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

Inclusion Criteria:

• PRE-REGISTRATION ELIGIBILITY

• 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 primaryprostate or metastatic biopsy. Neuroendocrine prostate cancer includes mixedsmall cell with adenocarcinoma histology, as well as small or large cells withpositive neuroendocrine markers (e.g., chromogranin or synaptophysin)

• Prostate adenocarcinoma with molecular features of neuroendocrinedifferentiated 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 normalNOTE: Both patients who have had prior cytotoxic chemotherapy and patients whohave never had cytotoxic chemotherapy for prostate cancer will be allowed

• Age >= 18 years. Prostate cancer is typically a disease of older men, with theaverage age at diagnosis being 65 years. Consequently, because the research topic isnot relevant to children, no children will be included in this study. There is noupper 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 xinstitutional ULN

• Creatinine Cockcroft calculated creatinine clearance of >= 40 mL/min

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treatedand cured. For patients with HCV infection who are currently on treatment, they areeligible if they have an undetectable HCV viral load.

• Patients with treated brain metastases are eligible if follow-up brain imaging aftercentral nervous system (CNS)-directed therapy shows no evidence of progression

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

• Patients should be New York Heart Association Functional Classification of class 2Bor better

• Current disease progression according to PCWG3 criteria

• Ongoing use of luteinizing hormone-releasing hormone (LHRH) agonists/antagonistswill be required (unless prior bilateral orchiectomy or pure neuroendocrinecarcinoma histology) to maintain testosterone at castrate levels. Patients with apure neuroendocrine carcinoma histology do not need to be undergoing LHRHagonist/antagonist therapy

• No concurrent use of other anti-cancer therapies

• Pregnancy Precaution: The effects of lutetium lu 177 dotatate on the developinghuman fetus are unknown. For this reason and because radionuclides are known to beteratogenic, male participants and their female partners must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry and for the duration of study participation. Should a woman becomepregnant or suspect she is pregnant while her male partner is participating in thisstudy, she should inform her treating physician immediately. Men treated or enrolledon 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 lutetiumlu 177 dotatate administration. Patients must not donate sperm during the study andfor 3 months after the last study drug administration

• Ability to understand and the willingness to sign a written informed consentdocument. Participants with impaired decision-making capacity who have alegally-authorized representative (LAR) and/or family member available will also beeligible

• 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. Apositive scan will be defined as at least one lesion with an maximum standardizeduptake value (SUVmax) > the average standardized uptake value (SUV) of normal liver.The positive lesion(s) can be in any location (bone metastases or visceralmetastases). Patients with only bone metastases will be allowed

• REGISTRATION ELIGIBILITY: The gallium 68 dotatate PET is positive. A positive scanwill be defined as at least one lesion with an maximum standardized uptake value (SUVmax) > the average SUV of normal liver. The positive lesion(s) can be in anylocation (bone metastases or visceral metastases). Patients with only bonemetastases will be allowed.

• REGISTRATION ELIGIBILITY: Absolute neutrophil count ≥ 1,500/mcL

• REGISTRATION ELIGIBILITY: Platelets ≥ 100,000/mcL

• REGISTRATION ELIGIBILITY: Hemoglobin ≥ 8 g/dL, prior to each dose of lutetium Lu 177dotatate

• REGISTRATION ELIGIBILITY: Total bilirubin ≤1.5 × institutional upper limit of normal (ULN)

• REGISTRATION ELIGIBILITY: AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN

• REGISTRATION ELIGIBILITY: Creatinine Cockcroft calculated creatinine clearance of ≥ 40 mL/min OR

Exclusion Criteria:

• Patients who are receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to Lutetium Lu 177 dotatate

• As per the Food and Drug Administration (FDA) package insert for Lutetium Lu 177dotatate, use of long-acting somatostatin analogs (e.g., long-acting octreotide) isprohibited within 4 weeks prior to initiating Lutetium Lu 177 dotatate and duringtreatment. Use of short-acting somatostatin analogs is prohibited within 24 hoursprior to initiating Lutetium Lu 177 dotatate and during treatment. Long-actingsomatostatin analogs or short-acting somatostatin analogs will be allowed if thepatient has a history of carcinoid syndrome and requires long-acting or short-actingsomatostatin analogs for the control of his functional syndrome

• Patients with uncontrolled intercurrent illness

• Any of the following within 6 months before starting treatment: stroke, myocardialinfarction, severe/unstable angina pectoris, coronary/peripheral artery bypassgraft; congestive heart failure New York Heart Association (NYHA) Class III or IV

• Uncontrolled hypertension as indicated by a systolic blood pressure >= 160 mmHg ordiastolic blood pressure >= 100 mmHg at screening