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

January 9, 2024 updated by: Kyunghee Burkitt, DO, PhD

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 approved therapy for your tumor condition. 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 be in either one of two study groups: Group 1 will receive standard chemoradiation, while group 2 will receive the study drug (Vorinostat) as a pre-treatment, followed by standard chemoradiation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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. This study has two arms to compare cisplatin with radiation therapy for a total of seven weeks versus Vorinostat followed by combination with cisplatin and radiation therapy for a total of seven weeks.

Study Type

Interventional

Enrollment (Estimated)

64

Phase

  • 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 Locations

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

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

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 of low surgical or regional nodes stage (2 or 3, except T1N2).
  • 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 within normal institutional limits
  • 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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard of care chemoradiation
Participant will be treated with standard chemoradiation
Drug: Cisplatin
Cisplatin (100 mg/m2 every 3 weeks)
Radiation: Radiation therapy
Radiation therapy (70 Gy) for total of 7 weeks
Experimental: Study drug + Standard of care chemoradiation
Participant will be pre-treated with study drug followed by continuation of standard chemoradiation
Drug: Cisplatin
Cisplatin (100 mg/m2 every 3 weeks)
Radiation: Radiation therapy
Radiation therapy (70 Gy) for total of 7 weeks
Drug: Vorinostat
Pre-treatment; 300 mg every other day

What is the study measuring?

Primary Outcome Measures

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

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

Kyunghee Burkitt, DO, PhD

Investigators

  • 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)

June 1, 2024

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

November 1, 2022

First Submitted That Met QC Criteria

November 1, 2022

First Posted (Actual)

November 8, 2022

Study Record Updates

Last Update Posted (Actual)

January 11, 2024

Last Update Submitted That Met QC Criteria

January 9, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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