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| Status |
Public on Dec 25, 2020 |
| Title |
A phase 1 study of guadecitabine plus cisplatin in platinum refractory germ cell tumors [Methylation] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Germ cell tumors (GCTs) can be cured with cisplatin-based therapy, although a clinically significant number of patents are refractory and die of progressive disease. Based on preclinical studies indicating that refractory testicular GCTs are hypersensitive to hypomethylating agents (HMA), we conducted a phase I trial [NCT02429466] of the next-generation HMA guadecitabine (SGI-110) in combination with cisplatin in patients with recurrent, cisplatin-resistant GCTs. The primary endpoint was safety and toxicity including DLT and MTD. A total of 14 patients were enrolled. The majority of patients were heavily pretreated. MTD was determined to be 30 mg/m2 guadecitabine followed by cisplatin 100 mg/m2. DLTs were neutropenia and thrombocytopenia. Three patients had partial responses by RECIST criteria, two of these patients qualified as complete responses by serum tumor marker criteria with survival of 16 and 26 months. Three patients also had stable disease for an overall response rate of 23% and clinical benefit rate of 46%. Genome-wide analysis pre- and post-guadecitabine indicated dramatic and widespread global DNA demethylation in cell-free plasma samples including in the promoters of genes of cancer related pathways. In summary, the combination of guadecitabine followed by cisplatin was tolerable and demonstrated biological activity in patients with platinum refractory GCTs.
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| Overall design |
Tumor Biopsy was obtained from patient at baseline C1D1 (pretreatment; prior to first 30 mg/m2 quadecitabine dose) and then on C1D8 (posttreatment; after 5 consecutive doses of guadecitabine and just prior to cisplatin). Bisulphite converted DNA from the 2 samples were hybridised to the Infinium MethylationEPIC beadchip array
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| Contributor(s) |
Fazal Z, Spinella M |
| Citation(s) |
33135391 |
| |
| Submission date |
Jun 18, 2020 |
| Last update date |
Feb 08, 2021 |
| Contact name |
Michael Spinella |
| E-mail(s) |
spinella@illinois.edu
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| Organization name |
University of Illinois at Urbana-Champaign
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| Department |
Comparative Biosciences
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| Street address |
2001 S Lincoln Ave
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| City |
Urbana |
| State/province |
IL |
| ZIP/Postal code |
61801-2325 |
| Country |
USA |
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| Platforms (1) |
| GPL23976 |
Illumina Infinium HumanMethylation850 BeadChip |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA640431 |
