Testing the Addition of Sunitinib Malate to Lutetium Lu 177 Dotatate (Lutathera) in Pancreatic Neuroendocrine Tumors

Brief summary public domain (ClinicalTrials.gov)

This phase I trial tests the safety, side effects, and best dose of sunitinib malate in combination with lutetium Lu 177 dotatate in treating patients with pancreatic neuroendocrine tumors. Sunitinib malate is in a class of medications called kinase inhibitors and a form of targeted therapy that blocks the action of abnormal proteins called VEGFRs that signal tumor cells to multiply. This helps stop or slow the spread of tumor cells. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and not harm normal cells. It is also a form of targeted therapy because it works by attaching itself to specific molecules (receptors) on the surface of tumor cells, known as somatostatin receptors, so that radiation can be delivered directly to the tumor cells and kill them. Giving sunitinib malate and lutetium Lu 177 dotatate in combination may be safer and more effective in treating pancreatic neuroendocrine tumors than giving either drug alone.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVE: I. To evaluate the safety and maximum tolerated dose (MTD) for the combination of sunitinib malate with lutetium Lu 177 dotatate in metastatic unresectable pancreatic neuroendocrine tumors (NETS). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To assess objective response rate (ORR) of the combination by the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. III. To assess progression-free survival (PFS) and overall survival (OS) of the combination. IV. To determine the duration of response (DOR) from the combination. V. To determine lutetium Lu 177 dotatate dosimetry in the combination. VI. To associate somatostatin receptor (SSR) positron emission tomography (PET) triage imaging with lutetium Lu 177 dotatate dosimetry. VII. To assess the correlation of chromogranin A (CgA) with disease response in patients being treated with lutetium Lu 177 dotatate. OUTLINE: This is a dose-escalation study of sunitinib malate followed by a dose-expansion study. Patients receive sunitinib malate orally (PO) daily (QD) from day 1 of lutetium 177 dotatate therapy to 28 days after the last dose of lutetium 177 dotatate in the absence of unacceptable toxicity. Patients also receive lutetium Lu 177 dotatate intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 8 weeks (Q8W) for 4 cycles in the absence of unacceptable toxicity. Patients undergo a computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Patients also undergo a SSR PET/CT scan during screening and blood sample collection on study. After completion of study treatment, patients are followed for up to 4 weeks.

Intervention public domain (ClinicalTrials.gov)

Procedure: Biospecimen Collection. Undergo a blood sample collection

Intervention public domain (ClinicalTrials.gov)

Procedure: Computed Tomography. Undergo a CT scan

Intervention public domain (ClinicalTrials.gov)

Drug: Lutetium Lu 177 Dotatate. Given IV

Intervention public domain (ClinicalTrials.gov)

Procedure: Magnetic Resonance Imaging. Undergo MRI

Intervention public domain (ClinicalTrials.gov)

Procedure: Positron Emission Tomography. Undergo a SSR PET/CT scan

Intervention public domain (ClinicalTrials.gov)

Drug: Sunitinib Malate. Given PO

Arm public domain (ClinicalTrials.gov)

Treatment (sunitinib malate, lutetium Lu 177 dotatate) (experimental): Patients receive sunitinib malate PO QD from day 1 of lutetium 177 dotatate therapy to 28 days after the last dose of lutetium 177 dotatate in the absence of unacceptable toxicity. Patients also receive lutetium Lu 177 dotatate IV over 30 minutes on day 1 of each cycle. Cycles repeat Q8W for 4 cycles in the absence of unacceptable toxicity. Patients undergo a CT scan and/or MRI throughout the trial. Patients also undergo a SSR PET/CT scan during screening and blood sample collection on study.

Primary outcome public domain (ClinicalTrials.gov)

Incidence of adverse events (AEs). Dose-limiting toxicities (DLTs) during the first 8 weeks of the combination of sunitinib malate plus lutetium Lu 177 dotatate and incidence of treatment-emergent AEs during DLT observation period. DLTs will be defined as grade 3 or worse hematologic and non-hematologic toxicity that is considered clinically significant and at least possibly related to lutetium Lu 177 dotatate and sunitinib malate within the first cycle (8 weeks). Safety endpoints will be listed for each dose level and the tabulations of adverse events will also be produced by severity and by relationship to study drug Time frame: Within the first cycle (8 weeks).

Secondary outcome public domain (ClinicalTrials.gov)

Objective response (ORR). Time frame: Up to 4 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Duration of response. Time frame: The time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST v1.1, assessed up to 4 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Progression-free survival (PFS). Time frame: The time from first dose to the earlier date of assessment of progression or death by any cause, assessed up to 4 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival (OS). Time frame: From the date of first dose to the date of death by any cause, assessed up to 4 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Intensity of tumor uptake. Time frame: Up to 4 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Chromogranin A levels. Time frame: Up to 4 weeks.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Patients must have histologically or cytologically confirmed metastatic or unresectable well- or moderately-differentiated pancreatic neuroendocrine tumors (PNETs) of all grades (Grade 1, grade 2 and grade 3) * Patients with measurable disease per RECIST 1.1 appropriate for lutetium Lu 177 dotatate treatment, as determined by positive screening with SSR PET/CT and appropriate theranostics consultation (nuclear medicine or radiation oncology consultation) * Patients may be treatment naïve or have disease progression on or intolerance of up to one line of systemic therapy other than somatostatin analog therapy (somatostatin analog therapy is not considered a line of systemic therapy). Systemic therapy is considered therapy for unresectable or metastatic disease. Any prior adjuvant therapy with curative intent will not be considered a line unless relapse occurs within 6 months. Prior and/or concurrent use of somatostatin analogs are allowed * Patients who have have received a prior line of therapy must have documented disease progression per RECIST 1.1 within 12 months of initiation of the study protocol * Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of sunitinib malate in combination with lutetium Lu 177 dotatate in patients \< 18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * Absolute neutrophil count \>= 1,000/mcL * Platelets \>= 75,000/mcL * Total bilirubin =\< 1.5 institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 × institutional ULN * Creatinine clearance \> 50 ml/min OR Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 * Hemoglobin \> 8.0 g/dL * White blood cell count \> 2000/mL * Serum calcium =\< 12.0 mg/dL * International normalized ratio (INR) =\< 1.5 * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better and have left ventricular ejection fraction of 50% or more. (Patients with no known history and no current symptoms of cardiac disease do not require left …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 24 participants (estimated).