Vorinostat + Chemoradiation for Head and Neck Cancer

(HPV Trial)

Overseen By Kyunghee Burkitt, DO, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Investigational agents, Antiretrovirals

Disqualifiers: Pregnancy, Brain metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how a new drug, Vorinostat, works with standard chemoradiation treatment for head and neck cancer. Researchers aim to determine if adding Vorinostat enhances the effectiveness of the usual treatment and if it is safe to use together. They seek participants with advanced squamous cell carcinoma in specific areas of the head and neck who have not undergone chemotherapy or radiation. Individuals with this type of cancer, especially if it is difficult to remove or treat, might be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on HIV medication, you cannot participate due to potential interactions with the trial drug, Vorinostat.

Is there any evidence suggesting that Vorinostat in combination with chemoradiation is likely to be safe for humans?

Research has shown that Vorinostat is already FDA-approved for treating cutaneous T-cell lymphoma, indicating it has undergone safety testing in humans. In one study, 25 patients took Vorinostat, and 11 experienced positive results, including one with head and neck cancer. This suggests the treatment was somewhat effective and tolerated by patients.

Another study examined Vorinostat for head and neck cancer and found it can inhibit cancer cell growth by stopping their division. This finding is promising for its use alongside chemotherapy and radiation.

While these studies provide useful information, every treatment can have side effects. The ongoing clinical trial aims to understand how Vorinostat works with standard treatments like chemotherapy and radiation and to ensure its safety for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Vorinostat combined with standard chemoradiation for head and neck cancer because Vorinostat introduces a novel mechanism of action. Unlike typical treatments that rely solely on chemotherapy and radiation, Vorinostat is a histone deacetylase inhibitor, which can potentially enhance the effectiveness of these traditional therapies. By modifying the expression of certain genes, Vorinostat may make cancer cells more sensitive to the damage caused by chemoradiation, possibly leading to better patient outcomes. This innovative approach could offer a new avenue for tackling head and neck cancer, sparking hope for improved treatment efficacy.

What evidence suggests that Vorinostat with chemoradiation could be effective for head and neck cancer?

Research has shown that Vorinostat, a medication, might help treat head and neck cancer by activating certain genes that can stop tumors. This could potentially prevent cancer cells from growing by blocking the enzymes they need. Studies suggest that targeting these enzymes, known as histone deacetylases (HDACs), could effectively treat head and neck squamous cell carcinoma (HNSCC). In this trial, participants will receive Vorinostat combined with standard chemoradiation. Early results indicate that this combination might enhance the effectiveness of treatment compared to chemoradiation alone. ^{2 6 7 8 9}

Who Is on the Research Team?

Kyunghee Burkitt, DO, PhD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with stage III or IV HPV negative squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx that can't be surgically removed. They must have no prior treatments for this cancer, an ECOG Performance status ≤ 2 (which means they are able to walk and do light activities), normal organ function, and agree to use contraception. Excluded are those with other serious illnesses, previous chemotherapy or vorinostat exposure, untreated brain metastases/CNS disease, HIV on antiretroviral therapy due to interaction risks.

Inclusion Criteria

- Total bilirubin within normal institutional limits.

- AST (SGOT) ≤ 2.5 X institutional upper limit of normal.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

Subjects receiving any other investigational agents.

I do not have any serious illnesses that would stop me from following the study's requirements.

I am eligible for surgery aimed at curing my condition and have had chemotherapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive the study drug Vorinostat as a pre-treatment

2 weeks

Chemoradiation

Participants receive standard chemoradiation therapy in combination with Vorinostat

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Radiation therapy
• Vorinostat

Trial Overview The trial is testing Vorinostat in combination with standard chemoradiation treatment for head and neck cancer. Participants will either receive just the standard treatment (Group 1) or Vorinostat followed by the standard treatment (Group 2). The goal is to see if adding Vorinostat improves outcomes compared to only chemoradiation.

How Is the Trial Designed?

Group I: Study drug + Standard of care chemoradiation Experimental Treatment 3 Interventions

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

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Kyunghee Burkitt, DO, PhD

Lead Sponsor

Trials

1

Recruited

20+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27086484/

Suberoylanilide hydroxamic acid inhibits growth of head ... Conclusion: Our data indicate that SAHA treatment results in reactivation of the silenced tumor suppressor miRs. Furthermore, this study emphasizes the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4979983/

Suberoylanilide hydroxamic acid inhibits growth of head and ... Our data indicate that SAHA treatment results in reactivation of the silenced tumor suppressor miRs. Furthermore, this study emphasizes the usefulness of this ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00045006

Suberoylanilide Hydroxamic Acid in Treating Patients With ... RATIONALE: Suberoylanilide hydroxamic acid may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

4. genesandcancer.com genesandcancer.com/article/54/text/

Suberoylanilide hydroxamic acid (SAHA) reverses ... Taken together, our results suggest that targeting HDACs with SAHA could be an effective treatment strategy for the treatment of HNSCC patients. INTRODUCTION.

5. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05169-9

Targeting histone deacetylases in head and neck ... This review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11159849/

Potential efficacy of the oral histone deacetylase inhibitor ... In preclinical studies, vorinostat exposure resulted in cell cycle arrest and antiproliferative and antitumor activities in lymphoma models.( , , ) In October ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01175980?term=AREA%5BConditionSearch%5D(%22Tongue%20Cancer%22)%20AND%20AREA%5BBasicSearch%5D(gene%20therapy)&rank=9

Vorinostat in Treating Patients With Locally Advanced, ... This phase II trial studies how well vorinostat works in treating patients with adenoid cystic carcinoma that has come back (recurrent) or that has spread ...

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2008.26.15_suppl.15656

A phase I study of vorinostat (suberoylanilide hydroxamic ... Background: Vorinostat is an inhibitor of histone deacetylases with clinical activity in patients (pts) with various types of cancer including cutaneous T-cell ...

9. aacrjournals.org aacrjournals.org/clincancerres/article/13/12/3605/13129/Phase-I-and-Pharmacokinetic-Study-of-Vorinostat-A

Phase I and Pharmacokinetic Study of Vorinostat, A Histone ... Of 25 patients evaluable for response, partial responses occurred in 11 (10 non–small cell lung cancer and 1 head and neck cancer) and stable disease occurred ...