1. Primary Objective: \- Major pathologic response rate defined by ≤ 10% of tumor composed of viable tumor 2. Secondary Objectives: * Complete resection rate * Response rate to neoadjuvant therapy according to RECIST 1.1 * Downstaging at pathologic staging compared to clinical staging performed at study entry * Distant metastasis free survival (DMFS) rate at 2 years * Disease free survival at 2 years * Overall survival rate at 2 years * Safety and feasibility 3. Exploratory Objectives: * PD L1 expression by 28-8 immunohistochemistry * IHC (HER2, AR, etc) * Whole exome sequencing (WES) * Whole transcriptome sequencing (WTS) * Peripheral blood biomarkers (CD4+ T cells, CD8+ T cell, myeloid derived suppressor cells (MDSC), Treg etc) * Interferon gamma related gene expression profile * Multiplex florescence measure of tumor cells and tumor microenvironment cells
This is a phase II, single center, open-label, single arm study in patients with resectable, high grade salivary gland carcinoma. Patients will be treated with nivolumab 360mg and plus docetaxel 60mg/m2 and cisplatin 60mg/m2 every 3 weeks for 3 cycles and will be evaluated for the operability. Patients with R0 resection will receive radiation 59.4 Gy in 27 fractions. Boost RT of 6.6 Gy in 3 fractions to tumor bed and/or gross tumor will be optional in patients who had R1-R2 resection. If tumors are regarded inoperable after neoadjuvant therapy (due to high risk of post-operative complication, or metastatic disease), they will be off from this study and receive the appropriate treatment, though they will be also included in the efficacy and safety analyses.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Patients will be treated with nivolumab 360mg and plus docetaxel 60mg/m2 and cisplatin 60mg/m2 every 3 weeks for 3 cycles and will be evaluated for the operability. Patients with R0 resection will receive radiation 59.4 Gy in 27 fractions. Boost RT of 6.6 Gy in 3 fractions to tumor bed and/or gross tumor will be optional in patients who had R1-R2 resection. If tumors are regarded inoperable after neoadjuvant therapy (due to high risk of post-operative complication, or metastatic disease), they will be off from this study and receive the appropriate treatment, though they will be also included in the efficacy and safety analyses.
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
Seoul, South Korea
RECRUITINGMajor pathologic response rate defined by ≤ 10% of tumor composed of viable tumor
Primary tumors were assessed for the percentage of residual viable tumor that was identified on routine hematoxylin and eosin staining, and tumors with no more than 10% viable tumor cells were considered to have had a major pathological response. Patients who have progressive disease after neoadjuvant therapy and drop out from the study population will be counted as patients without major pathologic response.
Time frame: 6 months
Complete resection rate
Complete resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. Complete resection rate is defined as the percentage of the patients that underwent a resection and had a microscopically complete (or R0) resection.
Time frame: Up to 24 months
Response rate to neoadjuvant therapy according to RECIST 1.1
RECIST 1.1 will be used as the primary measure for assessment of tumor response, date of disease progression, and as a basis for all protocol guidelines related to disease status (eg, discontinuation of study treatment).
Time frame: Up to 24 months
Downstaging at pathologic staging compared to clinical staging performed at study entry
Downstaging defined as pathologic TNM less than clinical TNM. Cancer staging calculator(AJCC 8th Edition)
Time frame: Up to 24 months
Distant metastasis free survival (DMFS) rate at 2 years
Distant metastases free survival (DMFS) is defined as the time between date of enrollment and the date of first diagnosis of distant metastasis or death, whichever comes first. Patients in whom distant metastases are discovered during neoadjuvant chemo/immunotherapy or the evaluation thereafter or at the immediate surgery, are considered to have an event at that time point.
Time frame: Up to 24 months
Disease free survival at 2 years
Patients that have undergone a resection and are alive without distant metastases (regardless of locoregional failure) are censored at the last date available.
Time frame: Up to 24 months
Overall survival rate at 2 years
Overall survival (OS) and is defined as the time between date of enrollment and date of death from any cause. Patients alive at last follow-up are censored at the last date available.
Time frame: Up to 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Who dose discontinued due to adverse event.
Time frame: Up to 24 months
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