P3, N=30, Active, not recruiting, Icahn School of Medicine at Mount Sinai | Recruiting --> Active, not recruiting

P3, N=30, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Oct 2024 --> Jul 2025 | Trial primary completion date: Oct 2024 --> Jul 2025

In the HOME0-grown organoids, IL-13 and UAB30 induced epithelial changes reminiscent of basal cell hyperplasia, a common histopathologic feature in broad esophageal disease conditions including eosinophilic esophagitis. HOME0 allows modeling of the homeostatic differentiation gradient and perturbation of the human esophageal epithelium while permitting a comparison of organoids from mice and other organs grown in ADF-based media.

P3, N=21, Completed, Austin Institute for Clinical Research | Recruiting --> Completed | N=40 --> 21

P1, N=27, Terminated, National Cancer Institute (NCI) | N=39 --> 27 | Active, not recruiting --> Terminated; Inadequate Accrual Rate

P1, N=12, Suspended, Io Therapeutics | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Jul 2023 --> Dec 2024

P1/2, N=0, Withdrawn, University of Alabama at Birmingham | N=84 --> 0 | Trial completion date: Aug 2025 --> Aug 2023 | Recruiting --> Withdrawn | Trial primary completion date: Aug 2024 --> Aug 2023

These data demonstrate a novel use of the RXR agonist, IRX4204, to delay the formation of Brca1-deficient mammary tumors. We have found that IRX4204 treatment modulates the tumor immune response through increased infiltration of cytotoxic CD8-positive T-cells in Brca1-deficient mammary tumors in vivo. We have also determined that IRX4204 modulates lipid metabolism in breast cancer cell lines in vitro.

P3, N=30, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

Background Bexarotene and 9cUAB30 are oral retinoid X receptor (RXR) agonists which inhibit proliferation in breast cancer. There was no evidence by IHC of antigen expression loss with sequential RXR agonist with the vaccine. Conclusions The RXR agonists have an immunostimulatory role with plasmid cancer vaccines, but further modification of the immune environment may be needed for prevention vaccines.

P1/2, N=84, Recruiting, University of Alabama at Birmingham | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2023 --> Aug 2024

LyP treatment options include topical steroids, topical bexarotene, phototherapy, nitrogen mustard, methotrexate, and intralesional interferon. In our patient, the papules and ulcerated plaques regressed under treatment with methotrexate

On the other hand, nuclear factor-κB (NF-κB) inhibitors such as pyrrolidine dithiocarbamate (50 μM) and Bay11-7082 (10 μM) prevented thrombin-induced shrinkage of the striatal region...We also found that daily administration of peretinoin reduced histopathological injury and alleviated motor deficits in a mouse model of intracerebral hemorrhage. These results indicate that NR1B agonists including peretinoin may serve as a therapeutic option for hemorrhagic brain injury.

P1, N=39, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2023 --> Jun 2024

Notably, MSU-42011 and selumetinib alone similarly inhibited CCL2 mRNA expression by 25% in THP1 macrophages stimulated with CM from PNF cells, and the inhibition of CCL2 mRNA expression was enhanced to 50% with combination treatment. Taken together, our data suggest that MSU-42011 should be tested in relevant preclinical models of NF1.

In conclusion, MSU42011 increased recruitment and activation of CD4 T cells in vitro and in HER2+ mammary tumors. These data, in combination with our previous work showing that RXR agonists reduce expression of tumor-promoting FOXP3 T cells in vitro and in vivo, confirm a strong correlation between RXR pharmacologic activation and CD4 T cell activation within the tumor microenvironment.

Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.

P1, N=39, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2023 --> Jun 2023

P1, N=24, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Nov 2022 --> Mar 2022

Maculopapular rash at the treatment site was the most common adverse event related to study drug and resolved within a few days of discontinuation. Bexarotene was detectable in breast tissue at the 10mg daily every other day dose.

P1/2, N=84, Recruiting, University of Alabama at Birmingham | Trial completion date: Aug 2022 --> Aug 2024 | Trial primary completion date: Aug 2022 --> Aug 2023

P1, N=38, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2022 --> Jun 2022

P1, N=41, Recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2022 --> Dec 2022 | Trial primary completion date: Feb 2022 --> Dec 2022

P1, N=45, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P1, N=45, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P1, N=27, Active, not recruiting, National Cancer Institute (NCI) | N=40 --> 27

P1, N=45, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jul 2021 --> Feb 2022

P1, N=45, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Apr 2021 --> Jul 2021

6-Me decreased oncogenicity and reduced cancer cell stemness of neuroblastoma PDXs, warranting further exploration of 6-Me as potential novel therapy for neuroblastoma.

P1, N=45, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Feb 2022 --> Apr 2021

Furthermore, we determined that bexarotene-induced apoptotic C6 cells enhanced through Annexin V-FITC/PI staining and caspase-3/-7 activation analyses since phosphatidylserine level on the outer surface of the cell membrane and caspase-3/-7 activities were increased in the cells treated with bexarotene. In conclusion, bexarotene treatment in C6 glioma cells could modulate apoptosis profile, DNA damage, ROS production, and reduction of TAS levels through inhibition of NF-κB by enhancing PPARγ expression.

P1/2, N=84, Recruiting, University of Alabama at Birmingham | Not yet recruiting --> Recruiting

6-Methyl-UAB30 decreased oncogenicity and reduced cancer cell stemness of human neuroblastoma PDXs. These findings warrant further exploration of 6-Me as potential novel therapy for high-risk neuroblastoma.

Our results suggest that the combination of PPARγ and RXR agonists has potential as a chemotherapeutic strategy for thyroid cancer.

The ability to form tumorspheres and mRNA abundance of known stemness markers were also significantly decreased following treatment with UAB30, further indicating decreased cancer cell stemness. These results provide evidence that UAB30 decreased tumorigenicity and cancer cell stemness in neuroblastoma PDXs, warranting further exploration as therapy for high-risk neuroblastoma.

Notably, IRX4204 reduced in vitro human T cell proliferation and enhanced Treg generation in mixed lymphocyte reaction cultures. Collectively, these beneficial effects indicate that targeting RXRs with IRX4204 could be used as a novel approach to prevent acute GVHD in the clinic.

Additionally, peretinoin as a potential drug is in progress of several phase III clinical trials. It's promising that differentiation therapy for HCC may be a part of options in future HCC treatment.