AU409 for the Treatment of Advanced Primary Liver Cancers or Solid Tumor With Liver Metastatic Disease
First in Human Dose Escalation Study of AU409 in Patients With Advanced Primary Liver Cancers or Advanced Solid Tumor With Liver Predominant Metastatic Disease
3 other identifiers
interventional
36
1 country
2
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Mar 2023
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 6, 2023
CompletedStudy Start
First participant enrolled
March 29, 2023
CompletedFirst Posted
Study publicly available on registry
March 30, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 29, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 29, 2028
June 1, 2026
May 1, 2026
4 years
March 6, 2023
May 29, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Maximum Tolerated Dose
MTD is defined as the highest dose tested at which none or no more than one patient experienced DLT attributable to the study drug(s), when 6 patients were treated at that dose and are evaluable for toxicity. The MTD is one dose level below the lowest dose tested in which 2 or more patients experienced DLT attributable to the study drug(s.)
Up to 28 days
Recommended phase II dose
The RP2D for evaluation in Phase 2 will be selected based on overall safety and tolerability, PK, preliminary efficacy, and estimates of efficacious liver exposures extrapolated from nonclinical data and Phase 1 of the study. The RP2D may or may not be the same as the MTD identified in Phase 1. For example, if the MTD was not reached with a plateau of exposures despite increasing drug dose, or if exposure at the MTD was much higher than the level expected to be required for efficacy, or if subsequent cycles of treatment provided additional insight on the safety profile, then the RP2D might be different, though not higher dose than the MTD. Additionally, if an MTD is not identified in the dose range expected, a dose that met the tolerability and PK criteria could be selected as the RP2D.
Up to 28 days
Incidence of adverse events
Will be assessed per Common Terminology Criteria for Adverse Events version 5.0 criteria.
Up to 30 days after removal from treatment or until death, whichever occurs first
Secondary Outcomes (3)
Objective radiologic response
Up 3 years
Pharmacokinetics evaluation - Peak plasma concentration (Cmax)
Day 1 of cycles 1 and 2. Days 8, 15, and 21 of cycle 1. (cycle = 28 days)
Pharmacokinetics evaluation - Peak time (Tmax)
Day 1 of cycles 1 and 2. Days 8, 15, and 21 of cycle 1. (Cycle = 28 days)
Study Arms (1)
Treatment (AU409)
EXPERIMENTALPatients receive AU409 PO on study. Patients also undergo CT or MRI and collection of blood samples throughout the trial.
Interventions
Undergo collection of blood samples
Undergo CT scan
Undergo MRI
Eligibility Criteria
You may qualify if:
- 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
- +5 more criteria
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Southern Californialead
- National Cancer Institute (NCI)collaborator
- Auransa, Inc.collaborator
Study Sites (2)
Los Angeles County-USC Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anthony B El-Khoueiry, MD
University of Southern California
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 6, 2023
First Posted
March 30, 2023
Study Start
March 29, 2023
Primary Completion (Estimated)
March 29, 2027
Study Completion (Estimated)
March 29, 2028
Last Updated
June 1, 2026
Record last verified: 2026-05