Trial Title:
AU409 for the Treatment of Advanced Primary Liver Cancers or Solid Tumor With Liver Metastatic Disease
NCT ID:
NCT05791448
Condition:
Advanced Cholangiocarcinoma
Advanced Hepatocellular Carcinoma
Advanced Malignant Solid Neoplasm
Metastatic Malignant Neoplasm in the Liver
Refractory Malignant Solid Neoplasm
Stage III Hepatocellular Carcinoma AJCC v8
Stage IV Hepatocellular Carcinoma AJCC v8
Conditions: Official terms:
Carcinoma
Neoplasms
Carcinoma, Hepatocellular
Liver Neoplasms
Cholangiocarcinoma
Neoplasm Metastasis
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 collection of blood samples
Arm group label:
Treatment (AU409)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (AU409)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
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 (AU409)
Other name:
Magnetic Resonance
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:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Drug
Intervention name:
RNA Transcription Modulator AU-409
Description:
Given PO
Arm group label:
Treatment (AU409)
Other name:
AU 409
Other name:
AU-409
Other name:
AU409
Summary:
This phase I trial tests the safety, side effects, and best dose of a new intervention,
AU409, in treating patients with primary liver cancers that may have spread from where it
first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or
advanced solid tumors that have spread to the liver (liver metastatic disease). AU409 may
stop cancer from growing and spreading. This trial may help researchers determine if
AU409 is safe and effective in treating patients with liver cancers and solid tumors with
liver metastatic disease.
Detailed description:
PRIMARY OBJECTIVES:
I. To determine maximum tolerated dose (MTD) of RNA transcription modulator AU-409
(AU409) and the recommended phase II dose (RP2D).
II. To characterize the safety and tolerability of AU409 by assessing toxicities per
Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 criteria.
SECONDARY OBJECTIVES:
I. To obtain a preliminary assessment of anti-tumor activity of AU409 via objective
radiologic response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
criteria.
II. To determine pharmacokinetics of AU409 in patients with advanced-stage solid tumors.
EXPLORATORY OBJECTIVES:
I. To evaluate the concentration of AU409 in tumor tissue from liver biopsy samples
obtained from a subset of patients treated with AU409 at dose level 4 (300 mg) and above.
II. To evaluate expression of genes with TATA box promotion regions on pre- and post-
treatment liver biopsy samples.
OUTLINE: This is a dose-escalation study.
Patients receive AU409 orally (PO) on study. Patients also undergo computed tomography
(CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the
trial.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age >= 18 years old
- Patients must have histopathologically /cytologically confirmed advanced solid
tumor, which is refractory to standard therapeutic options, or for which there are
no standard therapeutic options. Failure of all approved therapies that have a
marginal impact on survival is not required as long as the treating physician
considers that treatment on study is appropriate for the subject and documents that
the subject elects to defer the approved therapies
- During the dose-escalation portion, patients must have primary liver malignancy
(including hepatocellular carcinoma or cholangiocarcinoma) OR a solid tumor with
liver dominant disease; liver dominant disease is defined as the majority of the
tumor burden being in the liver per investigator assessment AND no more than two
extrahepatic sites of disease (site of disease refers to organ or system). During
the dose expansion portion of the study, eligibility may be limited to one or more
tumor types depending on findings from the dose-escalation phase; this will be
clarified in an amendment
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1
- Patient must have recovered from any toxic effects of previous chemotherapy,
targeted therapy or radiotherapy as judged by the Investigator to =< grade 1 (except
for alopecia). Residual sensory neuropathy =< grade 2 is allowed. Residual endocrine
adverse events (such as hypothyroidism or hypoadrenalism) that are manageable with
replacement therapy are allowed
- Previous chemotherapy/radiotherapy/targeted/immunotherapy therapy should have been
completed at least 4 weeks prior to start of AU409 administration, or five
half-lives, whichever is shorter (except for palliative radiation therapy that
should be completed >= 14 days prior to study entry)
- Patients must have an estimated life expectancy of at least 3 months
- Women of child-bearing potential (WOCBP) and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry, for the duration of study participation. A male participant must agree
to use highly effective contraception during the intervention period and for 60 days
after the last dose of AU409 and refrain from donating sperm during this period.
WOCBP are eligible to participate if they are not pregnant, not breastfeeding, and
agree to follow the contraceptive guidance during the study intervention period and
for at least 90 days after the last dose of AU409
- Should a woman become pregnant or suspect she is pregnant while participating
in this study, she should inform her treating physician immediately
- A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or
has not been naturally postmenopausal for at least 12 consecutive months (i.e., has
had menses at any time in the preceding 12 consecutive months)
- Patients must agree, as part of the informed consent, to undergo liver biopsy (for a
subset of patients enrolled at and above dose level 4) and to provide blood for
pharmacokinetics analysis
- Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 8 g/dL (prior transfusion is allowed if completed 2 weeks prior to
screening and hemoglobin remains >= 8 g/dL)
- For patients with HCC with splenic sequestration: ANC >= 1000/mm^3
- For patients with HCC with splenic sequestration: Platelets >= 70,000
- Calculated clearance >= 60 mL/min/1.73 m^2. Actual body weight should be used for
calculating creatinine clearance (e.g., using the Cockroft-Gault formula). For
subjects with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used
instead
- Total bilirubin =< 1.5 X upper limit of normal (ULN) (subjects with known Gilbert's
hepatic function disease can have bilirubin of up to 2 X ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X ULN; or
AST/ALT =< 5 X ULN if patient has liver tumors
- Prothrombin time (PT)/international normalized ratio (INR) =< 1.8 times upper limit
of normal (unless patient is on anticoagulation)
Exclusion Criteria:
- Patients who have had hypersensitivity to pentamidine or any excipients of AU409
- Treatment with other anticancer therapies (including surgery, radiation therapy,
chemotherapy, anti-angiogenic therapy, targeted therapy, or radiofrequency ablation
therapy, etc.) or investigational therapy within 28 days prior to study entry
(except for palliative radiation therapy that should be completed >= 14 days prior
to study entry)
- Hepatocellular carcinoma patients with a Child Pugh score >= B7
- Patients with known central nervous system metastases which are untreated or
symptomatic; patients with treated brain metastases (completed >= 30 days prior to
screening) are allowed provided they are asymptomatic and are off steroids
- Patient with a history of the following within 6 months prior to cycle 1 day 1: a
myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery
bypass graft, New York Heart Association (NYHA) Class III-IV heart failure,
uncontrolled hypertension, clinically significant cardiac dysrhythmia,
cerebrovascular accident, transient ischemic attack, or seizure disorder. Atrial
fibrillation is allowed if rate is controlled
- Patients who have corrected QT (QTc) interval to > 470 msec (Fredericia's equation)
on 2 out of 3 electrocardiogram (ECG)'s (if first ECG has QTc < 470, no need to
repeat, if first ECG has QTc > 470 repeat twice for a total of 3 ECG's)
- Patients who are on therapeutic anticoagulation with warfarin; however, patients on
therapeutic doses of with low molecular weight heparins or Factor Xa inhibitors are
eligible
- Patient with history of gastrointestinal surgery or malabsorptive conditions that
may change the absorption of drugs and/or cause rapid transit (such as total
gastrectomy, small bowel resection, etc.)
- Patients who have known active hepatitis B. Patients with chronic hepatitis B who
are on anti-viral therapy and have a hepatitis B viral load of =< 500 IU/mL are
allowed on the study. Patients with chronic Hepatitis C are allowed
- Patients who have active infection requiring treatment (except hepatitis B and C as
noted above) including known human immunodeficiency virus (HIV) infection
- Patients who have concurrent conditions resulting in immune compromise, including
chronic treatment with corticosteroids or other immunosuppressive agents
- Patients who have any other condition, including mental illness or substance abuse,
deemed by the Investigator to be likely to interfere with a patient's ability to
sign informed consent, cooperate and participate in the study, or interferes with
the interpretation of the results
- Patients must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants
- Patients who are on medications that are considered to be strong inducers or
inhibitors of the cytochrome P450 isoenzymes should have such medications
discontinued or replaced. Such medications should be avoided for one week prior to
first dose of treatment and during the trial participation. If these medications are
absolutely necessary for the patient and cannot be replaced, enrollment may still be
considered on a case by case basis if it is in the patient's best interest and after
discussion with the principal investigator (PI)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Los Angeles County-USC Medical Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Xiomara Menendez, RN
Phone:
323-865-0212
Email:
Xiomara.Menendez@med.usc.edu
Investigator:
Last name:
Anthony B. El-Khoueiry, MD
Email:
Principal Investigator
Facility:
Name:
USC / Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Xiomara Menendez, RN
Phone:
323-865-0212
Email:
Xiomara.Menendez@med.usc.edu
Investigator:
Last name:
Anthony B. El-Khoueiry, MD
Email:
Principal Investigator
Start date:
March 29, 2023
Completion date:
March 29, 2027
Lead sponsor:
Agency:
University of Southern California
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
Auransa, Inc.
Agency class:
Other
Source:
University of Southern California
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05791448
