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Testing the Safety and Effectiveness of Radiation-based Treatment (Lutetium Lu 177 Dotatate) for Metastatic Prostate Cancer That Has Neuroendocrine Cells

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05691465
Recruitment Status : Recruiting
First Posted : January 20, 2023
Last Update Posted : September 29, 2023
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial studies how well lutetium Lu 177 dotatate works in treating patients with prostate cancer with neuroendocrine differentiation that has spread to other places in the body (metastatic). Neuroendocrine differentiation refers to cells that have traits of both hormone-producing endocrine cells and nerve cells. These cells release hormones into the blood in response to a signal from the nervous system. Hormones are biological substances that circulate through the bloodstream to control the activity of other organs or cells in the body. 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. Treatment with Lutetium Lu 177 dotatate may shrink the tumor in a way that can be measured in patients with metastatic prostate cancer with neuroendocrine differentiation.

Condition or disease Intervention/treatment Phase
Prostate Adenocarcinoma With Neuroendocrine Differentiation Prostate Neuroendocrine Carcinoma Prostate Small Cell Neuroendocrine Carcinoma Stage IV Prostate Cancer AJCC v8 Procedure: Biospecimen Collection Procedure: Computed Tomography Drug: Lutetium Lu 177 Dotatate Procedure: Positron Emission Tomography Phase 2

Detailed Description:


I. Evaluate the objective response rate for patients treated with lutetium Lu 177 dotatate using Prostate Cancer Working Group (PCWG) 3 criteria.


I. Evaluate the 6-month radiographic progression-free survival of neuroendocrine-differentiated prostate cancer treated with lutetium Lu 177 dotatate.

II. Determine if the change in fludeoxyglucose (FDG)-positron emission tomography (PET) signal from pre-treatment to after 2 doses of lutetium Lu 177 dotatate correlates with objective response rate.


I. Evaluate the potential to perform patient-specific dosimetry of lutetium Lu 177 dotatate using gamma imaging to predict treatment response and renal toxicity.

II. Perform gene expression analysis of circulating tumor cells to identify pre-treatment biomarkers of response and signatures of resistance at the time of progression.


Patients receive lutetium Lu 177 dotatate intravenously (IV) over 30 minutes. Cycles repeat every 6 weeks (Q6W) for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (CT) scan at baseline and collection of blood throughout the trial.

Patients are followed up at 6 weeks after last dose lutetium Lu 177 dotatate and then every 3 months for 2 years after removal from study or until death, whichever occurs first.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Lutetium Lu 177 Dotatate in Metastatic Prostate Cancer With Neuroendocrine Differentiation
Estimated Study Start Date : October 21, 2023
Estimated Primary Completion Date : November 1, 2024
Estimated Study Completion Date : November 1, 2024

Arm Intervention/treatment
Experimental: Treatment (lutetium Lu 177 dotatate)
Patients receive lutetium Lu 177 dotatate IV over 30 minutes. Cycles repeat Q6W for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT scan at baseline and collection of blood throughout the trial.
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography

Drug: Lutetium Lu 177 Dotatate
Given IV
Other Names:
  • 177 Lu-DOTA-TATE
  • 177 Lu-DOTA-Tyr3-Octreotate
  • 177Lu-DOTA0-Tyr3-Octreotate
  • Lutathera
  • Lutetium Lu 177 DOTA(0)-Tyr(3)-Octreotate
  • Lutetium Lu 177-DOTA-Tyr3-Octreotate
  • lutetium Lu 177-DOTATATE
  • Lutetium Oxodotreotide Lu-177

Procedure: Positron Emission Tomography
Undergo PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron emission tomography (procedure)
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT

Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: At 6 months ]
    The objective response rate according to Prostate Cancer Working Group (PCWG) 3 criteria will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR will be reported along with the corresponding two-sided 95% confidence interval. The confidence interval will be adjusted for the two-stage design structure. This analysis will be based on the intent-to-treat population.

Secondary Outcome Measures :
  1. Radiographic progression-free survival (rPFS) [ Time Frame: At 6 months ]
    Will be determined by PCWG3 criteria. Specifically, progression/response will be determined via RECIST 1.1 criteria using diagnostic computed tomography (CT) scans of the chest/abdomen/pelvis to analyze progressive disease (PD), stable disease (SD), complete response (CR), partial response (PR), and toxicity type/grade. Progression and response will also be assessed by fludeoxyglucose positron emission tomography (18F-FDG PET).

  2. Treatment response [ Time Frame: At 6 months ]
    Will be assessed by 18F-FDG PET.

  3. Change in FDG-PET signal [ Time Frame: Pre-treatment to after 2 doses of lutetium Lu 177 dotatate, assessed up to 16 weeks ]
    Will be assessed with Quantitative Total Extensible Imaging (QTxI).

Other Outcome Measures:
  1. Gene expression levels of circulating tumor cells [ Time Frame: Up to 2 years ]
    Will be summarized using descriptive statistics. Expression levels of candidate markers will be correlated with radiographic time to progression using univariate Cox proportional hazard regression analysis. The Benjamini-Hochberg false discovery rate method will be utilized to control the false discovery rate when evaluating the markers. Machine learning methods will be used to identify signatures of resistance at the time of progression.

  2. Patient-specific dosimetry of lutetium Lu 177 dotatate [ Time Frame: Up to 192 hours after first dose of lutetium Lu 177 dotatate ]
    Descriptive analyses will be conducted to evaluate the potential to perform patient-specific dosimetry of lutetium Lu 177 dotatate using gamma imaging to predict treatment response and renal toxicity. Imaging outcome parameters will be summarized in terms of means, medians, standard deviations and ranges, stratified by assessment time point (24, 96, and 192 hours post-injection), stratified by response (PD, SD versus CR, PR) and toxicity type/grade.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have metastatic prostate cancer with neuroendocrine differentiation, as determined by at least one of the following:

    • Histologically confirmed small cell or neuroendocrine cancer from a primary prostate or metastatic biopsy. Neuroendocrine prostate cancer includes mixed small cell with adenocarcinoma histology, as well as small or large cells with positive neuroendocrine markers (e.g., chromogranin or synaptophysin)
    • Prostate adenocarcinoma with molecular features of neuroendocrine differentiated cancer (e.g., 2 of the following 3: PTEN, TP53, or RB loss)
    • Progression of visceral metastases in the absence of PSA progression
    • Serum chromogranin A > 5x normal limit, or neuron-specific enolase > 2x normal
  • Age >= 18 years. Prostate cancer is typically a disease of older men, with the average age at diagnosis being 65 years. Consequently, because the research topic is not relevant to children, no children will be included in this study. There is no upper limit to the age of participants eligible for this study
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8 g/dL, prior to each dose of lutetium lu 177 dotatate
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
  • Creatinine Cockcroft calculated creatinine clearance of >= 60 mL/min OR
  • Glomerular filtration rate (GFR) of 60 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients should be New York Heart Association Functional Classification of class 2B or better
  • Current disease progression according to PCWG3 criteria
  • Ongoing use of luteinizing hormone-releasing hormone (LHRH) agonists/antagonists will be required (unless prior bilateral orchiectomy or pure neuroendocrine carcinoma histology) to maintain testosterone at castrate levels. Patients with a pure neuroendocrine carcinoma histology do not need to be undergoing LHRH agonist/antagonist therapy
  • No concurrent use of other anti-cancer therapies
  • Pregnancy Precaution: The effects of lutetium lu 177 dotatate on the developing human fetus are unknown. For this reason and because radionuclides are known to be teratogenic, male participants and their female partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of lutetium lu 177 dotatate administration. Patients must not donate sperm during the study and for 3 months after the last study drug administration
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible
  • Patients will undergo a Gallium 68 Dotatate PET scan after enrollment. The Gallium 68 Dotatate PET must be positive to proceed with lutetium Lu 177 dotatate therapy. A positive scan will be defined as at least one lesion with an maximum standardized uptake value (SUVmax) > the average standardized uptake value (SUV) of normal liver. The positive lesion(s) can be in any location (bone metastases or visceral metastases). Patients with only bone metastases will be allowed

Exclusion Criteria:

  • Patients who are receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Lutetium Lu 177 dotatate
  • As per the Food and Drug Administration (FDA) package insert for Lutetium Lu 177 dotatate, use of long-acting somatostatin analogs (e.g., long-acting octreotide) is prohibited within 4 weeks prior to initiating Lutetium Lu 177 dotatate and during treatment. Use of short-acting somatostatin analogs is prohibited within 24 hours prior to initiating Lutetium Lu 177 dotatate and during treatment. Long-acting somatostatin analogs or short-acting somatostatin analogs will be allowed if the patient has a history of carcinoid syndrome and requires long-acting or short-acting somatostatin analogs for the control of his functional syndrome
  • Patients with uncontrolled intercurrent illness
  • Any of the following within 6 months before starting treatment: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV
  • Uncontrolled hypertension as indicated by a systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg at screening

Information from the National Library of Medicine

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 identifier (NCT number): NCT05691465

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United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Site Public Contact    312-695-1301   
Principal Investigator: Maha H. Hussain         
United States, Kentucky
University of Kentucky/Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Contact: Site Public Contact    859-257-3379      
Principal Investigator: Zin W. Myint         
United States, Maryland
JHU Sidney Kimmel Comprehensive Cancer Center LAO Recruiting
Baltimore, Maryland, United States, 21231
Contact: John M. Floberg    608-262-6968   
Principal Investigator: John M. Floberg         
United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Site Public Contact    800-622-8922      
Principal Investigator: John M. Floberg         
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: John M Floberg JHU Sidney Kimmel Comprehensive Cancer Center LAO
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT05691465    
Other Study ID Numbers: NCI-2022-05173
NCI-2022-05173 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10487 ( Other Identifier: JHU Sidney Kimmel Comprehensive Cancer Center LAO )
10487 ( Other Identifier: CTEP )
UM1CA186691 ( U.S. NIH Grant/Contract )
First Posted: January 20, 2023    Key Record Dates
Last Update Posted: September 29, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Prostatic Neoplasms
Carcinoma, Small Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Lutetium Lu 177 dotatate
Molecular Mechanisms of Pharmacological Action