5-Azacytidine + Nivolumab for Squamous Cell Carcinoma

Recruiting in Palo Alto (17 mi)

Overseen by Barbara 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. ^{1 2 3 4 5}

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. ^{3 4 6 7 8}

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. ^{1 3 7 9 10}

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.

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.

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 Overview The 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

Group I: Arm C: Combination 5-azacytidine and Nivolumab Experimental Treatment 1 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-azacytidine Active Control 1 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: Nivolumab Active Control 1 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 United States, European Union, Canada, Japan for the following indications:

🇺🇸 Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

🇪🇺 Approved in European Union as Azacitidine for:

• Myelodysplastic syndromes
• Acute myeloid leukemia
• Chronic myelomonocytic leukemia

🇨🇦 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

Research Locations Nearby Select from list below to view details:

Yale University New Haven, CT

Who Is Running the Clinical Trial?

Barbara Burtness Lead Sponsor

National Institute of Dental and Craniofacial Research (NIDCR) Collaborator

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023] First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.

2. England pubmed.ncbi.nlm.nih.gov

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018] Increased overall survival with nivolumab albeit only 7.5 months vs 5.1 months, and a better quality of life.

3. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022] Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.

4. United States pubmed.ncbi.nlm.nih.gov

Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study. [2023] Histone deacetylase (HDAC) inhibitors have potential to augment the effectiveness of immune checkpoint inhibitors and overcome treatment resistance. This dose-escalation/expansion study (NCT02805660) investigated mocetinostat (class I/IV HDAC inhibitor) plus durvalumab in patients with advanced non-small cell lung cancer (NSCLC) across cohorts defined by tumor programmed death-ligand 1 (PD-L1) expression and prior experience with anti-programmed cell death protein-1 (anti-PD-1) or anti-PD-L1 regimens.

5. United States pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019] Nivolumab plus ipilimumab achieves higher response rates than previously reported for nivolumab alone.

6. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022] Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or

7. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Remission of Cutaneous Squamous Cell Carcinoma of the Auricle with Cetuximab and Nivolumab. [2020] Cutaneous squamous cell carcinomas (SCC) affecting the regions of the head and neck can be challenging to resect surgically and refractory to chemotherapy or radiation therapy. Consequently; the treatment of squamous cell carcinomas of the skin is a focus of current research. One such advancement is immunotherapy. Herein we describe clinical remission of invasive, poorly differentiated squamous cell carcinoma of the pre-auricular region with external auditory canal involvement using cetuximab, an epidermal growth factor receptor (EGFR) antibody; and nivolumab, a programmed death receptor-1 (PD-1) antibody. Such durable and comprehensive disease resolution demonstrates the therapeutic potential of cetuximab and nivolumab in surgically challenging, treatment-resistant cutaneous squamous cell carcinoma.

8. United States pubmed.ncbi.nlm.nih.gov

Squamous cell carcinoma or squamous proliferation associated with nivolumab treatment for metastatic melanoma. [2022] Nivolumab is a programmed death-1 (PD1) immune checkpoint inhibitor that treats various types of cancers including non-small cell lung carcinoma and melanoma, among others. Although it serves as an effective immunotherapy, there are many associated immune-related adverse events. Even years after the introduction of nivolumab, the breadth of its side effect profile continues to expand. We present a case of squamous cell carcinoma associated with nivolumab treatment for metastatic melanoma.

9. United States pubmed.ncbi.nlm.nih.gov

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. [2022] Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.

10. France pubmed.ncbi.nlm.nih.gov

[Regression of cutaneous basal cell and squamous cell carcinoma under pembrolizumab]. [2020] The recommended treatments for advanced squamous cell carcinoma (SCC) (chemotherapy, radiotherapy, anti-EGFR) and advanced basal cell carcinoma (BCC) (vismodegib and sonidegib) have many side effects. Nivolumab (anti-PD1 antibody) may be used as second-line therapy in SCC of the head and neck. We report the case of a patient with advanced SCC and BCC which regressed under pembrolizumab.