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

Who is this study for? Patients with Lung Cancer
Status: Recruiting
Location: See all (29) locations...
Intervention Type: Procedure, Other, Drug
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

Locations
United States
Alabama
University of Alabama at Birmingham Cancer Center
ACTIVE_NOT_RECRUITING
Birmingham
California
Tower Cancer Research Foundation
RECRUITING
Beverly Hills
Loma Linda University Medical Center
RECRUITING
Loma Linda
Cedars Sinai Medical Center
RECRUITING
Los Angeles
UCSF Medical Center-Mission Bay
RECRUITING
San Francisco
Torrance Memorial Physician Network - Cancer Care
RECRUITING
Torrance
Washington, D.c.
MedStar Georgetown University Hospital
RECRUITING
Washington D.c.
Florida
UM Sylvester Comprehensive Cancer Center at Aventura
RECRUITING
Aventura
UM Sylvester Comprehensive Cancer Center at Coral Gables
RECRUITING
Coral Gables
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
RECRUITING
Deerfield Beach
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING
Miami
UM Sylvester Comprehensive Cancer Center at Plantation
RECRUITING
Plantation
Iowa
UI Health Care Mission Cancer and Blood - Ankeny Clinic
RECRUITING
Ankeny
Iowa Methodist Medical Center
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic
RECRUITING
Des Moines
Illinois
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
UC Comprehensive Cancer Center at Silver Cross
RECRUITING
New Lenox
University of Chicago Medicine-Orland Park
RECRUITING
Orland Park
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
Minnesota
Mayo Clinic in Rochester
RECRUITING
Rochester
Missouri
Missouri Baptist Medical Center
RECRUITING
St Louis
North Carolina
Duke University Medical Center
RECRUITING
Durham
Ohio
Case Western Reserve University
RECRUITING
Cleveland
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
Pennsylvania
Fox Chase Cancer Center
RECRUITING
Philadelphia
Temple University Hospital
RECRUITING
Philadelphia
University of Pittsburgh Cancer Institute (UPCI)
RECRUITING
Pittsburgh
Tennessee
Vanderbilt University/Ingram Cancer Center
SUSPENDED
Nashville
Utah
Huntsman Cancer Institute/University of Utah
RECRUITING
Salt Lake City
Time Frame
Start Date: 2023-02-03
Estimated Completion Date: 2033-01-16
Participants
Target number of participants: 70
Treatments
Experimental: Arm I (lutetium Lu 177 dotatate)
Patients receive lutetium Lu 177 dotatate 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 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.
Active_comparator: Arm II (everolimus)
Patients receive everolimus PO 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.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov