Phase II Trial of Toripalimab, an Anti-PD-1 Monoclonal Antibody, in Combination With Combination Carboplatin and Nab-paclitaxel , as a Novel Neoadjuvant Pre-Surgical Therapy for Salivary Gland Malignant Neoplasms
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab , Carboplatin, Nab-paclitaxel
- Conditions
- Salivary Gland Malignant Neoplasms
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Percentage of participants demonstrating pathological response
- Status
- Not yet recruiting
- Last Updated
- 5 years ago
Overview
Brief Summary
This proposed study will evaluate the efficacy and safety of preoperative administration Toripalimab combined with nab-paclitaxel and carboplatin in salivary gland malignant neoplasms who are about to undergo surgery.Monoclonal antibodies, such as Toripalimab , may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.This trial will be helpful for comprehensive exploratory characterization of tumor immune microenvironment and circulating immune cells in these patients.
Investigators
Song Fan, MD
Associate Professor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Eligibility Criteria
Inclusion Criteria
- •Patients must have a histologically confirmed diagnosis of salivary gland cancers which is planned for treatment with curative intent including surgical resection: mucoepidermoid carcinoma, adenocarcinoma, adenoidcystic carcinoma, acinic cell carcinoma, or other histology .
- •Greater than or equal to 18 and less than 80 years of age at time of study entry.
- •ECOG performance status of 0 or
- •Measurable disease as per RECIST 1.
- •Patients must have no prior exposure to immune-mediated therapy, including anti- cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-programmed cell death 1, anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines.
- •Screening labs must meet the following criteria and must be obtained within 14 days prior to registration:
- •Adequate hepatic and renal function as demonstrated by
- •Serum creatinine \< 1.5 X ULN or CrCl \> 40mL/min (if using the Cockcroft-Gault formula below):
- •Males: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum creatinine (mg/dL)）
- •Females: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum creatinine (mg/dL))x 0.85
Exclusion Criteria
- •Is currently participating in or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •Has had another known invasive malignancy within the previous 5 years and/or has had surgery, chemotherapy, targeted small molecule therapy or radiation therapy within 5 years for a known malignancy prior to study day
- •If subject received major surgery for any other reason, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day -
- •Inhaled or topical steroids, and adrenal replacement steroid \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- •Has an active autoimmune disease requiring systemic steroid treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids.
- •Active, known or suspected autoimmune disease. Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger .
- •Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- •Has an active infection requiring systemic therapy.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
Arms & Interventions
Toripalimab + Carboplatin + Nab-paclitaxel
* Toripalimab (IV), dose= 240mg , day=1 , cycle length: 21 days. * Carboplatin (IV), dose=300mg/m2, day= 1, cycle length: 21 days. * Nab-paclitaxel (IV), dose=260mg/m2, day= 1, cycle length: 21 days.
Intervention: Toripalimab , Carboplatin, Nab-paclitaxel
Outcomes
Primary Outcomes
Percentage of participants demonstrating pathological response
Time Frame: At time of surgery
Pathologic response in the primary tumor was assessed using a quantitative grading scheme: pathologic tumor response \[nonviable tumor\] PTR0 = no or \<10% PTR1 = ≥10% PTR2 = ≥50%
Adverse events graded by CTCAE v5.0
Time Frame: 90 days after the first dose of study treatment
Percentage of adverse events that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0).
Secondary Outcomes
- Disease-free survival （DFS）(2 years)
- Overall survival（OS）(5 years)
- Radiographic Response(5 weeks)
- Rate of surgery delay(8 weeks after the patient receives their last dose)
- Pathologic Response(6 weeks)