A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC).

Abstract

6045 Background: SAHA is a small molecule inhibitor of histone deacetylases (HDAC). Based on confirmed responses noted in 2 ACC patients treated with SAHA at our institution; we initiated this phase II trial. Methods: Patients with LA, recurrent or metastatic ACC and adequate organ function were eligible. Any prior number of chemotherapy regimens was allowed. Tumor tissue and blood were collected for correlative studies. SAHA was administered orally 400 mg daily for 28 days. The primary objective was to evaluate response rate (RR). Secondary endpoints included: time to tumor response (TTR); response duration (RD); progression-free survival (PFS); overall survival (OS); and adverse events (AE). 29 evaluable patients were needed in a Simon 2-stage optimal design to distinguish RR of at most 5% vs. at least 20%, with alpha = 0.15 and power = 0.90. Results: 30 evaluable patients (overenrolled by 1) were accrued from at 5 different centers between August 2010 and June 2012. Median follow up among the censored patients is 3.8 months for PFS, and 7.2 months for OS. 19 patients were female, 24 were Caucasian, median age was 53 years (range 21-73); 21 patients had a performance status of 1; 20 patients were chemo-naïve. The median number of cycles completed was 5 (range 1-27+). Lymphopenia (n=5), hypertension (n=3), oral pain (n=2), thromboembolic events (n=2) and fatigue (n=2) were the only grade 3 AEs that occurred in more than 1 patient. 5 patients were dose reduced due to AEs. At the time of data cut-off, 9/30/2012, 1 patient with lung metastasis had a PR, with RD of 11.2+ months. TTR was 7.7 months. SD was the best response in 25 patients. Median PFS is 12.7 months (90% confidence interval lower limit: 3.7 months). Median OS has not been reached. There were 6 patients with PFS > 1 year. The correlative studies results will be presented. Conclusions: SAHA shows promise in the treatment of ACC. We are awaiting genomic analysis of the tumors to study the basis of clinical benefit (PR and SD) of SAHA in ACC. Future drug combination studies in ACC are being considered focusing on the epigenetic mechanism of SAHA. Supported by 5U01CA062487/19. Clinical trial information: NCT01175980.