An Open Label, Two Arm Phase II Study of Toripalimab Versus Toripalimab in Combination With Carboplatin and Nab-paclitaxel as a Novel Neoadjuvant Pre-Surgical Therapy for HNSCC
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 57
- Locations
- 1
- Primary Endpoint
- Percentage of participants demonstrating pathological response
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This proposed study will evaluate the efficacy and safety of preoperative administration of Toripalimab or Toripalimab combined with nab-paclitaxel and carboplatin in Head and Neck Squamous Cell Carcinoma (HNSCC) who are about to undergo surgery，and it will be helpful for comprehensive exploratory characterization of tumor immune microenvironment and circulating immune cells in these patients. Data obtained in this trial will provide valuable information for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in HNSCC. We are also eager to identify potential biomarkers of response and toxicity that will enable patients with HNSCC who are most likely to benefit to receive anti-PD-1 therapy and, to the contrary, reduce the risk of toxicity and ineffective therapy in patients who are less likely to benefit from it.
Investigators
Song Fan, MD
Associate Professor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Eligibility Criteria
Inclusion Criteria
- •Have a histologically confirmed diagnosis of HNSCC which is planned for treatment with curative intent including surgical resection.
- •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 , anti-programmed cell death 1, anti-programmed cell death 1 ligand 1 , 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
Toripalimab (IV), dose= 240mg , day=1 , cycle length: 21 days
Intervention: Toripalimab
Toripalimab
Toripalimab (IV), dose= 240mg , day=1 , cycle length: 21 days
Intervention: Surgical resection
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, nab-paclitaxel, carboplatin
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: Surgical resection
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
- Pathologic Response(6 weeks)
- Overall survival（OS）(5 years)
- Disease-free survival （DFS）(2 years)
- Radiographic Response(5 weeks)
- Rate of surgery delay(8 weeks after the patient receives their last dose)