Evaluation of ABEMACICLIB Monotherapy in Patients With Locally Advanced/Metastatic Head and Neck Cancer After Failure of Platinum and Cetuximab or Anti-EGFR-based Therapy and Harboring an Homozygous Deletion of CDKN2A, and/or an Amplification of CCND1 and/or of CDK6

Summary

This trial is an open-label, single arm, Phase II study using an A'Hern single stage design. The molecular prescreening step will allow to defined HPV tumor status as well as molecular status CDKN2A, CCND1 and CDK6. Following this centralized molecular screening, only patients with HPV negative status and with tumor harboring CDKN2A homozygous deletion and/or CCND1 amplification and/or CDK6 amplification could initiate abemaciclib at time of documented radiological progression. Patients will be treated with ABEMACICLIB, 400 mg/day with 2 doses of 200 mg 12 hour apart (QH12). A cycle is defined as an interval of 28 days. For each 28-day cycle, a total of 56 doses of study drug will be dispensed.

Timeline

Start

2018-02-05

Primary completion

2022-11-05

Completion

2022-12-05

Publications

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• Background Molin Y, Fayette J. Current chemotherapies for recurrent/metastatic head and neck cancer. Anticancer Drugs. 2011 Aug;22(7):621-5. doi: 10.1097/CAD.0b013e3283421f7c.
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• Background Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.
• Background Fayette J, Montella A, Chabaud S, Bachelot T, Pommier P, Girodet D, Racadot S, Montbarbon X, Favier B, Zrounba P. Paclitaxel is effective in relapsed head and neck squamous cell carcinoma: a retrospective study of 66 patients at a single institution. Anticancer Drugs. 2010 Jun;21(5):553-8. doi: 10.1097/CAD.0b013e3283388e60.
• Background Sherr CJ. Cancer cell cycles. Science. 1996 Dec 6;274(5293):1672-7. doi: 10.1126/science.274.5293.1672.
• Background Ortega S, Malumbres M, Barbacid M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta. 2002 Mar 14;1602(1):73-87. doi: 10.1016/s0304-419x(02)00037-9.
• Background Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006 Apr 10;24(11):1770-83. doi: 10.1200/JCO.2005.03.7689.
• Background Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999 Jun 15;13(12):1501-12. doi: 10.1101/gad.13.12.1501. No abstract available.
• Background Michalides RJ, van Veelen NM, Kristel PM, Hart AA, Loftus BM, Hilgers FJ, Balm AJ. Overexpression of cyclin D1 indicates a poor prognosis in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 1997 May;123(5):497-502. doi: 10.1001/archotol.1997.01900050045005.
• Background Akervall JA, Michalides RJ, Mineta H, Balm A, Borg A, Dictor MR, Jin Y, Loftus B, Mertens F, Wennerberg JP. Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclin D1 overexpression. Cancer. 1997 Jan 15;79(2):380-9.
• Background Liggett WH Jr, Sewell DA, Rocco J, Ahrendt SA, Koch W, Sidransky D. p16 and p16 beta are potent growth suppressors of head and neck squamous carcinoma cells in vitro. Cancer Res. 1996 Sep 15;56(18):4119-23.
• Background Kothari V, Mulherkar R. Inhibition of cyclin D1 by shRNA is associated with enhanced sensitivity to conventional therapies for head and neck squamous cell carcinoma. Anticancer Res. 2012 Jan;32(1):121-8.
• Background Chung CH, Zhang Q, Kong CS, Harris J, Fertig EJ, Harari PM, Wang D, Redmond KP, Shenouda G, Trotti A, Raben D, Gillison ML, Jordan RC, Le QT. p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. J Clin Oncol. 2014 Dec 10;32(35):3930-8. doi: 10.1200/JCO.2013.54.5228. Epub 2014 Sep 29.

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Indications