Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity (PRIMED-001)
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|ClinicalTrials.gov Identifier: NCT02993991|
Recruitment Status : Withdrawn (The study has been terminated due to a change in internal prioritization and not due to any safety concerns.)
First Posted : December 15, 2016
Last Update Posted : December 29, 2017
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Carcinoma, Head And Neck Squamous Cell Carcinoma Mouth Resectable Squamous Cell Carcinoma of Oral Cavity||Drug: Mocetinostat Biological: Durvalumab||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity|
|Estimated Study Start Date :||October 10, 2017|
|Actual Primary Completion Date :||December 21, 2017|
|Actual Study Completion Date :||December 21, 2017|
Experimental: Mocetinostat and Durvalumab
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.
Other Name: MGCD0103
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.
Other Name: MEDI4736
- Pharmacodynamic effects with biomarker analyses (Tumor PD-L1 by IHC; Density of peri-tumoral and intra-tumoral CD3, CD4 and CD8-positive lymphocytes; Serum pro-inflammatory cytokines and chemokines) [ Time Frame: 3 years ]
- Immune effects with biomarker analyses (Tumor PD-L1 by IHC; Density of peri-tumoral and intra-tumoral CD3, CD4 and CD8-positive lymphocytes; Serum pro-inflammatory cytokines and chemokines) [ Time Frame: 3 years ]
- Toxicities as per NCI CTCAE v4.1 [ Time Frame: 3 years ]
- Rate of completion of surgery within the initially planned window as per RECIST v1.1 [ Time Frame: 3 years ]
- Rate of disease progression as per RECIST v1.1 during the pre-operative treatment period [ Time Frame: 3 years ]
- Rate of post-operative complications as per NCI CTCAE v4.1 [ Time Frame: 3 years ]
- Optimal biologically active dose of mocetinostat (Correlation of tumor and serum-based assessments with mocetinostat dose levels) [ Time Frame: 3 years ]
- Changes in serum mocetinostat concentrations prior to and following durvalumab therapy [ Time Frame: 3 years ]
- Dynamic changes in immune cell activation and/or suppression using flow cytometry and DNA/RNA sequencing (tumor and immune cell genome and trascriptome analysis) [ Time Frame: 3 years ]
- Dynamic changes in intratumoral hypoxia with pre-operative mocetinostat and durvalumab therapy using 18FAZA PET [ Time Frame: 3 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02993991
|Princess Margaret Cancer Centre|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Lillian Siu, MD||Staff Physician and Medical Oncologist|