Clinical Trial: Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Subjects With Locally Advanced, Recurrent or Metastatic Adenoid Cystic Carcinoma (ACC)

Brief Summary: 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.

Detailed Summary:

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 lin
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective response according to RECIST 1.1 criteria [ Time Frame: Up to 180 days after the last dose of vorinostat ]

Original Primary Outcome: Objective response as measured by RECIST criteria

Current Secondary Outcome:

• OS [ Time Frame: From the start of treatment until death from any cause, assessed up to 180 days after the last dose of vorinostat ]
  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.
• PFS [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 180 days after the last dose of vorinostat ]
  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.
• 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 after the last dose of vorinostat ]
  Distribution will be estimated using standard survival analysis techniques, and the Kaplan-Meier (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.
• Toxicity as assessed by the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 180 days after the last dose of vorinostat ]
  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.
• TTR [ 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 ]
  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.

Original Secondary Outcome:

• Toxicity
• Time to response
• Response duration
• Progression-free survival
• Overall survival

Dates:
Date Received: August 4, 2010
Date Started: August 2010
Date Completion:
Last Updated: December 26, 2016
Last Verified: December 2016