This phase II trial studies how well vorinostat works in treating patients with adenoid cystic carcinoma that has come back (recurrent) or that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To evaluate the efficacy by means of response rate (based on Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) of vorinostat in the treatment of patients with locally advanced, recurrent or metastatic adenoid cystic carcinoma (ACC). SECONDARY OBJECTIVES: I. To characterize the safety and tolerability of vorinostat in this patient population. II. To assess the time to tumor response (TTR). III. To assess the response duration (RD). IV. To evaluate progression free survival (PFS). V. To assess overall survival (OS). TERTIARY OBJECTIVES: I. To assess the association between a metabolic response by positron emission tomography (PET)/computed tomography (CT) after one cycle of chemotherapy and subsequent best tumor response according to standard anatomic response evaluation criteria (RECIST). II. To assess the association between a metabolic response by PET/CT after the first and second chemotherapy cycle and PFS. III. To assess flow sort diploid, aneuploid, and tetraploid populations of tumor cells from formalin fixed, paraffin-embedded (FFPE) tissue blocks from patients who benefited from suberoylanilide hydroxamic acid (SAHA) therapy and from patients who did not demonstrate a durable benefit. IV. Profile the genomes of each cell population using oligonucleotide comparative genomic hybridization (CGH) arrays. V. Perform whole exome analysis of the sorted tumor population and matching germ line sample for each of the patients selected. VI. To assess stable disease duration (SDD). VII. To assess the association between response to vorinostat treatment and RAD23 homolog B (HR23B) on tumor paraffin blocks. VIII. Retrospectively compare volumetric density (viable tumor volume = VTV) with pre-determined RECIST of target lesions in cross sectioning imaging (CT/magnetic resonance \[MR\]) already obtained. IX. Correlate VTV, RECIST and treatment response (partial response, stable disease, progressive disease and stable disease over 6 months). OUTLINE: Patients receive vorinostat orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up for 180 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Correlative studies
Given PO
City of Hope Comprehensive Cancer Center
Duarte, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
Yale University
New Haven, Connecticut, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Case Western Reserve University
Cleveland, Ohio, United States
Cleveland Veterans Administration
Cleveland, Ohio, United States
Lake University Ireland Cancer Center
Mentor, Ohio, United States
...and 2 more locations
Objective Response According to RECIST 1.1 Criteria
Objective (Best) response according to RECIST 1.1 criteria.
Time frame: Up to 180 days after the last dose of vorinostat maximum treatment duration= 24 months
Number of Participants With Grade 3 or Grade 4 Toxicity as Assessed by the Common Terminology Criteria for Adverse Events Version 4.0
Toxicity will be tabulated via frequency distributions, and also dichotomized to report the proportion (and percentage) of patients experiencing a specified level (e.g., grade 3-4) of toxicity.
Time frame: Up to 180 days after the last dose of vorinostat maximum treatment duration= 24 months
Time to Recurrence (TTR)
TTR will be summarized descriptively, reporting N, median, mean, standard deviation, standard error (SE), minimum, maximum, and 90% CI for the mean calculated from the SE and asymptotic normal distribution theory.
Time frame: From the start of the treatment until the RECIST measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded, assessed up to 180 days after the last dose of vorinostat maximum treatment duration= 24 months
Response Duration (RD)
Median point estimate and full range will be documented, since only two patients achieved a response.
Time frame: From the time measurement criteria are met for CR or PR (whichever is first) until the first date that recurrence or progression is objectively documented, assessed up to 60 months after the last dose of vorinostat max. treatment duration= 24 months
Progression-free Survival (PFS)
Distribution will be estimated using standard survival analysis techniques, and the K-M method. From the K-M life tables, both median point estimate and 90% confidence interval (CI) estimate.
Time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 60 months after the last dose of vorinostat maximum treatment duration= 24 months
Overall Survival (OS)
Distribution will be estimated using standard survival analysis techniques, and the K-M method. From the K-M life tables, both point and 90% CI estimates of various statistics of interest can be calculated (e.g., median, 6-month event-free rate, 12-month event-free rate, etc.). Statistical graphs of each K-M curve (with 90% CI lines) will be generated for visual display. (One year survival rate will be given since OS median was not reached due to too few events)
Time frame: From the start of treatment until death from any cause, duration for reported probability= 1 year; survival data collected for up to a total of 60 months
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