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.
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, if you are on full-dose anticoagulation or using supraphysiologic systemic corticosteroids, you may be excluded from participating.
What data supports the idea that 5-Azacytidine + Nivolumab for Squamous Cell Carcinoma is an effective treatment?The available research does not provide specific data on the effectiveness of 5-Azacytidine + Nivolumab for Squamous Cell Carcinoma. However, it does show that Nivolumab alone can increase overall survival in patients with recurrent squamous-cell carcinoma of the head and neck, improving survival from 5.1 months to 7.5 months. This suggests that Nivolumab has some effectiveness in treating squamous cell cancers. Additionally, Nivolumab has been shown to be effective in other types of cancer, such as non-small cell lung cancer, where it improved survival and was better tolerated than other treatments. This information might suggest potential benefits when combined with 5-Azacytidine, but specific data for this combination in Squamous Cell Carcinoma is not provided.135910
Is the drug combination of 5-azacytidine and nivolumab promising for squamous cell carcinoma?Yes, the combination of 5-azacytidine and nivolumab is promising for squamous cell carcinoma. Nivolumab has shown success in improving survival rates and achieving remission in various types of squamous cell carcinomas, including those that are difficult to treat with traditional methods. This suggests that the combination with 5-azacytidine could be an effective treatment option.12469
What safety data exists for 5-Azacytidine and Nivolumab in treating Squamous Cell Carcinoma?The safety data for Nivolumab, a PD-1 immune checkpoint inhibitor, indicates it has a manageable safety profile with immune-related adverse events. It has been used in various cancers, including squamous cell carcinoma, with reports of adverse events expanding over time. However, specific safety data for the combination of 5-Azacytidine and Nivolumab in squamous cell carcinoma is not detailed in the provided research.147810
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
I have a type of throat cancer that can be surgically removed.
I am older than 18 years.
My cancer is HPV-related, confirmed by a specific p16 test.
I am fully active or can carry out light work.
My throat cancer is in the early to mid stages and has not spread widely.
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.
I do not have an active autoimmune disease, haven't used high-dose steroids recently, and am not allergic to study drugs.
I have had previous treatments like surgery, radiation, or medication for my cancer.
Treatment Details
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.
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 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 nearbySelect from list below to view details:
Yale UniversityNew Haven, CT
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Who is running the clinical trial?
Barbara BurtnessLead Sponsor
National Institute of Dental and Craniofacial Research (NIDCR)Collaborator
References
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.
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.
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.
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.
Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]Nivolumab plus ipilimumab achieves higher response rates than previously reported for nivolumab alone.
[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.
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
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.
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.
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.