Testing the Addition of Sunitinib Malate to Lutetium Lu 177 Dotatate (Lutathera) in Pancreatic Neuroendocrine Tumors
A Phase I Dose Escalation-Expansion Trial of Sunitinib Malate Plus Lutetium Lu 177 Dotatate (Lutathera) in Somatostatin Receptor Positive Pancreatic Neuroendocrine Tumors
4 other identifiers
interventional
24
2 countries
10
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Aug 2024
Typical duration for phase_1
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 14, 2023
CompletedFirst Posted
Study publicly available on registry
January 18, 2023
CompletedStudy Start
First participant enrolled
August 14, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 14, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 14, 2026
April 21, 2026
April 1, 2026
2.3 years
January 14, 2023
April 18, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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
Within the first cycle (8 weeks)
Secondary Outcomes (6)
Objective response (ORR)
Up to 4 weeks
Duration of response
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 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)
From the date of first dose to the date of death by any cause, assessed up to 4 weeks
Intensity of tumor uptake
Up to 4 weeks
- +1 more secondary outcomes
Study Arms (1)
Treatment (sunitinib malate, lutetium Lu 177 dotatate)
EXPERIMENTALPatients 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.
Interventions
Undergo a CT scan
Undergo MRI
Undergo a SSR PET/CT scan
Given PO
Undergo a blood sample collection
Given IV
Eligibility Criteria
You may qualify if:
- 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
- +8 more criteria
You may not qualify if:
- 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
- Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded
- Patients with any of the following conditions are excluded:
- Serious or non-healing wound, ulcer, or bone fracture
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
- Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
- History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry
- History of pulmonary embolism within the past 12 months
- Class III or IV heart failure as defined by the New York Heart Association Class (NYHA) functional classification system
- Patients receiving any medications or substances that are strong CYP3A4 inhibitors within 7 days before dosing, or strong CYP3A4 inducers within 12 days before dosing, are ineligible as sunitinib is a major substrate of CYP3A4. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
- Patients with uncontrolled intercurrent illness
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nikolaos Trikalinos
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 14, 2023
First Posted
January 18, 2023
Study Start
August 14, 2024
Primary Completion (Estimated)
December 14, 2026
Study Completion (Estimated)
December 14, 2026
Last Updated
April 21, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."