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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

Primary Purpose

Prostate Adenocarcinoma With Neuroendocrine Differentiation, Prostate Neuroendocrine Carcinoma, Prostate Small Cell Neuroendocrine Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Biospecimen Collection
Computed Tomography
Lutetium Lu 177 Dotatate
Positron Emission Tomography
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Adenocarcinoma With Neuroendocrine Differentiation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Northwestern UniversityRecruiting
  • University of Kentucky/Markey Cancer CenterRecruiting
  • JHU Sidney Kimmel Comprehensive Cancer Center LAORecruiting
  • University of Wisconsin Carbone Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (lutetium Lu 177 dotatate)

Arm Description

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.

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
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

Radiographic progression-free survival (rPFS)
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).
Treatment response
Will be assessed by 18F-FDG PET.
Change in FDG-PET signal
Will be assessed with Quantitative Total Extensible Imaging (QTxI).

Full Information

First Posted
January 18, 2023
Last Updated
September 28, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05691465
Brief Title
Testing the Safety and Effectiveness of Radiation-based Treatment (Lutetium Lu 177 Dotatate) for Metastatic Prostate Cancer That Has Neuroendocrine Cells
Official Title
A Phase II Study of Lutetium Lu 177 Dotatate in Metastatic Prostate Cancer With Neuroendocrine Differentiation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 21, 2023 (Anticipated)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
November 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVE: I. Evaluate the objective response rate for patients treated with lutetium Lu 177 dotatate using Prostate Cancer Working Group (PCWG) 3 criteria. SECONDAY OBJECTIVES: 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. EXPLORATORY OBJECTIVES: 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. OUTLINE: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Adenocarcinoma With Neuroendocrine Differentiation, Prostate Neuroendocrine Carcinoma, Prostate Small Cell Neuroendocrine Carcinoma, Stage IV Prostate Cancer AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (lutetium Lu 177 dotatate)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT scan
Intervention Type
Drug
Intervention Name(s)
Lutetium Lu 177 Dotatate
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
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
Intervention Description
Undergo PET
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
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.
Time Frame
At 6 months
Secondary Outcome Measure Information:
Title
Radiographic progression-free survival (rPFS)
Description
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).
Time Frame
At 6 months
Title
Treatment response
Description
Will be assessed by 18F-FDG PET.
Time Frame
At 6 months
Title
Change in FDG-PET signal
Description
Will be assessed with Quantitative Total Extensible Imaging (QTxI).
Time Frame
Pre-treatment to after 2 doses of lutetium Lu 177 dotatate, assessed up to 16 weeks
Other Pre-specified Outcome Measures:
Title
Gene expression levels of circulating tumor cells
Description
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.
Time Frame
Up to 2 years
Title
Patient-specific dosimetry of lutetium Lu 177 dotatate
Description
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.
Time Frame
Up to 192 hours after first dose of lutetium Lu 177 dotatate

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John M Floberg
Organizational Affiliation
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
312-695-1301
Email
cancer@northwestern.edu
First Name & Middle Initial & Last Name & Degree
Maha H. Hussain
Facility Name
University of Kentucky/Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
859-257-3379
First Name & Middle Initial & Last Name & Degree
Zin W. Myint
Facility Name
JHU Sidney Kimmel Comprehensive Cancer Center LAO
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John M. Floberg
Phone
608-262-6968
Email
jfloberg@humonc.wisc.edu
First Name & Middle Initial & Last Name & Degree
John M. Floberg
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
800-622-8922
First Name & Middle Initial & Last Name & Degree
John M. Floberg

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm

Learn more about this trial

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

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