Trial Title:
Testing the Effectiveness of an Anti-cancer Drug, Triapine, When Used With Targeted Radiation-based Treatment (Lutetium Lu 177 Dotatate), Compared to Lutetium Lu 177 Dotatate Alone for Metastatic Neuroendocrine Tumors
NCT ID:
NCT05724108
Condition:
Metastatic Neuroendocrine Tumor
Conditions: Official terms:
Neuroendocrine Tumors
Lutetium Lu 177 dotatate
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Arm 1 (triapine, lutetium Lu 177 dotatate)
Arm group label:
Arm 2 (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 CT
Arm group label:
Arm 1 (triapine, lutetium Lu 177 dotatate)
Arm group label:
Arm 2 (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:
Arm 1 (triapine, lutetium Lu 177 dotatate)
Arm group label:
Arm 2 (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:
Arm 1 (triapine, lutetium Lu 177 dotatate)
Arm group label:
Arm 2 (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:
Drug
Intervention name:
Triapine
Description:
Given PO
Arm group label:
Arm 1 (triapine, lutetium Lu 177 dotatate)
Other name:
3-aminopyridine-2-carboxaldehyde thiosemicarbazone
Other name:
3-AP
Other name:
3-Apct
Other name:
OCX-0191
Other name:
OCX-191
Other name:
OCX191
Other name:
PAN-811
Summary:
This phase II trial compares the effect of adding triapine to lutetium Lu 177 dotatate
versus lutetium Lu 177 dotatate alone (standard therapy) in shrinking tumors or slowing
tumor growth in patients with neuroendocrine tumors that have spread from where they
first started (primary site) to other places in the body (metastatic). Triapine may stop
the growth of tumor cells by blocking some of the enzymes needed for deoxyribonucleic
acid synthesis and cell growth. Lutetium Lu 177 dotatate is a radioactive drug. It binds
to a protein called somatostatin receptor, which is found on some neuroendocrine tumor
cells. Lutetium Lu 177 dotatate builds up in these cells and gives off radiation that may
kill them. It is a type of radioconjugate and a type of somatostatin analog. Giving
triapine in combination with lutetium Lu 177 dotatate may be more effective at shrinking
tumors or slowing tumor growth in patients with metastatic neuroendocrine tumors than the
standard therapy of lutetium Lu 177 dotatate alone.
Detailed description:
PRIMARY OBJECTIVE:
I. Evaluate the overall response rate (ORR) by Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 of combination triapine + lutetium Lu 177 dotatate (treatment arm 1)
versus standard of care lutetium Lu 177 dotatate alone (treatment arm 2).
SECONDARY OBJECTIVE:
I. Evaluate progression-free survival (PFS) between the two treatment arms (combination
arm 1 versus standard of care arm 2).
EXPLORATORY OBJECTIVES:
I. Evaluate plasma hPG80 as a biomarker of treatment response. II. Evaluate plasma
deoxyribonucleosides as a biomarker of triapine resistance. III. Collect plasma for
circulating deoxyribonucleic acid (DNA) (ctDNA) assessment.
IV. Evaluate triapine plasma pharmacokinetics (PK) in the combination arm (treatment arm
1 only).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive triapine orally (PO) on days 1-14 of each cycle and lutetium Lu
177 dotatate intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat
every 8 weeks for 4 cycles in the absence of disease progression or unacceptable
toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance
imaging (MRI) and collection of blood samples throughout the trial.
ARM 2: Patients receive lutetium Lu 177 dotatate IV over 30 minutes on day 1 of each
cycle. Cycles repeat every 8 weeks for 4 cycles in the absence of disease progression or
unacceptable toxicity. Patients also undergo CT and/or MRI and collection of blood
samples throughout the trial.
After completion of study treatment, patients are followed up at 8 and 12 months, then
every 6 months for 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have metastatic, histologically confirmed well-differentiated
neuroendocrine tumor with positive gallium 68 DOTATATE or copper 64 DOTATATE scan.
Lesions on dotatate scan will be considered positive if the standardized uptake
volume maximum (SUVmax) of target lesion is > 2 times standardized uptake value
(SUV) mean of normal liver parenchyma. Patients with lung neuroendocrine tumors
(NETs) are excluded from the trial
- Patients must have progressive disease based on RECIST criteria, version 1.1
evidenced with CT scans/MRI obtained within 24 months from enrollment
- Patients must have measurable disease per RECIST 1.1
- Failure of at least one prior systemic cancer treatment with somatostatin analogs
- No prior exposure to peptide receptor radionuclide therapy
- Recovered from adverse events of previously administered therapeutic agents (i.e.,
to grade 2 or less toxicity) according to Common Terminology Criteria for Adverse
Events (CTCAE) 5.0
- Age >= 18 years
- Because no dosing or adverse event data are currently available on the use of
triapine 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 >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 3 x institutional ULN
- Serum creatinine =< 1.5 x institutional ULN. Creatinine > 1.5 ULN will require a
measured creatinine clearance (CrCl) > 50 ml/min to qualify
- Hemoglobin > 5.0 mmol/L (> 8.0 g/dL)
- 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 and off steroids are eligible if follow-up
brain imaging after central nervous system (CNS)-directed therapy shows no evidence
of progression for at least 4 weeks prior to enrollment in the study. Patients with
a history of brain metastases must have a head CT with contrast to document stable
disease prior to enrollment in the study
- 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
- 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
- Pregnancy precaution: Men and women should avoid pregnancy for seven months after
the date of their last treatment with lutetium Lu 177 dotatate. It is noteworthy
that beta-human chorionic gonadotropin (beta-HCG) may be secreted by a small
percentage of NETs, such that, in addition to being a pregnancy marker, it also is a
tumor marker. Consequently, NET female patients with positive beta-HCG (> 5 mIU/mL)
at baseline can be eligible to enter the study and receive treatment if pregnancy
can be excluded by lack of expected doubling of beta-HCG and negative pelvic
ultrasound. Normally, in pregnant subjects beta-HCG doubles every 2 days during the
first 4 weeks of pregnancy and every 3.5 days by weeks 6 to 7. Women of childbearing
potential include any female who has experienced menarche and who has not undergone
successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
bilateral ovariectomy) or is not postmenopausal (defined as amenorrhea > 12
consecutive months, and for women on hormone replacement therapy, only with a
documented plasma follicle-stimulating hormone [FSH] level > 35 mIU/mL). Even women
who are using oral, implanted, or injected contraceptive hormones, an intrauterine
device (IUD), or barrier methods (diaphragm, condoms, spermicidal) to prevent
pregnancy, are practicing abstinence or where the partner is sterile (e.g.,
vasectomy) should be considered to be of childbearing potential. Postmenopausal
women who have fertilized eggs implanted are also considered to be of childbearing
potential. Acceptable methods of contraception may include total abstinence at the
discretion of the Investigator in cases where the age, career, lifestyle, or sexual
orientation of the patient ensures compliance. Periodic abstinence (e.g., calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception. Reliable contraception (hormonal or barrier method of
birth control; abstinence) should be maintained throughout the study and for 7
months after study treatment discontinuation. All men and women of childbearing
potential and male partners must use a double-barrier method of birth control or
practice continuous abstinence from heterosexual contact throughout the study and
for seven months after the end of the last treatment
- Ability to understand and the willingness to sign a written informed consent
document
Exclusion Criteria:
- Patients who have not recovered from adverse events of previously administered
therapeutic agents (i.e., have residual toxicities > grade 2) according to CTCAE
5.0, 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 triapine or lutetium Lu 177 dotatate
- Patients with uncontrolled intercurrent illness
- Uncontrolled congestive heart failure (New York Heart Association [NYHA] III, IV)
- Pregnant women are excluded from this study because triapine is a ribonucleotide
reductase (RNR) inhibitor 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 triapine and lutetium Lu 177 dotatate,
breastfeeding should be discontinued if the mother is treated with triapine and
lutetium Lu 177 dotatate and for 2.5 months following the last treatment
- Inability to swallow oral medications or gastrointestinal disease limiting
absorption of oral agents
- Patients with any other significant condition, currently uncontrolled by treatment,
which may interfere with completion of the study
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:
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Address:
City:
Irvine
Zip:
92612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Farshid Dayyani
Email:
Principal Investigator
Facility:
Name:
UC Irvine Health/Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Farshid Dayyani
Email:
Principal Investigator
Facility:
Name:
University of California Davis Comprehensive Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
916-734-3089
Investigator:
Last name:
Edward J. Kim
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Aventura
Address:
City:
Aventura
Zip:
33180
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
954-461-2180
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Coral Gables
Address:
City:
Coral Gables
Zip:
33146
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Address:
City:
Deerfield Beach
Zip:
33442
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
University of Florida Health Science Center - Gainesville
Address:
City:
Gainesville
Zip:
32610
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
352-273-8010
Email:
cancer-center@ufl.edu
Investigator:
Last name:
Kathryn E. Hitchcock
Email:
Principal Investigator
Facility:
Name:
University of Miami Miller School of Medicine-Sylvester Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Kendall
Address:
City:
Miami
Zip:
33176
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Plantation
Address:
City:
Plantation
Zip:
33324
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Aman Chauhan
Email:
Principal Investigator
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
312-695-1301
Email:
cancer@northwestern.edu
Investigator:
Last name:
Al B. Benson
Email:
Principal Investigator
Facility:
Name:
University of Kentucky/Markey Cancer Center
Address:
City:
Lexington
Zip:
40536
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
859-257-3379
Investigator:
Last name:
Lowell B. Anthony
Email:
Principal Investigator
Facility:
Name:
Rutgers Cancer Institute of New Jersey
Address:
City:
New Brunswick
Zip:
08903
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
732-235-7356
Investigator:
Last name:
Matthew P. Deek
Email:
Principal Investigator
Facility:
Name:
NYP/Weill Cornell Medical Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-746-1848
Investigator:
Last name:
Elizabeta C. Popa
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center LAO
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lowell B. Anthony
Email:
lowell.anthony@uky.edu
Investigator:
Last name:
Lowell B. Anthony
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-293-5066
Email:
Jamesline@osumc.edu
Investigator:
Last name:
Bhavana Konda
Email:
Principal Investigator
Facility:
Name:
University of Pittsburgh Cancer Institute (UPCI)
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
412-647-8073
Investigator:
Last name:
Janie Y. Zhang
Email:
Principal Investigator
Facility:
Name:
MD Anderson in The Woodlands
Address:
City:
Conroe
Zip:
77384
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
866-632-6789
Email:
askmdanderson@mdanderson.org
Investigator:
Last name:
James C. Yao
Email:
Principal Investigator
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-632-6789
Email:
askmdanderson@mdanderson.org
Investigator:
Last name:
James C. Yao
Email:
Principal Investigator
Facility:
Name:
MD Anderson West Houston
Address:
City:
Houston
Zip:
77079
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-632-6789
Email:
askmdanderson@mdanderson.org
Investigator:
Last name:
James C. Yao
Email:
Principal Investigator
Facility:
Name:
MD Anderson League City
Address:
City:
League City
Zip:
77573
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-632-6789
Email:
askmdanderson@mdanderson.org
Investigator:
Last name:
James C. Yao
Email:
Principal Investigator
Facility:
Name:
MD Anderson in Sugar Land
Address:
City:
Sugar Land
Zip:
77478
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-632-6789
Email:
askmdanderson@mdanderson.org
Investigator:
Last name:
James C. Yao
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute/University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-424-2100
Email:
cancerinfo@hci.utah.edu
Investigator:
Last name:
Heloisa P. Soares
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Address:
City:
Madison
Zip:
53718
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-622-8922
Email:
clinicaltrials@cancer.wisc.edu
Investigator:
Last name:
Sam J. Lubner
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center - University Hospital
Address:
City:
Madison
Zip:
53792
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-622-8922
Email:
clinicaltrials@cancer.wisc.edu
Investigator:
Last name:
Sam J. Lubner
Email:
Principal Investigator
Start date:
August 30, 2023
Completion date:
January 1, 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/NCT05724108
