Trial Title:
Testing the Addition of Sunitinib Malate to Lutetium Lu 177 Dotatate (Lutathera) in Pancreatic Neuroendocrine Tumors
NCT ID:
NCT05687123
Condition:
Metastatic Pancreatic Neuroendocrine Tumor
Pancreatic Neoplasm
Stage III Pancreatic Neuroendocrine Tumor AJCC v8
Stage IV Pancreatic Neuroendocrine Tumor AJCC v8
Unresectable Pancreatic Neuroendocrine Tumor
Conditions: Official terms:
Neoplasms
Neuroendocrine Tumors
Pancreatic Neoplasms
Adenoma, Islet Cell
Sunitinib
Lutetium Lu 177 dotatate
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo a blood sample collection
Arm group label:
Treatment (sunitinib malate, lutetium Lu 177 dotatate)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo a CT scan
Arm group label:
Treatment (sunitinib malate, lutetium Lu 177 dotatate)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Lutetium Lu 177 Dotatate
Description:
Given IV
Arm group label:
Treatment (sunitinib malate, lutetium Lu 177 dotatate)
Other name:
177 Lu-DOTA-TATE
Other name:
177 Lu-DOTA-Tyr3-Octreotate
Other name:
177Lu-DOTA0-Tyr3-Octreotate
Other name:
Lutathera
Other name:
Lutetium (177Lu) Oxodotreotide
Other name:
Lutetium Lu 177 DOTA(0)-Tyr(3)-Octreotate
Other name:
Lutetium Lu 177-DOTA-Tyr3-Octreotate
Other name:
lutetium Lu 177-DOTATATE
Other name:
Lutetium Oxodotreotide Lu-177
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (sunitinib malate, lutetium Lu 177 dotatate)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo a SSR PET/CT scan
Arm group label:
Treatment (sunitinib malate, lutetium Lu 177 dotatate)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Drug
Intervention name:
Sunitinib Malate
Description:
Given PO
Arm group label:
Treatment (sunitinib malate, lutetium Lu 177 dotatate)
Other name:
SU 011248
Other name:
SU 11248
Other name:
SU-011248
Other name:
SU-11248
Other name:
SU011248
Other name:
SU11248
Other name:
sunitinib
Other name:
Sutent
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.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Comprehensive Cancer Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-826-4673
Email:
becomingapatient@coh.org
Investigator:
Last name:
Daneng Li
Email:
Principal Investigator
Facility:
Name:
Memorial Hospital East
Address:
City:
Shiloh
Zip:
62269
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
314-747-9912
Email:
dschwab@wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at West County Hospital
Address:
City:
Creve Coeur
Zip:
63141
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center-South County
Address:
City:
Saint Louis
Zip:
63129
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Christian Hospital
Address:
City:
Saint Louis
Zip:
63136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Saint Peters Hospital
Address:
City:
Saint Peters
Zip:
63376
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Nikolaos Trikalinos
Email:
Principal Investigator
Facility:
Name:
University Health Network-Princess Margaret Hospital
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
416-946-4501
Email:
clinical.trials@uhn.on.ca
Investigator:
Last name:
Aruz Mesci
Email:
Principal Investigator
Start date:
August 14, 2024
Completion date:
June 14, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05687123
