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.
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
Patients who have not recovered from acute clinically significant adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
Patients who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate or lutetium Lu 177 dotatate
Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis. Note: Low molecular weight heparin is permitted provided the patient's INR is =< 1.5 and is the preferred anticoagulant in this trial. Other non-coumarin-derivative anticoagulants including direct oral anticoagulants may be used with caution
Single group
Biospecimen Collection
Procedure/SurgeryUndergo a blood sample collection
Computed Tomography
Procedure/SurgeryUndergo a CT scan
Lutetium Lu 177 Dotatate
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo a SSR PET/CT scan
Sunitinib Malate
DrugGiven PO
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
Objective response (ORR)
ORR defined as the percentage of patients who achieve complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. For efficacy data in the expansion cohort, ORR and its 95% confidence interval will be calculated.
Duration of response
The change over-time as well as the difference between sub-groups (i.e., toxicity by Common Terminology Criteria for Adverse Events \[CTCAE\], tumor response by RECIST 1.1, etc.) will be summarized using descriptive statistics and presented graphically.
Progression-free survival (PFS)
The distribution of PFS will be described using Kaplan-Meier product limit methods. The change over-time as well as the difference between sub-groups (i.e., toxicity by CTCAE, tumor response by RECIST 1.1, etc.) will be summarized using descriptive statistics and presented graphically.
Overall survival (OS)
The distribution of OS will be described using Kaplan-Meier product limit methods. The change over-time as well as the difference between sub-groups (i.e., toxicity by CTCAE, tumor response by RECIST 1.1, etc.) will be summarized using descriptive statistics and presented graphically.
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