Vorinostat in Combination With Chemoradiation in Locally Advanced HPV Negative HNSCC

NCT ID: NCT05608369

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2026-02-01

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.

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study drug + Standard of care chemoradiation

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

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

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

Radiation therapy

Intervention Type: RADIATION

Radiation therapy (70 Gy) for total of 7 weeks

Vorinostat

Intervention Type: DRUG

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

Interventions

Cisplatin

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

Intervention Type: DRUG

Radiation therapy

Radiation therapy (70 Gy) for total of 7 weeks

Intervention Type: RADIATION

Vorinostat

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kyunghee Burkitt, DO, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Locations

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CASE2321

Identifier Type: -

Identifier Source: org_study_id