Clinical Trials Search at Vanderbilt-Ingram Cancer Center
Evexomostat Plus Alpelisib and Fulvestrant in Women With the PIK3CA Mutation With HR+/Her2- Breast Cancer
The PIK3CA gene is frequently mutated in breast cancer, leading to disease aggressiveness and
patient mortality. Alpelisib, a small molecule that inhibits the activity of the PIK3CA gene
product PI3K, has demonstrated clinical benefit in cancer patients with this gene mutation.
However, hyperglycemia, an on-target toxicity associated with alpelisib that leads to
hyperinsulinemia, limits the drug's clinical efficacy and induces high grade hyperglycemia in
patients with baseline metabolic dysfunction, insulin resistance and/or elevated HbA1c.
Restoring insulin sensitivity and reduction in circulating concentrations of insulin have
been reported to improve the activity of alpelisib.
Evexomostat (SDX-7320) is a polymer-conjugate of a novel small molecule methionine
aminopeptidase 2 (MetAP2) inhibitor that has demonstrated the ability to reduce
alpelisib-induced hyperglycemia in multiple animal experiments and has demonstrated
synergistic anti-tumor activity independent of changes in glucose or insulin. Evexomostat was
well tolerated in a Phase 1 safety study in late-stage cancer patients and showed
improvements in insulin resistance for patients that presented with baseline elevated
insulin. Overall, the most common treatment-emergent adverse events with evexomostat (TEAEs)
were fatigue (44%), decreased appetite (38%), constipation and nausea (each 28%), and
diarrhea (22%). All other TEAEs occurred at an incidence <20%.
The purpose of this study is to characterize the safety of the triplet drug combination
(alpelisib, fulvestrant plus evexomostat), to test whether evexomostat, when given in
combination with alpelisib and fulvestrant will reduce the number and severity of
hyperglycemic events and/or reduce the number of anti-diabetic medications needed to control
the hyperglycemia for patients deemed at risk for alpelisib-induced hyperglycemia (baseline
elevated HbA1c or well-controlled type 2 diabetes), and to assess preliminary anti-tumor
efficacy and changes in key biomarkers and quality of life in this patient population.
patient mortality. Alpelisib, a small molecule that inhibits the activity of the PIK3CA gene
product PI3K, has demonstrated clinical benefit in cancer patients with this gene mutation.
However, hyperglycemia, an on-target toxicity associated with alpelisib that leads to
hyperinsulinemia, limits the drug's clinical efficacy and induces high grade hyperglycemia in
patients with baseline metabolic dysfunction, insulin resistance and/or elevated HbA1c.
Restoring insulin sensitivity and reduction in circulating concentrations of insulin have
been reported to improve the activity of alpelisib.
Evexomostat (SDX-7320) is a polymer-conjugate of a novel small molecule methionine
aminopeptidase 2 (MetAP2) inhibitor that has demonstrated the ability to reduce
alpelisib-induced hyperglycemia in multiple animal experiments and has demonstrated
synergistic anti-tumor activity independent of changes in glucose or insulin. Evexomostat was
well tolerated in a Phase 1 safety study in late-stage cancer patients and showed
improvements in insulin resistance for patients that presented with baseline elevated
insulin. Overall, the most common treatment-emergent adverse events with evexomostat (TEAEs)
were fatigue (44%), decreased appetite (38%), constipation and nausea (each 28%), and
diarrhea (22%). All other TEAEs occurred at an incidence <20%.
The purpose of this study is to characterize the safety of the triplet drug combination
(alpelisib, fulvestrant plus evexomostat), to test whether evexomostat, when given in
combination with alpelisib and fulvestrant will reduce the number and severity of
hyperglycemic events and/or reduce the number of anti-diabetic medications needed to control
the hyperglycemia for patients deemed at risk for alpelisib-induced hyperglycemia (baseline
elevated HbA1c or well-controlled type 2 diabetes), and to assess preliminary anti-tumor
efficacy and changes in key biomarkers and quality of life in this patient population.
Not Available
I/II
Rexer, Brent
NCT05455619
VICCBREP2271
Itacitinib for the Treatment Steroid Refractory Immune Related Adverse Events Arising from Immune Checkpoint Inhibitors
Miscellaneous
Miscellaneous
This phase II trial tests how well itacitinib works in in patients with immune related adverse events (irAEs) arising from immune checkpoint inhibitors (ICI) that do not respond to steroids (steroid refractory). Steroids are the usual treatment for these side effects. However, sometimes steroids do not improve or fix the side effects. Giving itacitinib may be effective in treating patients with known or suspected problems coming from ICIs, that do not resolve or improve with steroids, by reducing the patient's immune system response that can cause the irAEs.
Miscellaneous
II
Johnson, Douglas
NCT05660421
VICCCTT2193
Rigosertib Plus Pembrolizumab in Treating Patients with Unresectable/Metastatic Melanoma Refractory to PD-1 Inhibitors
Melanoma
Melanoma
This phase II clinical trial tests how well rigosertib plus pembrolizumab workings in treating patients with melanoma which cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic), and that has not responded to previous treatment with PD-1 or PD-L1 inhibitors (refractory). Rigosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may change the immune system to make immunotherapy more effective. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving rigosertib in combination with pembrolizumab may be more effective in treating patients with unresectable metastatic melanoma that has not responded to previous treatment with PD-1 or PD-L1 inhibitors than giving either drug alone.
Melanoma
II
Johnson, Douglas
NCT05764395
VICCMEL2218
An Open Label, Expanded Access Protocol using 131I-Metaiodobenzylguanidine (131I-MIBG) Therapy in Patients with Refractory Neuroblastoma, Pheochromocytoma, or Paraganglioma
Multiple Cancer Types
Neuroblastoma (Pediatrics),
Pediatric Solid Tumors
N/A
Kitko, Carrie
NCT01590680
VICCPED1249
Neuroblastoma Maintenance Therapy Trial
Multiple Cancer Types
Difluoromethylornithine (DFMO) will be used in an open label, single agent, multicenter,
study for patients with neuroblastoma in remission. In this study subjects will receive 730
Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 250 mg/m2 BID (strata 1,
2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. This study will focus on
the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to
prevent recurrence.
study for patients with neuroblastoma in remission. In this study subjects will receive 730
Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 250 mg/m2 BID (strata 1,
2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. This study will focus on
the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to
prevent recurrence.
Endocrine,
Neuroblastoma (Pediatrics),
Neuroendocrine,
Pediatrics
II
Pastakia, Devang
NCT02679144
VICCPED16157
A Randomized, Open-Label Pilot Trial to Evaluate the Safety and Efficacy of Carmustine Wafer in Combination with Retifanlimab and Standard Radiation With or Without Temozolomide in Newly-Diagnosed Adult Subjects with Glioblastoma
Multiple Cancer Types
Neuro-Oncology,
Phase I
I
Thompson, Reid
NCT05083754
VICCNEUP22119
Expanded Access to Trametinib for a child with Plexiform Neurofibroma in NF1
Pediatrics
Pediatrics
Pediatrics
N/A
Esbenshade, Adam
VICCPED2251
