Neoadjuvant Toripalimab Plus Nimotuzumab in Primary Limited-Stage Oral Squamous Cell Carcinoma Prior to Radical Therapy：A Single-arm, Phase Ⅱ Study
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab
- Conditions
- Oral Squamous Cell Carcinoma
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 57
- Locations
- 1
- Primary Endpoint
- Major Pathologic response (MPR) rate
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This study aims to investigate the efficacy and safety of neoadjuvant Toripalimab combined with Nimotuzumab in primary limited stage oral squamous cell carcinoma prior to radical therapy.
Detailed Description
The purpose of this study is to investigate the efficacy and safety of neoadjuvant PD-1 inhibitor toripalimab plus nimotuzumab in subjects with primary limited stage, oral squamous cell carcinoma prior to radical therapy. Patients would be treated with neoadjuvant toripalimab plus nimotuzumab for 2 cycles and then received radical surgery or radiotherapy based on the efficacy assessed by investigators per RECIST v1.1.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged ≥18 years old；male or female.
- •Oral squamous cell carcinoma confirmed by cytology or histology. Evaluation by the investigators to confirmed primary limited-stage (clinical stage T1N+M0, T2-4 anyNM0, AJCC 8th) without prior treatment.
- •Patients who are suitable and agree radical therapy.
- •At least 1 evaluable lesion according to RECIST v1.
- •ECOG PS ≤ 1
- •Adequate organ function, defined as achieving the following laboratory test results ≤ 14 days before treatment
- •Patients must meet the following laboratory test results: i. ANC ≥ 1.5 x 10\^9 / L ii. Platelets ≥100 x 10\^9 / L iii. Hb ≥90 g / L Note: Patients must not receive blood transfusion or growth factor within 14 days before blood sample collection due to neutrophil count, platelet, or hemoglobin below study requirements.
- •Renal function requirements within 4 weeks before treatment: Endogenous creatinine clearance ≥ 60 mL / min or more (based on 24-hour urine creatinine calculation or Cockcroft-Gault formula method).
- •Serum total bilirubin ≤ 1.5×ULN (Gilbert syndrome patients can be enrolled if the total bilirubin is \<3 × ULN).
- •AST and ALT ≤ 3 × ULN. If the patient has liver metastases, AST and ALT ≤ 5×ULN
Exclusion Criteria
- •Not suitable for toripalimab or nimotuzumab treatment.
- •Have previously received any treatment for oral squamous cell carcinoma.
- •Patients with evidence of fistula (esophagus / bronchus or esophagus / aorta)
- •Presence of uncontrollable pleural effusion, pericardial effusion, or ascites that require repeated drainage or medical intervention (with clinically significant recurrence requiring additional intervention within 2 weeks after the intervention).
- •Evidence of complete esophageal obstruction that is not suitable for treatment
- •Have been treated with antitumor agents targeted to PD-1, PD-L1 or PD-L
- •Have active meningeal disease or uncontrolled brain metastases.
- •Patients with active autoimmune disease or history of autoimmune diseases may relapse.
- •Note: Patients with the following diseases can be entered for further screening:
- •Controllable type 1 diabetes
Arms & Interventions
Neoadjuvant Toripalimab plus Nimotuzumab
The participants will receive 2 doses of neoadjuvant Toripalimab plus Nimotuzumab, then the participants will take a radical surgery or radiotherapy according to the efficacy assessed by investigator per RECIST1.1
Intervention: Toripalimab
Outcomes
Primary Outcomes
Major Pathologic response (MPR) rate
Time Frame: up to 18 months
MPR rate is defined as the proportion of participants who have achieved major pathological response（on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy and underwent surgery.
Secondary Outcomes
- 2-year progression-free survival rate (PFS)(up to 42 months)
- 2-year disease-free survival rate (DFS)(up to 42 months)
- Objective response rate (ORR)(up to 18 months)
- QoL scores as evaluated by EORTC H&N 35.(up to 42 months)
- 2-year overall survival rate (OS)(up to 42 months)
- Incidence and severity of adverse events as evaluated by NCI-CTCAEv5.0.(up to 18 months)
- Change in PD-L1 expression(up to 42 months)