Neoadjuvant Nivolumab, Docetaxel, Cisplatin Therapy Followed by Surgery and Radiation Therapy for Resectable High Grade Salivary Gland Carcinoma

NCT05727410 | Recruiting Phase 2

• 1 other identifier: 2022-02-103
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

• 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
• 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

Conditions

High-grade Salivary Gland Carcinoma

Outcome Measures

Primary Outcomes (1)

• Major 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.

  6 months

Secondary Outcomes (7)

• Complete resection rate

  Up to 24 months

• Response rate to neoadjuvant therapy according to RECIST 1.1

  Up to 24 months

• Downstaging at pathologic staging compared to clinical staging performed at study entry

  Up to 24 months

• Distant metastasis free survival (DMFS) rate at 2 years

  Up to 24 months

• Disease free survival at 2 years

  Up to 24 months

Study Arms (1)

nivolumab, docetaxel, cisplatin Group

EXPERIMENTAL

nivolumab, docetaxel, cisplatin (IV infusion every 3 weeks)

Drug: nivolumab, docetaxel, cisplatin Group

Interventions

nivolumab, docetaxel, cisplatin Group DRUG

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.

nivolumab, docetaxel, cisplatin Group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with histologically- or cytologically-confirmed resectable, clinically node-positive high grade salivary gland carcinoma Adenoid cystic carcinoma: Tubular/cribriform pattern predominant, Solid pattern \> 30% Poorly differentiated carcinoma Mucoepidermoid carcinoma, High grade Polymorphous adenocarcinoma, High grade Lymphoepithelial carcinoma Salivary duct carcinoma Adenocarcinoma, NOS, High grade Carcinosarcoma Squamous cell carcinoma Carcinoma ex pleomorphic adenoma - risk is determined by type of carcinoma and extent of invasion
• No previous chemotherapy treatment history
• Patients who have at least 1 measurable or non-measurable lesion per the RECIST Guideline Ver. 1.1 as confirmed by imaging within 28 days before the first does of investigational product.
• Strongly encourage (but not must) to provide newly obtained core or excisional biopsy of a tumor lesion not previously treated.
• ECOG Performance Status Score 0 or 1
• Patients with a life expectancy of at least 3 months
• Patients whose latest laboratory data meet the below criteria within 28 days before the first dose of the investigational product. If the date of the laboratory tests at the time of enrollment is not within 28 days before the first dose of the investigational product, testing must be repeated within 28 days before the first dose of the investigational product, and these latest laboratory tests must meet the following criteria.
• White blood cells ≥2,000/mm3 and neutrophils ≥1,500/mm3
• Platelets ≥50,000/mm3
• Hemoglobin ≥8.0 g/dL
• AST (GOT) and ALT (GPT) ≤3.0-fold the upper limit of normal (ULN) of the study site
• Total bilirubin ≤1.5-fold the ULN of the study site
• Creatinine ≤1.5-fold the ULN of the study site or creatinine clearance (either the measured or estimated value using the Cockcroft-Gault equation) \>45 mL/min
• Women of childbearing potential (including women with chemical menopause or no menstruation for other medical reasons) #1 must agree to use contraception#2 from the time of informed consent until 5 months or more after the last dose of the investigational product. Women must agree to use contraception#2 from the time of informed consent until 6 months or more after the last dose of docetaxel and 14 months or more after the last dose of cisplatin. Also, women must agree not to breastfeed from the time of informed consent until 5 months or more after the last dose of the investigational product. Women must agree not to breastfeed from the time of informed consent until 1 week or more after the last dose of docetaxel. Cisplatin has been reported to be found in human milk; women must agree not to breastfeed while receiving cisplatin.
• Men must agree to use contraception#2 from the start of study treatment until 7 months or more after the last dose of the investigational product, until 3 months or more after the last dose of docetaxel, and until 11 months or more after the last dose of cisplatin.

You may not qualify if:

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents except patient had no active treatment for past 5 years
• Patients who have received antineoplastic drugs (e.g., chemotherapy agents, molecular-targeted therapy agents, or immunotherapy agents) for high-grade SGC before the first dose of the investigational product
• Has received prior radiotherapy.
• Patients with residual adverse effects of prior therapy or effects of surgery that would affect the safety evaluation of the investigational product in the opinion of the investigator or sub-investigator.
• Patients with concurrent autoimmune disease or history of chronic or recurrent autoimmune disease
• Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment.
• Patients with pericardial fluid, pleural effusion, or ascites requiring treatment
• Patients who have experienced a transient ischemic attack, cerebrovascular accident, or thrombosis within 180 days before enrollment
• Patients with a history of uncontrollable or significant cardiovascular disease meeting any of the following criteria:
• Myocardial infarction within 180 days before enrollment
• Uncontrollable angina pectoris within 180 days before enrollment
• New York Heart Association (NYHA) Class III or IV congestive heart failure
• Uncontrollable hypertension despite appropriate treatment (e.g., systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥ 90 mmHg lasting 24 hours or more)
• Arrhythmia requiring treatment

Sponsors & Collaborators

• Myung-Ju Ahn: lead

Study Sites (1)

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

Seoul, 135-710, South Korea

RECRUITING

MeSH Terms

Interventions

Nivolumab; Docetaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Myung-Ju Ahn, Ph.D.

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Myung-Ju Ahn, Ph.D.

CONTACT

+82-2-3410-1359; silk.ahn@samsung.com

HyeJung Chae

CONTACT

+82-2-3410-1359; hj33.chae@sbri.co.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D, Ph.D. Principal Investigator, Clinical Professor

Model Details: single-center trial

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: February 14, 2023
• Study Start: November 15, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: February 14, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)