Phase II Trial of Sintilimab, an Anti-PD-1 Monoclonal Antibody, in Combination With Reduction of Cycles of Chemotherapy, as a Novel Neoadjuvant Pre-Surgical Therapy for Oral Cavity or Oropharyngeal Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Sintilimab, Nab-paclitaxel, Carboplatin
- Conditions
- Oral Cavity Squamous Cell Carcinoma
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 43
- Locations
- 1
- Primary Endpoint
- pTR-2
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The study is being conducted to evaluate the efficacy and safety of sintilimab in combination with reduction of cycles of chemotherapy (carboplatin and nab-paclitaxel) in patients with oral cavity or oropharyngeal squamous cell carcinoma who are about to undergo surgery. Data obtained in this trial will provide valuable information for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in oral cavity or oropharyngeal squamous cell carcinoma.
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 OSCC or OPSCC 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 (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
Sintilimab+ Carboplatin + Nab-paclitaxel
Neoadjuvant therapy (the total cycles of the treatment is 3) ： Cycle1（Cycle length: 21 days）： Sintilimab (IV), dose= 200mg, day=1; Carboplatin (IV), dose=300mg/m2, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）： Sintilimab (IV), dose= 200mg, day=1. Adjuvant therapy（will be dictated by surgical pathology and occurs after standard of care surgery）： Sintilimab will be given intravenously once every 3 weeks for up to 1 year if participant is considered high-risk based on surgical pathology（high risk features：positive margins or extracapsular extension). These doses of Sintilimab will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.
Intervention: Sintilimab, Nab-paclitaxel, Carboplatin
Sintilimab+ Carboplatin + Nab-paclitaxel
Neoadjuvant therapy (the total cycles of the treatment is 3) ： Cycle1（Cycle length: 21 days）： Sintilimab (IV), dose= 200mg, day=1; Carboplatin (IV), dose=300mg/m2, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）： Sintilimab (IV), dose= 200mg, day=1. Adjuvant therapy（will be dictated by surgical pathology and occurs after standard of care surgery）： Sintilimab will be given intravenously once every 3 weeks for up to 1 year if participant is considered high-risk based on surgical pathology（high risk features：positive margins or extracapsular extension). These doses of Sintilimab will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.
Intervention: Surgical resection
Sintilimab+ Carboplatin + Nab-paclitaxel
Neoadjuvant therapy (the total cycles of the treatment is 3) ： Cycle1（Cycle length: 21 days）： Sintilimab (IV), dose= 200mg, day=1; Carboplatin (IV), dose=300mg/m2, day=1; Nab-paclitaxel (IV), dose=260mg/m2, day=1. Cycle2、3（Cycle length: 21 days）： Sintilimab (IV), dose= 200mg, day=1. Adjuvant therapy（will be dictated by surgical pathology and occurs after standard of care surgery）： Sintilimab will be given intravenously once every 3 weeks for up to 1 year if participant is considered high-risk based on surgical pathology（high risk features：positive margins or extracapsular extension). These doses of Sintilimab will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.
Intervention: Sintilimab
Outcomes
Primary Outcomes
pTR-2
Time Frame: At time of surgery
pTR（pathologic tumor response）was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (\<10%), pTR-1 (10-49%), and pTR-2 (≥ 50%).
Secondary Outcomes
- Adverse events graded by CTCAE v5.0([Time Frame: 90 days after the first dose of study treatment])
- Disease-free survival （DFS）(2 years)
- Radiographic Response(5 weeks)
- Overall survival（OS）(5 years)
- Rate of surgery delay(8 weeks after the patient receives their treatment)