumonitis that was symptomatic or required treatment
* REGISTRATION: No known medical condition causing an inability to swallow and no known impairment of gastrointestinal function that may significantly alter the absorption of an oral agent
* REGISTRATION: No known hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus, etc.)
* REGISTRATION: Concurrent somatostatin analog use while on protocol therapy is allowed provided that the patient: 1) has a functional tumor (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome), 2) has previously demonstrated radiographic disease progression while on somatostatin analog therapy
* REGISTRATION: Chronic concomitant treatment with P-gp and strong CYP3A4 inhibitors and/or inducers is not allowed on the everolimus treatment arm of this study. Given that the study is randomized, all patients on P-gp and strong CYP3A4 inhibitors and/or inducers must discontinue the drug(s) 7 days prior to registration
* RE-REGISTRATION: Confirmation of disease progression by RECIST v1.1 by real-time Alliance ICL at IROC Ohio central radiographic review
* RE-REGISTRATION: Not pregnant and not nursing

  * Women of childbearing potential only, a negative pregnancy test done =\< 28 days prior to re-registration is required
* RE-REGISTRATION: ECOG performance status 0-2
* RE-REGISTRATION: Hemoglobin \>= 8.0 g/dL
* RE-REGISTRATION: Platelet count \>= 75,000/mm\^3
* RE-REGISTRATION: Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* RE-REGISTRATION: Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance \>= 40 mL/min

  * Calculated by the Cockcroft-Gault equation
* RE-REGISTRATION: Total bilirubin =\< 2.0 x ULN

  * In patients with Gilbert's syndrome, if total bilirubin is \> 2.0 x ULN, then direct bilirubin must be =\< 2.0 x ULN
* RE-REGISTRATION: Albumin \>= 2.8 g/dL
* RE-REGISTRATION: AST/ALT =\< 3.0 x ULN

Where it's running

  • Tower Cancer Research Foundation
    Beverly Hills, California, United States
    Recruiting
  • Cedars-Sinai Medical Center
    Los Angeles, California, United States
    Recruiting
  • UCSF Medical Center-Mission Bay
    San Francisco, California, United States
    Recruiting
  • Torrance Memorial Physician Network - Cancer Care
    Torrance, California, United States
    Recruiting
  • UM Sylvester Comprehensive Cancer Center at Coral Gables
    Coral Gables, Florida, United States
    Recruiting
  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    Deerfield Beach, Florida, United States
    Recruiting
Show 23 more locations
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida, United States
    Recruiting
  • UM Sylvester Comprehensive Cancer Center at Plantation
    Plantation, Florida, United States
    Recruiting
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois, United States
    Recruiting
  • UC Comprehensive Cancer Center at Silver Cross
    New Lenox, Illinois, United States
    Recruiting
  • University of Chicago Medicine-Orland Park
    Orland Park, Illinois, United States
    Recruiting
  • UI Health Care Mission Cancer and Blood - Ankeny Clinic
    Ankeny, Iowa, United States
    Recruiting
  • Iowa Methodist Medical Center
    Des Moines, Iowa, United States
    Recruiting
  • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    Des Moines, Iowa, United States
    Recruiting
  • Dana-Farber Cancer Institute
    Boston, Massachusetts, United States
    Recruiting
  • Mayo Clinic in Rochester
    Rochester, Minnesota, United States
    Recruiting
  • Missouri Baptist Medical Center
    St Louis, Missouri, United States
    Recruiting
  • Case Western Reserve University
    Cleveland, Ohio, United States
    Recruiting
  • Ohio State University Comprehensive Cancer Center
    Columbus, Ohio, United States
    Recruiting
  • Fox Chase Cancer Center
    Philadelphia, Pennsylvania, United States
    Recruiting
  • Temple University Hospital
    Philadelphia, Pennsylvania, United States
    Recruiting
  • UPMC Hillman Cancer Center
    Pittsburgh, Pennsylvania, United States
    Recruiting
  • Huntsman Cancer Institute/University of Utah
    Salt Lake City, Utah, United States
    Recruiting
  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama, United States
    Withdrawn
  • Loma Linda University Medical Center
    Loma Linda, California, United States
    Suspended
  • MedStar Georgetown University Hospital
    Washington D.C., District of Columbia, United States
    Suspended
  • UM Sylvester Comprehensive Cancer Center at Aventura
    Aventura, Florida, United States
    Suspended
  • Duke University Medical Center
    Durham, North Carolina, United States
    Suspended
  • Vanderbilt University/Ingram Cancer Center
    Nashville, Tennessee, United States
    Suspended

Study contacts

  • Principal investigator: Thomas A Hope — Alliance for Clinical Trials in Oncology

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.