Vorinostat in Combination With Chemoradiation in Locally Advanced HPV Negative HNSCC

Sponsor

Kyunghee Burkitt, DO, PhD (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05608369

Collaborator

(none)

Enrollment

Location

Arms

9.1

Anticipated Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Cisplatin Radiation: Radiation therapy Drug: Vorinostat	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression free survival [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).

Secondary Outcome Measures

Objective response rate [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.