5-Azacytidine and/or Nivolumab in Resectable HPV-Associated HNSCC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBarbara Burtness
About 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with resectable squamous cell carcinoma of the oropharynx. Histologic or cytologic confirmation from either a biopsy/aspirate of the oropharyngeal primary lesion and/or a regional lymph node is required.
T1-T3, N0-N2, M0 stage by AJCC 8th edition for HPV-initiated oropharynx cancer.
Resectability confirmed by a surgical co-investigator; evaluation may include operative endoscopy to discover second primaries and map tumor extent with biopsy
In addition to diagnostic biopsies, biopsies in clinic or at the time of operative endoscopy are required to yield primary tumor for research purposes > 3mm cup forceps biopsies X 3. Prior biopsies for research obtained with informed consent for the Yale Biosample Repository Protocol are acceptable if they meet the volume requirements above.
Disqualifiers
Medical contraindication to transoral surgery.
Full dose anticoagulation.
Concomitant invasive malignancy, or malignancy within 2 years except for hormonally responsive breast or prostate cancer, resected non-melanoma skin cancer, resected uterine cervical carcinoma or meningioma.
Inability to give informed consent.
Trial design
Design model
Parallel
Treatments tested in this trial
Combination 5-azacytidine and nivolumab
DrugThe primary objective of the study is to determine whether exposure to the demethylating agent 5-azacytidine will sensitize HPV-associated oropharynx cancer to nivolumab by induction of interferon response, neoantigen expression, and augmentation of lymphocyte infiltration of the tumor microenvironment.
Nivolumab
DrugImmunotherapy is a type of treatment that uses your body's own immune system to help fight cancer. Specifically, Nivolumab belongs to a class of anti-cancer drugs known as immune checkpoint inhibitors. Cancer cells are able to "turn off" the immune system by increasing the production of a protein called PD-1. Nivolumab can block PD-1 and may be able to re-activate the immune response to kill head and neck cancer cells.
Treatment groups
50 Participants
are divided into 2 treatment groupsGroup A: Arm B: NivolumabActive comparator 1 intervention
Group B: Arm C: Combination 5-azacytidine and NivolumabExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Increased response for combination therapy compared with either monotherapy
As assessed by the ir-PRC of Cottrell.
Time frame
Day 16-18Secondary outcomes
1
Increased activated T cell infiltration in 5-Aza containing arms compared to Nivolumab monotherapy arm
As confirmed by quantitative immunofluorescence for CD3+ cells and granzyme B expression.
Time frame
Day 16-182
Secondary correlative evidence of anti-tumor response
As captured with tumoral Ki-67 and caspase staining on pre- and post-treatment specimens.
Time frame
Screening pre-treatment specimen Day - 8 through day -1; post treatment specimen Day 16-183
Secondary correlative evidence of disease control
As measured by the HPV ctDNA with the NavDx assay
Time frame
baseline; 14-30 days prior to surgery, 30 and 90 days post resection surgery4
Occurrence of toxicity
Adverse Events occurrence (Common Toxicity Criteria for Adverse Events), Immune-related adverse events of special interest, and hyperprogression will be captured.
Time frame
Time of 1st treatment to 30 days postSponsors and contacts
Click on the lead sponsor to view all of their trials.
Barbara Burtness
Lead sponsor
Yale University
Sponsor institution
National Institute of Dental and Craniofacial Research (NIDCR)
Collaborator
Source ClinicalTrials.gov