Trial Title:
Neoadjuvant Nivolumab, Docetaxel, Cisplatin Therapy Followed by Surgery and Radiation Therapy for Resectable High Grade Salivary Gland Carcinoma
NCT ID:
NCT05727410
Condition:
High-grade Salivary Gland Carcinoma
Conditions: Official terms:
Carcinoma
Salivary Gland Neoplasms
Docetaxel
Nivolumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
single-center trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
nivolumab, docetaxel, cisplatin Group
Description:
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.
Arm group label:
nivolumab, docetaxel, cisplatin Group
Summary:
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
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- Women of childbearing potential are defined as all women after the onset of
menstruation who are not postmenopausal and have not been surgically sterilized
(e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy).
Postmenopause is defined as amenorrhea for ≥12 consecutive months without
specific reasons. Women using oral contraceptives, intrauterine devices, or
mechanical contraception such as contraceptive barriers are regarded as having
childbearing potential.
- The subject must consent to use any two of the following methods of
contraception: vasectomy or condom for patients who are male or female
subject's partner and tubal ligation, contraceptive diaphragm, intrauterine
device, spermicide, or oral contraceptive for patients who are female or male
subject's partner.
Exclusion Criteria:
- 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
- Patients with uncontrollable diabetes mellitus
- Patients with systemic infections requiring treatment
- Patients who have received systemic corticosteroids (except for temporary use, e.g.,
for examination or prophylaxis of allergic reactions) or immunosuppressants within
28 days before enrollment
- Patients who have undergone surgical adhesion of the pleura or pericardium within 28
days before enrollment
- Patients who have undergone surgery under general anesthesia within 28 days before
enrollment
- Patients who have undergone surgery involving local or topical anesthesia within 14
days before enrollment
- Patients who have received any radiopharmaceuticals (except for examination or
diagnostic use of radiopharmaceuticals) within 56 days before the first dose of the
investigational product
- Women who are pregnant or breastfeeding, or possibly pregnant
- Patients who have received any other unapproved drug (e.g., investigational use of
drugs, unapproved combined formulations, or unapproved dosage forms) within 28 days
before enrollment
- Patients judged to be incapable of providing consent for reasons such as concurrent
dementia
- Other patients judged by the investigator or sub-investigator to be inappropriate as
subjects of this study
- Patient with current or past history of hypersensitivity to Nivolumab.
- Patients with current or past history of severe hypersensitivity to any other
antibody products
- Patients with a history of (non-infectious) pneumonitis that required steroids or
has current pneumonitis
Gender:
All
Minimum age:
19 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
Address:
City:
Seoul
Zip:
135-710
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Myung-Ju Ahn, M.D.
Phone:
+82-2-3410-3438
Email:
silk.ahn@samsung.com
Start date:
November 15, 2022
Completion date:
August 31, 2026
Lead sponsor:
Agency:
Myung-Ju Ahn
Agency class:
Other
Source:
Samsung Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05727410
