Trial Title:
Testing How the Body Responds to the Drug CX-5461 (Pidnarulex) in Patients With Metastatic Solid Cancers
NCT ID:
NCT06606990
Condition:
Metastatic Malignant Solid Neoplasm
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet 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 tissue and blood sample collection
Arm group label:
Treatment (pidnarulex)
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:
Treatment (pidnarulex)
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:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (pidnarulex)
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:
Biological
Intervention name:
Pidnarulex
Description:
Given IV
Arm group label:
Treatment (pidnarulex)
Other name:
CX-5461
Other name:
CX5461
Other name:
Pol I Inhibitor CX5461
Other name:
RNA Pol I Inhibitor CX5461
Summary:
This phase I trial tests the safety, side effects, and best dose of pidnarulex (CX-5461)
in treating patients with solid tumors that has spread from where it first started
(primary site) to other places in the body (metastatic). Pidnarulex is an oral inhibitor
of ribonucleic acid (RNA) polymerase I (Pol I), with potential antineoplastic activity.
It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA)
repair and may kill cancer cells. Giving pidnarulex may be safe, tolerable and/or
effective in treating patients with metastatic solid tumors.
Detailed description:
PRIMARY OBJECTIVE:
I. To assess whether pidnarulex induces a Rad51 response, which will be determined by an
integral biomarker of percentage of cells with Rad51 nuclear foci in tumor biopsy
specimens in patients with and without homologous repair deficiency (HRD) genetic
mutations.
SECONDARY OBJECTIVES:
I. To determine the safety and tolerability of pidnarulex. II. To determine the overall
response rate (complete responses plus partial responses) in patients with advanced,
refractory solid tumors.
III. To measure the pharmacokinetics of pidnarulex. IV. To evaluate other DNA damage and
repair signaling markers including Top2, G4 stabilization, RPA32, pSer33-RPA32, γH2AX,
53BP1, pSer8-RPA32, pKap1m and pNBS1.
EXPLORATORY OBJECTIVES:
I. To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated
with response or resistance.
OUTLINE:
Patients receive pidnarulex intravenously (IV) over 60 minutes on days 1 and 8 of each
cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable
toxicity. Patients also undergo tissue sample collection at baseline and on study,
computed tomography (CT) or magnetic resonance imaging (MRI) and optionally undergo blood
sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically confirmed solid tumors with metastatic disease
that have progressed after ≥ 1 line of prior therapy.
- Patients must have measurable disease as defined by Response Evaluation Criteria in
Solid Tumors (RECIST) version (v) 1.1, with at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest
x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam).
- Patients must have a tumor site amenable to biopsy.
- Age ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky ≥ 70%).
- Absolute neutrophil count ≥ 1,500/mcL.
- Hemoglobin ≥ 9 g/dL.
- Platelets ≥ 100,000/mcL.
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
- (However, patients with known Gilbert disease who have serum bilirubin level of
up to 3 mg/dl may be enrolled.)
- International normalized ratio (INR) or activated partial thromboplastin time
(aPTT).
- Subjects may receive supplementation to meet this eligibility criteria.
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT])
≤ 3.0 x ULN.
- (AST and/or ALT ≤ 5 x ULN for patients with liver involvement.)
- Potassium ≥ lower limit of normal (LLN).
- Subjects may receive supplementation to meet this eligibility criteria.
- Magnesium ≥ LLN.
- Subjects may receive supplementation to meet this eligibility criteria.
- Ionized or corrected calcium ≥ LLN.
- Subjects may receive supplementation to meet this eligibility criteria.
- Creatinine ≤ 1.5 x institutional ULN OR
- Creatinine clearance levels ≥ 60 ml/min based on the Cockcroft-Gault formula.
- Oxygen (O2) saturation > 90% on room air
- Prior therapy completed ≥ 4 weeks or ≥ 5 half-lives of the prior agent (whichever is
shorter) prior to enrollment.
- ≥ 2 weeks since any investigational agent administered (at a sub-therapeutic dose)
as part of a phase 0 study.
- 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.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured.
- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression for ≥
1 month after treatment of the brain metastases.
- 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.
- The effects of pidnarulex on the developing human fetus are unknown. For this
reason, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control or abstinence) 14 days
prior to study entry and for the duration of study participation and for at least 6
months after the last dose of study drug. Should a woman become pregnant or suspect
she is pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately. Women should not breastfeed while taking
pidnarulex and for 6 months after cessation of treatment. Men treated or enrolled on
this protocol must also agree to use adequate contraception 14 days prior to the
study, for the duration of study participation, and 6 months after completion of
pidnarulex administration.
- Willingness to provide blood and biopsy samples for research purposes.
- Ability to understand and the willingness to sign a written informed consent
document. Legally authorized representatives may sign and give informed consent on
behalf of study participants.
Exclusion Criteria:
- Patients must have recovered from clinically-significant adverse-events of their
most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia
or lymphopenia).
- Eligibility of subjects receiving any medications or substances known to affect or
with the potential to affect the activity of pidnarulex will be determined based on
their potential to interact with the CYP3A4 isozyme. Specifically, subjects taking
strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded from
participation in the trial. A list of these excluded medications and substances will
be provided, based on current scientific evidence and recommendations from Senhwa
Biosciences. For medications or substances not listed, or in cases of uncertainty,
the principal investigator may consult with a medical expert or a pharmacologist to
make an informed decision regarding eligibility.
- Treatment with an investigational agent within 30 days prior to the first dose of
study medication.
- History of allergic reactions attributed to inactive ingredients in the drug
product.
- Patients with uncontrolled intercurrent illness or any other significant
condition(s) that would make this protocol unreasonably hazardous.
- Pregnant and lactating women are excluded from this trial. The exclusion is based on
the potential risk of adverse effects of pidnarulex on fetal development and newborn
health. The safety of pidnarulex has not been established in pregnant or lactating
women, and there is a possibility that the drug could cause harm to the developing
fetus or be transferred to the infant through breast milk. Additionally, the
physiological changes that occur during pregnancy and lactation could alter the
pharmacokinetics and pharmacodynamics of pidnarulex, leading to unpredictable drug
exposure and efficacy.
- Patients with chronic, active HBV or HCV infections that require ongoing antiviral
treatment will be excluded from the trial. This exclusion is due to the potential
for drug interactions with the study medication and the risk of exacerbating liver
disease.
- Patients with cirrhosis, regardless of the etiology, will be excluded from
participation in the trial. This is due to the increased risk of complications and
adverse events associated with the study medication in this population.
- Presence of known photosensitivity disorders (xeroderma pigmentosa, porphyria etc.).
Patients who do not agree to use sunglasses and sun blocker (with sun protection
factor 50 [SPF50] to ultraviolet B [UVB] and a high degree of protection against
ultraviolet A [UVA]) if exposed to sunlight during the course of the study and for 3
months after the last dose are not eligible. Patients who plan to use sun beds or
tanning booths during the course of the study and within 3 months after the last
dose are not eligible.
- Active ocular surface disease at baseline (based on ophthalmological evaluation).
- History of cicatricial conjunctivitis (as evaluated by an ophthalmologist).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
December 16, 2024
Completion date:
March 31, 2027
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/NCT06606990
