Overview

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

Status:
Not yet recruiting
Trial end date:
2024-11-01
Target enrollment:
0
Participant gender:
All
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 dotate 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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Treatments:
Lutetium Lu 177 dotatate
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