A Phase I Dose Escalation-Expansion Trial of Sunitinib Malate Plus Lutetium Lu 177 Dotatate (Lutathera) in Somatostatin Receptor Positive Pancreatic Neuroendocrine Tumors
Summary
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
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.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo a blood sample collection
- ProcedureComputed Tomography
Undergo a CT scan
- DrugLutetium Lu 177 Dotatate
Given IV
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- ProcedurePositron Emission Tomography
Undergo a SSR PET/CT scan
- DrugSunitinib Malate
Given PO
Outcome measures
Primary
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
Objective response (ORR)
Time frame: Up to 4 weeks
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
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
Overall survival (OS)
Time frame: From the date of first dose to the date of death by any cause, assessed up to 4 weeks
Intensity of tumor uptake
Time frame: Up to 4 weeks
Chromogranin A levels
Time frame: Up to 4 weeks
Eligibility criteria
Study locations (9)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Memorial Hospital East
Shiloh, Illinois, 62269
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136