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

NCT ID: NCT05687123

Last Updated: 2026-02-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-14
• Study Completion Date: 2026-12-14

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.

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.

Conditions

Metastatic Pancreatic Neuroendocrine Tumor; Pancreatic Neoplasm; Stage III Pancreatic Neuroendocrine Tumor AJCC v8; Stage IV Pancreatic Neuroendocrine Tumor AJCC v8; Unresectable Pancreatic Neuroendocrine Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (sunitinib malate, lutetium Lu 177 dotatate)

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.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo a blood sample collection

Computed Tomography

Intervention Type: PROCEDURE

Undergo a CT scan

Lutetium Lu 177 Dotatate

Intervention Type: DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo a SSR PET/CT scan

Sunitinib Malate

Intervention Type: DRUG

Given PO

Interventions

Biospecimen Collection

Undergo a blood sample collection

Intervention Type: PROCEDURE

Computed Tomography

Undergo a CT scan

Intervention Type: PROCEDURE

Lutetium Lu 177 Dotatate

Given IV

Intervention Type: DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Positron Emission Tomography

Undergo a SSR PET/CT scan

Intervention Type: PROCEDURE

Sunitinib Malate

Given PO

Intervention Type: DRUG

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; tomography; 177 Lu-DOTA-TATE; 177 Lu-DOTA-Tyr3-Octreotate; 177Lu-DOTA0-Tyr3-Octreotate; Lutathera; Lutetium (177Lu) Oxodotreotide; Lutetium Lu 177 DOTA(0)-Tyr(3)-Octreotate; Lutetium Lu 177-DOTA-Tyr3-Octreotate; lutetium Lu 177-DOTATATE; Lutetium Oxodotreotide Lu-177; Magnetic Resonance; Magnetic Resonance Imaging (MRI); Magnetic resonance imaging (procedure); Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI; MRI Scan; MRIs; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Structural MRI; Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron emission tomography (procedure); Positron Emission Tomography Scan; Positron-Emission Tomography; PT; SU 011248; SU 11248; SU-011248; SU-11248; SU011248; SU11248; sunitinib; Sutent

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically or cytologically confirmed metastatic, unresectable well- or moderately-differentiated pancreatic neuroendocrine tumors (PNETs) of any grade
• Patients with measurable disease appropriate for lutetium Lu 177 dotatate treatment as determined by positive screening with SSR PET/CT
• Patients may have disease progression on or intolerance of up to one line of systemic therapy other than somatostatin analog therapy. Prior and/or concurrent use of somatostatin analogs are allowed
• Patients who 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
• 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
• Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted prior to study entry, provided that the average of three BP readings at a visit prior to enrollment is less than 140/90 mmHg
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression, as determined by a repeat imaging study at least 4 weeks following the completion of treatment. Patients with treated brain metastases must also be off steroids for at least 1 month and stable
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• The effects of lutetium Lu 177 dotatate and sunitinib malate on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because radionucleotides and anti-angiogenic agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. All women of childbearing potential must have a negative pregnancy test prior to receiving sunitinib malate. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of lutetium Lu 177 dotatate and sunitinib malate administration

Exclusion Criteria

• 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 prothrombin time (PT) international normalized ratio (INR) is =< 1.5
• 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
• Pregnant women are excluded from this study because sunitinib malate is an anti-angiogenic agent and lutetium Lu 177 dotatate is a peptide receptor radionuclide therapy with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sunitinib malate and lutetium Lu 177 dotatate, breastfeeding should be discontinued if the mother is treated with sunitinib malate and lutetium Lu 177 dotatate. Breastfeeding should be discontinued for 2.5 months following the last lutetium Lu 177 dotatate treatment. These potential risks may also apply to other agents used in this study
• Patients who have had prior treatment with sunitinib malate or lutetium Lu 177 dotatate therapy or other radiopharmaceuticals (including, but not limited to, metaiodobenzylguanidine [MIBG], yttrium-90 [Y-90], radioactive iodide [RAI]), as MIBG and RAI could potentially increase risk of myelodysplastic syndrome or irreversible hematologic toxicities
• Patients with left ventricular ejection fraction of 50% or less

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nikolaos Trikalinos

Role: PRINCIPAL_INVESTIGATOR

Yale University Cancer Center LAO

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status: ACTIVE_NOT_RECRUITING

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, United States

Site Status: RECRUITING

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status: RECRUITING

Memorial Hospital East

Shiloh, Illinois, United States

Site Status: RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Site Status: RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Site Status: RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status: RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, United States

Site Status: RECRUITING

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, United States

Site Status: RECRUITING

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States; Canada

Facility Contacts

Site Public Contact

Role: primary

ucstudy@uci.edu

877-827-8839

Site Public Contact

Role: primary

ucstudy@uci.edu

877-827-8839

Site Public Contact

Role: primary

dschwab@wustl.edu

314-747-9912

Site Public Contact

Role: primary

info@siteman.wustl.edu

800-600-3606

Site Public Contact

Role: primary

info@siteman.wustl.edu

800-600-3606

Site Public Contact

Role: primary

info@siteman.wustl.edu

800-600-3606

Site Public Contact

Role: primary

info@siteman.wustl.edu

800-600-3606

Site Public Contact

Role: primary

info@siteman.wustl.edu

800-600-3606

Other Identifiers

NCI-2022-09321

Identifier Type: REGISTRY

Identifier Source: secondary_id

10479

Identifier Type: OTHER

Identifier Source: secondary_id

10479

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA186689

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2022-09321

Identifier Type: -

Identifier Source: org_study_id