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.
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
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
Single group
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Computed Tomography
Procedure/SurgeryUndergo CT scan
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
RNA Transcription Modulator AU-409
DrugGiven PO
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.)
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.
Incidence of adverse events
Will be assessed per Common Terminology Criteria for Adverse Events version 5.0 criteria.
Objective radiologic response
Will assess preliminary assessment of anti-tumor activity of AU409 via objective radiologic response using Response Evaluation Criteria in Solid Tumors 1.1 criteria.
Pharmacokinetics evaluation - Peak plasma concentration (Cmax)
Pharmacokinetics profile will be evaluated following a comprehensive PK parameter
Pharmacokinetics evaluation - Peak time (Tmax)
Pharmacokinetics profile will be evaluated following comprehensive PK parameter
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University of Southern California
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Auransa, Inc.
Collaborator
