Vorinostat in Combination With Chemoradiation in Locally Advanced HPV Negative HNSCC (HPV)

April 2, 2025 updated by: Case Comprehensive Cancer Center

A Phase 2 Study of Vorinostat in Combination With Chemoradiation in Patients With Locally Advanced HPV Negative HNSCC

The purpose of this study is to learn more about a drug called Vorinostat (an experimental drug) in combination with chemoradiation. The intention of this study is to learn if this drug is safe for the participants and whether this drug with chemoradiation is able to further increase the clinical efficacy of chemoradiation, which is an approved therapy. The main question it aims to answer is: How may Vorinostat interact with standard chemotherapy and radiation therapy in head and neck cancer? Participants will receive the study drug (Vorinostat) as a pre-treatment, followed by standard chemoradiation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Histone deacetylase (HDAC) inhibitors have been shown to increase reverse resistance to cisplatin and radiation therapy. This phase 2 study comes after an already completed phase 1 study which examined tolerability of pan-HDAC inhibitor, Vorinostat, in combination with chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC). The study showed that Vorinostat in combination with concurrent chemoradiation therapy (CRT) is safe and estimated 5-year OS of HPV- patients is 77.8% which is considerably higher than the 5-year overall survival (OS) of 46.2% in HPV- HNSCC patients treated with standard concurrent chemoradiation. Based on this phase 1 study, the hypothesis is that Vorinostat, in combination with chemoradiation, will increase median progression-free survival compared to chemoradiation alone treatment in HPV-HNSCC.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subjects must have histologically or cytologically confirmed stage III or IV HPV negative squamous cell carcinoma of the oral cavity, oropharynx or hypopharynx, tumors is deemed to be either unresectable or locally advanced.
  • Subjects must have received no prior therapies (chemotherapy or radiotherapy) for this disease
  • Age >18 years. Because the low occurrence of HNSCC in the pediatric population, children are excluded from this study
  • ECOG Performance status ≤ 2

  • Subjects must have normal organ and marrow function as defined below

    • Hemoglobin ≥ 9.0 g/dl (transfusion permitted)
    • Leukocytes ≥ 3,000/mcL
    • Absolute neutrophil count ≥ 1,500/mcL
    • Platelet count ≥ 100,000/mcL
    • Total bilirubin within normal institutional limits
    • AST (SGOT) ≤ 2.5 X institutional upper limit of normal
    • ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
    • Serum Creatinine clearance (> 50 ml/min)
  • Based on findings from animal studies and its mechanism of action, vorinostat can cause fetal harm when administered to a pregnant woman. There are insufficient data on vorinostat use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, vorinostat crossed the placenta and caused adverse developmental outcomes at exposures approximately 0.5 times the human exposure based on AUC0-24 hours. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) beginning at study entry and for the duration of study participation. Male study participants should use an additional barrier method of contraception for 30 days following the last dose of vorinostat. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Patients must have measurable disease, per RECIST 1.1
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Eligibility for curative-intent surgery, previous chemotherapy.
  • Subjects receiving any other investigational agents.
  • Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat.
  • Patients with previous exposure to vorinostat.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because vorinostat may have potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated with vorinostat. These potential risks may also apply to other agents used in this study.
  • HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with vorinostat. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated. Also include whether HIV testing is required for this study, or only if a known diagnosis will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Study drug + Standard of care chemoradiation
Participant will be pre-treated with study drug followed by continuation of standard chemoradiation
Radiation: Radiation therapy
Radiation therapy (70 Gy) for total of 7 weeks
Drug: Cisplatin
Cisplatin100 mg/m2 every 3 weeks or 40 mg/m2 weekly
Drug: Vorinostat
Pre-treatment; 300 mg every other day and ends with the dose closest to the last fraction of radiation (total of 8 weeks)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: Through completion of follow-up (estimated to be 2.5 years)
Determine progression free survival (PFS) of patient with locally advanced HPV- HNSCC treated with vorinostat and standard chemoradiation (CRT).
Through completion of follow-up (estimated to be 2.5 years)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: Through completion of follow-up (estimated to be 2.5 years)
Determine objective response rate (ORR), overall survival (OS) of patient with locally advanced HPV- HNSCC treated with vorinostat and standard chemoradiation (CRT).
Through completion of follow-up (estimated to be 2.5 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Case Comprehensive Cancer Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kyunghee Burkitt, DO, PhD, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 1, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 8, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 4, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CASE2321

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie or influence the results observed in this study

IPD Sharing Time Frame

Beginning 3 months and ending 5 years following article publication

IPD Sharing Access Criteria

Investigators who provide a methodologically sound proposal for use of requested data

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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