Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma
This phase II trial is studying how well vorinostat works in treating patients with locally advanced, recurrent, or metastatic adenoid cystic carcinoma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
Recurrent Salivary Gland Cancer
Salivary Gland Adenoid Cystic Carcinoma
Stage III Adenoid Cystic Carcinoma of the Oral Cavity
Stage III Salivary Gland Cancer
Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
Stage IV Salivary Gland Cancer
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Subjects With Locally Advanced, Recurrent or Metastatic Adenoid Cystic Carcinoma (ACC) (IND 71976)|
- Objective response according to RECIST 1.1 criteria [ Time Frame: Up to 180 days ] [ Designated as safety issue: No ]
- Toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 180 days ] [ Designated as safety issue: Yes ]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. Analysis of these proportions (i.e., rates) will include both point and 90% confidence interval (CI) estimates, with the CI estimates calculated via Wilson's method.
- Time to response (TTR) [ Time Frame: From the start of the treatment until the RECIST measurement criteria are met for CR or PR (whichever is first recorded, assessed up to 180 days ] [ Designated as safety issue: No ]TTR will be summarized descriptively, reporting N, median, mean, standard deviation (SD), standard error (SE), minimum, maximum, and 90% CI for the mean calculated from the SE and asymptotic Normal distribution theory.
- Response duration (RD) [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 180 days ] [ Designated as safety issue: No ]
- Progression free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 180 days ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: From the start of treatment until death from any cause, assessed up to 180 days ] [ Designated as safety issue: No ]Distribution will be estimated using standard survival analysis techniques, and the Kaplan-Meier (K-M) method.
|Study Start Date:||August 2010|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vorinostat)
Patients receive vorinostat PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: laboratory biomarker analysis
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).
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).
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. To profile the genomes of each cell population using oligonucleotide comparative genomic hybridization (CGH) arrays. This will confirm the identification of tumor populations in each sample and provide genomic landmarks for next generation sequencing (NGS) analysis.
V. To 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 HR23B on tumor paraffin blocks.
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 6 months.
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|City of Hope Medical Group Inc|
|Pasadena, California, United States, 91105|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Ohio|
|Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|Cleveland Veterans Administration|
|Cleveland, Ohio, United States, 44106|
|Lake University Ireland Cancer Center|
|Mentor, Ohio, United States, 44060|
|Ireland Cancer Center at Firelands Regional Medical Center|
|Sandusky, Ohio, United States, 44870|
|Ontario Cancer Institute at Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Patricia LoRusso||Barbara Ann Karmanos Cancer Institute|