A Phase II Study of Lutetium Lu 177 Dotatate in Metastatic Prostate Cancer With Neuroendocrine Differentiation
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Metastatic Prostate Adenocarcinoma With Neuroendocrine Differentiation
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 30
- Locations
- 24
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 19 days ago
Overview
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-dotatate 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 at 6 months for patients treated with lutetium Lu 177 dotatate using Prostate Cancer Working Group (PCWG) 3 criteria. SECONDARY 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 receive gallium Ga 68-dotatate IV during screening then 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.
Investigators
Eligibility Criteria
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 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 NOTE: Both patients who have had prior cytotoxic chemotherapy and patients who have never had cytotoxic chemotherapy for prostate cancer will be allowed
- •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
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
Arms & Interventions
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 receive gallium Ga 68-dotatate IV during screening then undergo PET/CT scan at baseline and collection of blood throughout the trial.
Intervention: Biospecimen Collection
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 receive gallium Ga 68-dotatate IV during screening then undergo PET/CT scan at baseline and collection of blood throughout the trial.
Intervention: Computed Tomography
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 receive gallium Ga 68-dotatate IV during screening then undergo PET/CT scan at baseline and collection of blood throughout the trial.
Intervention: Gallium Ga 68-DOTATATE
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 receive gallium Ga 68-dotatate IV during screening then undergo PET/CT scan at baseline and collection of blood throughout the trial.
Intervention: Lutetium Lu 177 Dotatate
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 receive gallium Ga 68-dotatate IV during screening then undergo PET/CT scan at baseline and collection of blood throughout the trial.
Intervention: Positron Emission Tomography
Outcomes
Primary Outcomes
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 Outcomes
- Radiographic progression-free survival (rPFS)(At 6 months)
- Change in FDG-PET signal(Pre-treatment to after 2 doses of lutetium Lu 177 dotatate, assessed up to 16 weeks)
- Treatment response(At 6 months)