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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Undergo a blood sample collection
Undergo a CT scan
Given IV
Undergo MRI
Undergo a SSR PET/CT scan
Given PO
City of Hope Comprehensive Cancer Center
Duarte, California, United States
ACTIVE_NOT_RECRUITINGUCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
RECRUITINGUC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
RECRUITINGMemorial Hospital East
Shiloh, Illinois, United States
RECRUITINGSiteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
RECRUITINGSiteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
RECRUITINGWashington University School of Medicine
St Louis, Missouri, United States
RECRUITINGSiteman Cancer Center-South County
St Louis, Missouri, United States
RECRUITINGSiteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
RECRUITINGUniversity Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
ACTIVE_NOT_RECRUITINGIncidence 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)
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.
Time frame: Up to 4 weeks
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.
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)
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.
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)
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.
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
Intensity of tumor uptake on pre-treatment somatostatin receptor (SSR) positron emission tomography (PET) and post-lutetium Lu 177, as well as the dosimetry imaging. The organ dosimetry will be summarized using descriptive statistics at each time point. The correlation between intensity of tumor uptake on pre-treatment SSR PET and post-lutetium Lu 177, as well as the dosimetry imaging will also be described using Spearman or Pearson correlation coefficient.
Time frame: Up to 4 weeks
Chromogranin A levels
Chromogranin A levels will be measured and chromogranin A responses will be defined as 50% or greater reduction from baseline or normalization per RADIANT-1 study. Chromogranin A levels and responses will be summarized using descriptive statistics. Responses will be correlated with radiographic responses using contingency tables.
Time frame: Up to 4 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.