Trial Title:
Triapine in Combination With Temozolomide for the Treatment of Patients With Recurrent Glioblastoma
NCT ID:
NCT06410248
Condition:
Recurrent Glioblastoma, IDH-Wildtype
Recurrent WHO Grade 2 Glioma
Recurrent WHO Grade 3 Glioma
Recurrent WHO Grade 4 Glioma
Conditions: Official terms:
Glioblastoma
Glioma
Recurrence
Temozolomide
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential 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:
Group 3 (triapine, surgical resection, temozolomide)
Arm group label:
Groups 1 and 2 (temozolomide, triapine)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Group 3 (triapine, surgical resection, temozolomide)
Arm group label:
Groups 1 and 2 (temozolomide, triapine)
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:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Group 3 (triapine, surgical resection, temozolomide)
Arm group label:
Groups 1 and 2 (temozolomide, triapine)
Intervention type:
Procedure
Intervention name:
Resection
Description:
Undergo surgical resection
Arm group label:
Group 3 (triapine, surgical resection, temozolomide)
Other name:
Surgical Resection
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Given PO
Arm group label:
Group 3 (triapine, surgical resection, temozolomide)
Arm group label:
Groups 1 and 2 (temozolomide, triapine)
Other name:
CCRG-81045
Other name:
Gliotem
Other name:
Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
Other name:
M & B 39831
Other name:
M and B 39831
Other name:
Methazolastone
Other name:
RP-46161
Other name:
SCH 52365
Other name:
Temcad
Other name:
Temizole
Other name:
Temodal
Other name:
Temodar
Other name:
Temomedac
Other name:
TMZ
Intervention type:
Drug
Intervention name:
Triapine
Description:
Given PO
Arm group label:
Group 3 (triapine, surgical resection, temozolomide)
Arm group label:
Groups 1 and 2 (temozolomide, triapine)
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 I trial tests the safety, side effects, and best dose of triapine in
combination with temozolomide in treating patients with glioblastoma that has come back
after a period of improvement (recurrent). Triapine inhibits an enzyme responsible for
producing molecules required for the production of deoxyribonucleic acid (DNA), which may
inhibit tumor cell growth. Temozolomide is in a class of medications called alkylating
agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or
stop tumor growth. Giving triapine in combination with temozolomide may be safe,
tolerable, and/or effective in treating patients with recurrent glioblastoma.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the recommended phase 2 dose (RP2D) for triapine (3-AP) in combination
with temozolomide (TMZ).
SECONDARY OBJECTIVES:
I. To evaluate the safety profile of triapine in combination with temozolomide (TMZ).
II. To evaluate progression-free survival (PFS). III. To evaluate overall survival (OS).
IV. To evaluate the overall response rate (ORR) per Response Assessment in Neuro-Oncology
(RANO) criteria.
EXPLORATORY OBJECTIVES:
I. To investigate the distribution of triapine within tumor and peritumoral areas post
oral administration and correlation with serum levels.
II. To investigate the potential interaction of drug absorption when administrating oral
triapine and temozolomide together by measuring plasma levels triapine and temozolomide
post administration.
III. To evaluate oral triapine plasma pharmacokinetics and corresponding methemoglobin
level by venous blood gas proportion.
IV. To evaluate the quality of life per Functional Assessment of Cancer Therapy-Brain
(FACT-Br) for patients treated with triapine and temozolomide.
OUTLINE: This is a dose-escalation study of triapine in combination with temozolomide.
Patients with recurrent glioblastoma not planning to undergo surgery are assigned to
group 1 or group 2. Patients with recurrent glioblastoma planning to undergo surgery are
assigned to group 3.
GROUPS 1 AND 2: Patients receive temozolomide orally (PO) once daily (QD) and triapine PO
QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the
absence of disease progression or unacceptable toxicity. Patients also undergo magnetic
resonance imaging (MRI) at screening and on study and undergo collection of blood samples
on study.
GROUP 3: Patients receive triapine PO QD for 5 days prior to surgical resection. After
surgical resection, patients receive temozolomide PO QD and triapine PO QD on days 1-5 of
each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease
progression or unacceptable toxicity. Patients also undergo MRI at screening and on study
and undergo collection of blood samples on study.
After completion of study treatment, patients are followed up at 30 days and then every 3
months for up to 24 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically confirmed World Health Organization (WHO) grade
2-4 glioma, isocitrate dehydrogenase (IDH) wild type (WT) (by immunohistochemistry
[IHC] R132H negative [neg] or sequencing). Astrocytoma with molecular features of
glioblastoma (GBM). Confirmed diagnosis via molecular testing
- Patients must have an established diagnosis of recurrent glioblastoma and:
- Group 1 and 2: recurrent glioblastoma
- Group 3: Surgically amenable recurrent glioblastoma
- Patients must have stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg
dexamethasone, for ≥ 7 days prior to registration
- Patients with disease that has progressed after a standard or investigational
first-line therapy (e.g. radiotherapy [RT], RT plus temozolomide) with or without
tumor treating fields therapy (TTFields)
- Note: Patients who have received fractionated first-line radiation therapy and
no prior chemotherapy (e.g. as common practice for MGMT unmethylated tumors),
or who have participated in an investigational protocol substituting TMZ for a
novel agent are eligible
- Patients must be able to undergo contrast-enhanced magnetic resonance imaging (MRI)
- Patients must be age ≥ 18 years
- Patients must exhibit a Karnofsky performance status ≥ 70
- Leukocytes (white blood cells [WBC]) ≥ 3,000/mcL
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Hemoglobin (Hgb) ≥ 8 g/dL (transfusion may be used for eligibility outside of 7
days)
- Platelets (PLT) ≥ 100,000/mcL (transfusion or growth factor may be used for
eligibility outside of 7 days)
- Total bilirubin ≤ 2 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
- Creatinine ≤ 1.5 x institutional ULN
- International normalized ratio (INR) ≤ 1.5 x ULN
- Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 x ULN
- 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 of child-bearing potential (POCBP) must agree to use two forms of adequate
contraception (hormonal or barrier method of birth control, abstinence) from time of
informed consent and for the duration of study participation. Patients who can
impregnate their partners must agree to use adequate contraception (hormonal or
barrier method of birth control, abstinence) from time of informed consent and for
the duration of study participation
- Should a patient become pregnant or suspect they are pregnant while they or
their partner is participating in this study, they should inform their treating
physician immediately.
- Note: At the discretion of the investigator, acceptable methods of
contraception may include total abstinence in cases where the lifestyle of the
patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation,
symptothermal, postovulation methods] and withdrawal are not acceptable methods
of contraception.)
- Note: A POCBP is any person with an egg-producing reproductive tract
(regardless of gender, sexual orientation, having undergone a tubal ligation,
or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy, bilateral salpingectomy, or bilateral
oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and
therefore has not been naturally postmenopausal for > 12 months) (in
patients > 45 years of age in the absence of other biological or
physiological causes)
- Potential POCBP who may be menopausal and are < 55 years of age must
have a serum follicle-stimulating hormone (FSH) level > 40 mIU/mL to
confirm menopause
- Note: Documentation may include review of medical records, medical
examination, or medical history interview by study site staff
- Patient must be willing and able to comply with the protocol for the duration of the
study and provide written, signed, and dated informed consent prior to study
registration.
- NOTE: No study-specific screening procedures may be performed until written
consent has been obtained
- Patients must have the ability to understand and the willingness to sign a written
informed consent document
Exclusion Criteria:
- Patients who have a prior or concurrent malignancy that may interfere with study
treatment or safety
- NOTE: 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, per principal
investigator (PI) discretion
- Patients who are receiving any other investigational agents.
- Exceptions: COVID-19 vaccine and treatment is allowed, per PI's discretion
- Patient's interval since last cytotoxic therapy ≥ 1 cycle or ≥ 2 biological
half-lives, i.e.
- ≥ 28 days since start of last cycle of temozolomide (cycle length-28 days)
- ≥ 42 days since start of last cycle of lomustine or other nitrosourea (cycle
length-42 days)
- ≥ 21 days since start of last cycle of a small molecule targeted agent (cycle
length-21 days)
- ≥ 42 days from last bevacizumab infusion (cycle length-42 days)
- Patients who have a history of allergic reactions attributed to compounds of similar
chemical composition to temozolomide or triapine
- Patients with spinal cord and diffuse leptomeningeal dissemination
- Patients with a history of G6PD deficiency or other congenital or autoimmune
hemolytic disorders. All participants will be screened for G6PD levels prior to
registration
- Patients who have an uncontrolled intercurrent illness including, but not limited to
any of the following:
- Have uncontrolled epilepsy
- Have an uncontrolled intercurrent illness
- Are pregnant or nursing
- Concurrent malignancy (outside of glioblastoma) that requires tumor directed
treatment
- Known concurrent shingles, herpes, cytomegalovirus (CMV) infection
- Known concurrent opportunistic fungal infection
- Known immunodeficiency that could lead to opportunistic infections
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Any other illness or condition that the treating investigator feels would
interfere with study compliance or would compromise the patient's safety or
study endpoints
- Patients who are pregnant or nursing. Pregnant patients are excluded from this study
because temozolomide is an alkylating agent with 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 temozolomide,
breastfeeding should be discontinued if the mother is treated with temozolomide
- Patients who are unable to swallow oral medication or have problems/diseases that
affect absorption or oral medication
- Patients with a known history of human immunodeficiency virus (HIV), hepatitis B
virus (HBV), and/or hepatitis C virus (HCV). If patient does not have a known
history testing will not be conducted
- Note: Temozolomide is an immunosuppressive agent. Patients with a known history
of HIV, HBV, and HCV, and unexplained opportunistic infections are not eligible
due to safety reasons
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Start date:
July 23, 2024
Completion date:
May 12, 2030
Lead sponsor:
Agency:
Northwestern University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
BrainUp Inc
Agency class:
Other
Source:
Northwestern University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06410248
