Vorinostat in Combination With Chemoradiation in Locally Advanced HPV Negative HNSCC

NCT05608369 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: CASE2321
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HPV-Related Squamous Cell Carcinoma; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Hypopharynx

Keywords

Squamous Cell Carcinoma; HPV-Related Squamous Cell Carcinoma; Chemoradiation; Locally Advanced HPV negative HNSCC

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  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 Outcomes (1)

• Objective response rate

  Through completion of follow-up (estimated to be 2.5 years)

Study Arms (1)

Study drug + Standard of care chemoradiation

EXPERIMENTAL

Participant will be pre-treated with study drug followed by continuation of standard chemoradiation

Drug: Cisplatin; Radiation: Radiation therapy; Drug: Vorinostat

Interventions

Cisplatin DRUG

Cisplatin100 mg/m2 every 3 weeks or 40 mg/m2 weekly

Study drug + Standard of care chemoradiation

Radiation therapy RADIATION

Radiation therapy (70 Gy) for total of 7 weeks

Study drug + Standard of care chemoradiation

Vorinostat DRUG

Pre-treatment; 300 mg every other day and ends with the dose closest to the last fraction of radiation (total of 8 weeks)

Study drug + Standard of care chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

Cisplatin; Radiotherapy; Vorinostat

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Kyunghee Burkitt, DO, PhD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 8, 2022
• Study Start: June 1, 2025
• Primary Completion: August 1, 2025
• Study Completion: February 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Investigators who provide a methodologically sound proposal for use of requested data

Locations

US (1)