Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Oral Squamous Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Histone Deacetylase Inhibitors

Mocetinostat

Antineoplastic Agents, Immunological

Enzyme Inhibitors

Patients will start therapy with mocetinostat within 10 days of study enrollment. Mocetinostat will be given in 2 dose levels (n = 6 evaluable patients each) of 70mg three-times weekly and 90mg three-times weekly for 2 weeks.

Durvalumab will be given as a single infusion at a dose of 1500mg, over a period of 1-hour, on day 8 of the study.

Mocetinostat (MGCD0103) is a potent small molecule HDAC inhibitor that targets human HDAC isoforms. It is an orally bioavailable, second generation benzamide inhibitor of HDAC 1, 2, 3 and 11 with broad spectrum antitumor activity in vitro and in vivo.

Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody directed against human PD-L1. It is selective for recombinant PD-L1 and blocks the binding of recombinant PD-L1 to the PD-1 and CD80 receptors.

Lillian Siu, MD

This is a Phase 1 Window of Opportunity study to evaluate the pharmacodynamic and immune effects of pre-operative therapy with Mocetinostat and Durvalumab on patients with squamous cell carcinoma of the oral cavity.

This is a single center, open-label, non-randomized, pre-operative window of opportunity study for patients with resectable squamous cell carcinoma of the oral cavity who are considered suitable for curative-intent surgical resection, with pre-operative Mocetinostat and Durvalumab.

This study will involve treatment with Mocetinostat and Durvalumab, tests and procedures done for safety and the collection of blood samples for biomarker research. Tissue samples (fresh biopsy or archival tissue) will also be collected for biomarker research and evaluation.

Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity

Mirati Therapeutics Inc.

AstraZeneca

University Health Network, Toronto

Mouth and Tooth Diseases

Mouth Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Cancer

Vasoconstrictor Agents

Central Nervous System Depressants

Amino Acids

Nivolumab

Cocaine

Immune Checkpoint Inhibitors

Tyrosine

Patients will start therapy with sitravatinib within 10 days of study enrollment. Sitravatinib will be given at 120mg once daily on a continuous basis until 48 hours before planned surgery, or for a maximum period of 28 days.

Nivolumab will be given as a single infusion at a dose of 240mg, over a period of 30 minutes on Day 15 of the study.

Sitravatinib (MGCD516) is an orally-available, potent small molecule inhibitor of a closely related spectrum of tyrosine kinases, which has shown antitumor activity in a variety of in vitro and in vivo model systems.

Sitravatinib

Nivolumab (OPDIVO®) is a human IgG4 kappa immunoglobulin that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

This is a window of opportunity study for patients with resectable squamous cell carcinoma of the oral cavity who are considered suitable for curative-intent surgical resection, with pre-operative drugs, Sitravatinib and Nivolumab.

This is a single center, open-label, non-randomized, pre-operative window of opportunity study for patients with resectable squamous cell carcinoma of the oral cavity who are considered suitable for curative-intent surgical resection, with pre-operative Sitravatinib and Nivolumab. A total of 12 patients who are evaluable for correlative studies, are planned for enrollment.

This study will involve treatment with Sitravatinib and Nivolumab, tests and procedures done for safety and the collection of blood samples for biomarker research. Tissue samples (fresh biopsy or archival tissue) will also be collected for biomarker research and evaluation.

Sitravatinib (MGCD516) and Nivolumab in Oral Cavity Cancer Window Opportunity Study

Sitravatinib (MGCD516) and Nivolumab in Oral Cavity Cancer Window Opportunity Study (SNOW)

Additional tumor cell surface marker expression

Flow cytometry analysis of activation markers on circulating immune cells

Tumor and immune cell genome and transcriptome analysis

Analysis of tumor 18FAZA-PET uptake patterns

Density of immune cell population in the tumor and/or peripheral blood, including circulating tumor DNA (ctDNA), T-cell subsets, NK cells and myeloid-derived cell subsets

Serum pro-inflammatory cytokines and chemokines

Rate of completion of surgery within the initially planned window

Rate of disease progression as per RECIST v1.1 during the pre-operative treatment period

Pathologic treatment effect in tumor and/ or lymph nodes

Rate of nodal extracapsular extension and positive margins

Analysis of plasma Sitravatinib concentration before and after Nivolumab therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity	NCT02993991	Squamous Cell C... Squamous Cell C... Resectable Squa...	Mocetinostat Durvalumab	18 Years -	University Health Network, Toronto
Sitravatinib (MGCD516) and Nivolumab in Oral Cavity Cancer Window Opportunity Study	NCT03575598	Squamous Cell C... Squamous Cell C... Squamous Cell C...	Sitravatinib Nivolumab	18 Years -	University Health Network, Toronto

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