~7 spots leftby Sep 2025

5-Azacytidine + Nivolumab for Squamous Cell Carcinoma

Recruiting in Palo Alto (17 mi)
Barbara Burtness, MD < Yale School of ...
Overseen byBarbara Burtness, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Barbara Burtness
Must not be taking: Anticoagulants, Corticosteroids
Disqualifiers: Invasive malignancy, Autoimmune disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study is being done because both 5-azacytidine and nivolumab can influence the immune system's response to HPV-associated head and neck cancer, and we wish to evaluate whether taking 5-azacytidine will make HPV-associated head and neck cancer more sensitive to treatment with nivolumab. 5-Azacytidine (5-AZA) is a chemotherapy, and nivolumab is an immunotherapy. Both drugs are approved for use in the US by the Food and Drug Administration (FDA) for use in the treatment of different types of cancer, and nivolumab is approved for use in head and neck cancer that has previously been treated with chemotherapy. Because they are not approved to be used together in HPV-associated head and neck cancer, these drugs are considered experimental in this study. For this study, the drugs will be used either together or separately.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on full-dose anticoagulation or have certain medical conditions, you may not be eligible to participate.

What data supports the effectiveness of the drug combination 5-azacytidine and nivolumab for squamous cell carcinoma?

Nivolumab has been shown to improve survival and quality of life in patients with recurrent squamous-cell carcinoma of the head and neck, and it has also been effective in treating advanced squamous non-small cell lung cancer. This suggests that nivolumab may be beneficial in treating squamous cell carcinoma when combined with other drugs like 5-azacytidine.12345

Is the combination of 5-Azacytidine and Nivolumab safe for humans?

Nivolumab, used in various cancer treatments, has a manageable safety profile, though it can cause immune-related side effects. While specific safety data for the combination with 5-Azacytidine is not provided, Nivolumab alone has been generally well-tolerated in studies for other cancers.34678

How is the drug combination of 5-azacytidine and nivolumab unique for treating squamous cell carcinoma?

The combination of 5-azacytidine and nivolumab is unique because it combines a drug that modifies DNA (5-azacytidine) with an immune system booster (nivolumab), potentially offering a new approach for squamous cell carcinoma, especially when other treatments have limited options or high side effects.137910

Research Team

Barbara Burtness, MD < Yale School of ...

Barbara Burtness, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults with resectable HPV-associated squamous cell carcinoma of the oropharynx, without prior systemic therapy or radiation. Participants must have certain blood counts and organ function levels within normal ranges, not be on full dose anticoagulation, and women must not be pregnant or breastfeeding.

Inclusion Criteria

Willing and able to provide written informed consent
My biopsy samples are large enough for research, matching or exceeding the size of three 3mm biopsies.
I have a type of throat cancer that can be surgically removed.
See 12 more

Exclusion Criteria

I cannot have surgery through the mouth due to health reasons.
I am on a full dose of blood thinner medication.
I am unable to understand and agree to the study's details.
See 4 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive pre-operative treatment with 5-azacytidine alone, nivolumab alone, or the combination of both drugs

2-3 weeks
Multiple visits for drug administration

Surgery

Surgery is performed to resect the tumor

1 week
In-person surgical visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
2 visits (in-person)

Treatment Details

Interventions

  • 5-azacytidine (Chemotherapy)
  • Combination 5-azacytidine and nivolumab (Chemotherapy; Checkpoint Inhibitor)
  • Nivolumab (Checkpoint Inhibitor)
Trial OverviewThe study tests if 5-Azacytidine (a chemotherapy drug) can make head and neck cancer more responsive to Nivolumab (an immunotherapy). Patients will receive either one of these drugs alone or in combination to assess their effectiveness against this type of cancer.
Participant Groups
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm C: Combination 5-azacytidine and NivolumabExperimental Treatment1 Intervention
Patients will receive 5-azacytidine 75mg/m2 IV daily x 5. Treatment must begin on a Monday. 5-azacytidine will be given prior to nivolumab on day 2. Patients will receive anti-emetic premedication with prochlorperazine 10 mg IV, a 5HT3 antagonist per institutional guidelines, aprepitant or fos-aprepitant, and prn lorazepam on day 1. Day 2-5 patients will receive prochlorperazine 10 mg IV. Subsequent day 5HT3 antagonist therapy will be determined per institutional guidelines, as recommendations vary based on the half-life of the agent chosen. PRN lorazepam can be used days 2-5. Nivolumab will be administered at a dose of 240 mg IV day 2 and day 16. No additional premedication will be given on day 16. Dexamethasone will be reserved for patients whose nausea and/or emesis is not controlled by the initial regimen. Surgery will be scheduled in the period of day 17 through day 18.
Group II: Arm A: 5-azacytidineActive Control1 Intervention
Patients will receive 5-azacytidine 75mg/m2 IV daily x 5. Treatment must begin on a Monday. Patients will receive anti-emetic premedication with prochlorperazine 10 mg IV, a 5HT3 antagonist per institutional guidelines, aprepitant or fos-aprepitant, and prn lorazepam on day 1. Day 2-5 patients will receive prochlorperazine 10 mg IV. Subsequent day 5HT3 antagonist therapy will be determined per institutional guidelines, as recommendations vary based on the half-life of the agent chosen. PRN lorazepam can be used days 2-5. Dexamethasone will be reserved for patients who are not controlled by the initial regimen. A single cycle of 5-azacytidine will be administered and the patient scheduled for surgery in the period of day 16 through day 18.
Group III: Arm B: NivolumabActive Control1 Intervention
Nivolumab will be administered at a dose of 240 mg IV day 1 and day 15. Treatment must be given on a Monday or Tuesday. No premedication will be given. Patients will be observed following the initial dose of nivolumab per institutional Surgery will be scheduled in the period of day 16 through day 18.

5-azacytidine is already approved in Canada, Japan for the following indications:

🇨🇦
Approved in Canada as Vidaza for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia
🇯🇵
Approved in Japan as Azacitidine for:
  • Myelodysplastic syndromes
  • Acute myeloid leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

Barbara Burtness

Lead Sponsor

Trials
1
Recruited
50+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials
312
Recruited
853,000+
Janice S. Lee profile image

Janice S. Lee

National Institute of Dental and Craniofacial Research (NIDCR)

Clinical Director

DDS, MD, MS

Jennifer Webster-Cyriaque profile image

Jennifer Webster-Cyriaque

National Institute of Dental and Craniofacial Research (NIDCR)

Acting Director

DDS, PhD

Findings from Research

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.
The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.
Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis.Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]
Nivolumab treatment resulted in an increased overall survival rate of 7.5 months compared to 5.1 months for the control group, indicating its efficacy in extending life for patients.
Patients receiving nivolumab also reported a better quality of life, suggesting that the treatment not only prolongs survival but also improves the well-being of those undergoing therapy.
Nivolumab for recurrent squamous-cell carcinoma of the head and neck.[2018]
Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.
Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.
Nivolumab: a review in advanced squamous non-small cell lung cancer.Keating, GM.[2022]

References

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]
Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]
Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]
Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study. [2023]
Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]
First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]
Clinical Remission of Cutaneous Squamous Cell Carcinoma of the Auricle with Cetuximab and Nivolumab. [2020]
Squamous cell carcinoma or squamous proliferation associated with nivolumab treatment for metastatic melanoma. [2022]
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. [2022]
[Regression of cutaneous basal cell and squamous cell carcinoma under pembrolizumab]. [2020]