4 Clinical Trials for Various Conditions
This multicenter, open-label, randomized phase 3 trial will determine if palbociclib and cetuximab (Arm 1) improves overall survival (OS) in comparison to cetuximab monotherapy (Arm 2) in patients with CDKN2A-altered, HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who experienced disease progression on a PD-1/L1 inhibitor (given as monotherapy or in combination with other therapy).
The purpose of this study is to evaluate the results of treating patients with HPV-unrelated head and neck squamous cell carcinoma with neoadjuvant single-agent palbociclib, followed by chemoradiation (either cisplatin + IMRT or cetuximab + IMRT depending on patient characteristics), followed by adjuvant single-agent palbociclib.
NRF2 activation, observed in up to 40% of head and neck squamous cell carcinoma (HNSCC) tumors, plays a critical role in tumor progression, metastasis, and radiation therapy resistance. The investigators have recently discovered that pyrimethamine (PYR) and its analogs have an inhibitory effect on NRF2 activity in vitro and in mouse models via inhibition of dihydrofolate reductase (DHFR). Pyrimethamine is an established drug that has been used for decades for treatment of protozoan infections and malaria. A growing body of research shows that it has potential antitumor activity, however its activity on growing human tumors has not been previously studied. The primary efficacy goal of this study is to evaluate the activity of pyrimethamine on human tumors as demonstrated by inhibition of DHFR and downregulation of NRF2 pathway activity. On-target inhibition of DHFR by pyrimethamine results in the stabilization and increased protein expression of human DHFR. The primary efficacy hypothesis of this study is that treatment with pyrimethamine will result in a 50% increase in DHFR protein within the tumor cells as measured by quantitative western blot analysis. Secondarily, among those tumors classified as NRF2-active on pre-treatment biopsy, the investigators hypothesize there will be a 50% reduction in NRF2 activity as measured by SureQuant targeted proteomic analysis.
To determine the outcomes of patients with specific head and neck cancer after undergoing radiation therapy with atezolizumab followed by surgery then radiation with or without chemotherapy according to national guidelines.