Vorinostat + Azacitidine for Head and Neck Cancers

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Sodium valproate, others

Disqualifiers: CNS involvement, Uncontrolled illness, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of two drugs, vorinostat (a histone deacetylase inhibitor) and azacitidine (a chemotherapy), to determine the optimal dose and understand their side effects in treating certain head and neck cancers. The focus is on cancers that have recurred or spread, specifically nasopharyngeal cancer and a type of lymphoma affecting nasal passages. These drugs aim to stop cancer cells from growing and spreading by blocking certain enzymes. Suitable participants have a type of nasopharyngeal cancer or nasal lymphoma that has returned or spread and cannot be treated with surgery or additional radiation. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy or radiotherapy within 4 weeks before starting the trial. Also, you should not have taken sodium valproate for at least 2 weeks prior to enrollment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of vorinostat and azacitidine is generally safe and tolerable. In one study involving 41 patients with various types of leukemia, vorinostat did not cause serious side effects for most participants. Another study explored the use of vorinostat with azacitidine in patients with more severe blood disorders, showing positive results and suggesting effectiveness with minimal issues.

Although these drugs remain under investigation, early findings indicate safety for many individuals. Since this trial is in an early phase, it primarily focuses on assessing the treatment's safety and determining the appropriate dose. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Vorinostat and Azacitidine for head and neck cancers because these drugs work in a unique way compared to traditional treatments. Most treatments for these cancers, like surgery, radiation, and chemotherapy, focus on removing or destroying cancer cells directly. However, Vorinostat and Azacitidine are epigenetic drugs that alter the way cancer cells read their DNA, potentially reactivating genes that suppress tumors. This novel approach could offer new hope, especially for patients who have not responded well to conventional therapies.

What evidence suggests that vorinostat and azacitidine might be an effective treatment for head and neck cancers?

Research has shown that combining vorinostat and azacitidine can help treat certain cancers. In earlier studies, this combination improved blood conditions in 7 patients, with 2 experiencing complete responses, meaning their cancer was no longer active. In this trial, participants will receive both vorinostat and azacitidine. Vorinostat blocks enzymes that cancer needs to grow, while azacitidine stops cancer cells from dividing or spreading. Together, they may more effectively kill cancer cells. These early results are promising, but more research is needed to confirm their effectiveness for head and neck cancers specifically. ^{1 2 3 6 7}

Who Is on the Research Team?

Wen-Son Hsieh

Principal Investigator

Johns Hopkins Singapore

Are You a Good Fit for This Trial?

This trial is for adults with nasopharyngeal cancer or nasal natural killer T-cell lymphoma that has returned or spread, who have already tried at least one chemotherapy treatment. They must be in good enough health to participate, not pregnant, willing to use contraception, and not have any serious illnesses that could interfere with the study.

Inclusion Criteria

My cancer has come back in the same area but cannot be treated with radiation to cure it.

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

I have cancer that has spread or returned and was treated with chemotherapy after it came back.

Exclusion Criteria

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

Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with 5AC and SAHA

I do not have chronic active hepatitis B.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive azacitidine subcutaneously on days 1-10 and vorinostat orally twice daily on days 1-14. Treatment repeats every 28 days for 4 courses.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Patients with responding disease may continue treatment at the discretion of the principal investigator.

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Vorinostat

Trial Overview The trial is testing the combination of two chemotherapy drugs, Vorinostat and Azacitidine. It aims to find the safest doses and see how well they work together against recurrent or metastatic nasopharyngeal cancer or nasal NK T-cell lymphoma by blocking enzymes needed for cell growth.

How Is the Trial Designed?

Group I: Treatment (azacitidine, vorinostat) Experimental Treatment 4 Interventions

Patients receive azacitidine SC on days 1-10 and vorinostat PO BID on days 1-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Vorinostat, a histone deacetylase inhibitor, did not cause maternal toxicity or major fetal malformations in Sprague-Dawley rats and Dutch Belted rabbits, indicating a relatively safe profile during pregnancy at lower doses.

However, at high doses, vorinostat was associated with developmental toxicity, such as decreased fetal weight and skeletal variations, suggesting that while it is generally safe, caution is needed with higher dosages due to potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of developmental toxicity of vorinostat, a histone deacetylase inhibitor, in Sprague-Dawley rats and Dutch Belted rabbits. Wise, LD., Turner, KJ., Kerr, JS.[2018]

In a phase I study involving 23 advanced-stage cancer patients, vorinostat was found to be safe and tolerable, with common side effects including mild to moderate nausea and fatigue.

The study revealed that a high-fat meal slightly increased the absorption of vorinostat but did not significantly impact its overall effectiveness, suggesting that vorinostat can be administered with or without food in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study to determine the effects of food and multiple dosing on the pharmacokinetics of vorinostat given orally to patients with advanced cancer. Rubin, EH., Agrawal, NG., Friedman, EJ., et al.[2018]

In a phase I/II trial involving 33 patients with EGFR-mutated non-small cell lung cancer (NSCLC) who progressed after tyrosine kinase inhibitors, the combination of vorinostat and erlotinib was found to be safe, with a maximum tolerated dose established for the treatment regimen.

Despite the safety of the drug combination, the study reported no significant therapeutic responses, with a progression-free survival rate of only 28% at 12 weeks, indicating that this treatment may not be effective for patients who have already progressed on other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression. Reguart, N., Rosell, R., Cardenal, F., et al.[2022]

Vorinostat, a histone deacetylase inhibitor, was found to be safe and tolerable in a phase 1 study involving 41 patients with various types of leukemia and myelodysplastic syndromes, with a maximum tolerated dose of 200 mg twice daily or 250 mg thrice daily.

The treatment led to hematologic improvements in 7 patients, including 2 complete responses, and increased histone acetylation was observed, suggesting its potential efficacy in treating acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. Garcia-Manero, G., Yang, H., Bueso-Ramos, C., et al.[2021]

Vorinostat (SAHA) shows varying effectiveness in treating breast cancer, with some tumors and cell lines being resistant due to differences in gene expression related to cell adhesion and glutathione metabolism.

Depleting glutathione with buthionine sulfoximine (BSO) can enhance the effectiveness of SAHA, suggesting that evaluating antioxidant gene expression may help predict which tumors will respond to this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redox-Mediated Suberoylanilide Hydroxamic Acid Sensitivity in Breast Cancer. Chiaradonna, F., Barozzi, I., Miccolo, C., et al.[2018]

Vorinostat, when used sequentially before cytosine arabinoside (ara-C), showed mostly synergistic effects in killing leukemia cells, suggesting a promising treatment strategy for acute leukemias.

The combination of vorinostat with etoposide was found to be additive to synergistic, especially when etoposide was administered after vorinostat, indicating that the timing of drug administration is crucial for maximizing therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical studies of vorinostat (suberoylanilide hydroxamic acid) combined with cytosine arabinoside and etoposide for treatment of acute leukemias. Shiozawa, K., Nakanishi, T., Tan, M., et al.[2018]

Citations

1. withpower.com withpower.com/trial/phase-1-carcinoma-squamous-cell-2-2006-b0e39

Vorinostat + Azacitidine for Head and Neck Cancers The treatment led to hematologic improvements in 7 patients, including 2 complete responses, and increased histone acetylation was observed, suggesting its ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17960324/

Phase II trial of the histone deacetylase inhibitor vorinostat ... This phase II trial was initiated to assess the efficacy and safety of oral vorinostat (Zolinza, suberoylanilide hydroxamic acid, SAHA) in patients with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2731787/

Vorinostat in solid and hematologic malignancies - PMC This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01748240

Addition of Vorinostat to Azacitidine in Higher Risk MDS a ... Patient treated upfront with a combination of this agents have shown more responses based on phase I/II data. In the present study, we will use the combination ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024090832;

Stochasticity of anticancer mechanisms underlying clinical ... Vorinostat, or suberoyl-anilide hydroxamic acid (SAHA) (Fig. 1), has been shown to be effective in treating specific cancer forms [12]. In ...

6. med.stanford.edu med.stanford.edu/content/sm/ohns/research/clinical-trials-dynamic/clinical-trial-detail.html?start=3940

Clinical Trial Detail | Otolaryngology - Stanford Medicine Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether azacitidine is more effective ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/26/4/837/83019/A-Phase-II-Trial-of-Pembrolizumab-and-Vorinostat

A Phase II Trial of Pembrolizumab and Vorinostat in Recurrent ... This clinical trial combined pembrolizumab and vorinostat in recurrent/metastatic squamous cell carcinomas of the head and neck (HN), and salivary gland cancer ...