RECRUITING

Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors

Conditions

Advanced Lung Neuroendocrine Tumor Functioning Lung Neuroendocrine Tumor Locally Advanced Lung Neuroendocrine Neoplasm Lung Neuroendocrine Neoplasm Lung Neuroendocrine Tumor G1 Lung Neuroendocrine Tumor G2 Metastatic Lung Neuroendocrine Neoplasm Metastatic Lung Neuroendocrine Tumor Non-Functioning Lung Neuroendocrine Tumor Recurrent Lung Neuroendocrine Neoplasm Unresectable Lung Neuroendocrine Neoplasm Unresectable Lung Neuroendocrine Tumor

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-02-03

Study Completion:2025-07-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04665739

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 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 or other ablative treatment must be completed at least 28 days prior to registration * REGISTRATION: Prior treatment with 90-Yttrium radioembolization must be completed at least 3 months 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, because this study involves: * An investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown, and * An agent that has known genotoxic, mutagenic, and teratogenic effects * Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 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 * Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 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	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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 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 or other ablative treatment must be completed at least 28 days prior to registration
* REGISTRATION: Prior treatment with 90-Yttrium radioembolization must be completed at least 3 months 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, because this study involves:
* An investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown, and
* An agent that has known genotoxic, mutagenic, and teratogenic effects
* Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 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
* Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 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

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Thomas A Hope

PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Study Locations (Sites)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233

United States

Tower Cancer Research Foundation

Beverly Hills, California, 90211

United States

Cedars Sinai Medical Center

Los Angeles, California, 90048

United States

UCSF Medical Center-Mission Bay

San Francisco, California, 94158

United States

Torrance Memorial Physician Network - Cancer Care

Torrance, California, 90505

United States

MedStar Georgetown University Hospital

Washington, District of Columbia, 20007

United States

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180

United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146

United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442

United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136

United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324

United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637

United States

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451

United States

University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462

United States

Mission Cancer and Blood - Ankeny

Ankeny, Iowa, 50023

United States

Iowa Methodist Medical Center

Des Moines, Iowa, 50309

United States

Mission Cancer and Blood - Des Moines

Des Moines, Iowa, 50309

United States

Alliance for Clinical Trials in Oncology

Boston, Massachusetts, 02115

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

United States

Case Western Reserve University

Cleveland, Ohio, 44106

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

United States

Temple University Hospital

Philadelphia, Pennsylvania, 19140

United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Thomas A Hope, PRINCIPAL_INVESTIGATOR, Alliance for Clinical Trials in Oncology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-02-03

Study Completion Date2025-07-01

Study Record Updates

Study Start Date2023-02-03

Study Completion Date2025-07-01

Terms related to this study

Additional Relevant MeSH Terms

Advanced Lung Neuroendocrine Tumor
Functioning Lung Neuroendocrine Tumor
Locally Advanced Lung Neuroendocrine Neoplasm
Lung Neuroendocrine Neoplasm
Lung Neuroendocrine Tumor G1
Lung Neuroendocrine Tumor G2
Metastatic Lung Neuroendocrine Neoplasm
Metastatic Lung Neuroendocrine Tumor
Non-Functioning Lung Neuroendocrine Tumor
Recurrent Lung Neuroendocrine Neoplasm
Unresectable Lung Neuroendocrine Neoplasm
Unresectable Lung Neuroendocrine Tumor