Neoadjuvant Therapy With Toripalimab Combined With Cetuximab and Platinum for Resectable Locally Advanced Hypopharyngeal Cancer
Overview
- Phase
- Phase 2
- Intervention
- three cycles (toripalimab + cetuximab + platinum)
- Conditions
- Locally Advanced Hypopharyngeal Carcinoma
- Sponsor
- Eye & ENT Hospital of Fudan University
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Pathological complete response (pCR) rate after neoadjuvant chemotherapy
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this clinical trial is to evaluate the efficacy and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal cancer. Participants will receive three cycles of TPC neoadjuvant therapy (toripalimab+ cetuximab + platinum), radical surgery (laryngeal preservation surgery if possible), and sequential (chemo)radiotherapy treatment after surgery. This trial aims to answer the following questions:
- pCR rate
- MPR rate, ORR, LPR/DFS/OS rare at 1 and 2 years
- Safety and quality of life
Detailed Description
The standard treatment for patients with resectable hypopharyngeal carcinoma is surgery plus postoperative adjuvant radiotherapy or chemoradiotherapy. Growing evidence shows that neoadjuvant therapy may significantly increase pCR in locally advanced SCCHN patients, potentially improving patient survival. The development of drugs, immunotherapy, and targeted therapy has been proven to improve the overall survival of patients with SCCHN significantly, and PD-1 inhibitor combined with cetuximab has also shown promising efficacy in R/M SCCHN. This study explores the effectiveness and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal carcinoma.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed as hypopharyngeal squamous cell carcinoma;
- •Age between 18-75 years;
- •Patients with resectable locally advanced hypopharyngeal cancer with T3-4aN0-3bM0 (AJCC 8th) require total laryngectomy;
- •Have at least one evaluable target lesion according to RECIST 1.1 criteria.
- •No previous treatment for hypopharyngeal carcinoma;
- •Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-1;
- •Estimated survival ≥ 6 months;
- •Normal organ function;
- •HBV DNA \< 500 IU/mL (or 2500 copies/mL) and HCV RNA negative;
- •Signed informed consent;
Exclusion Criteria
- •Have a history of other cancers in the past five years, except for the following cancers that are cured in the past five years: basal cell carcinoma and squamous cell carcinoma of the skin, early prostate cancer, papillary thyroid cancer, breast ductal carcinoma in situ and cervix carcinoma in situ;
- •The target lesion has been treated with radiation therapy or surgery, except for biopsy to confirm the diagnosis of hypopharyngeal carcinoma;
- •Previous chemotherapy, immunotherapy, or bio-targeted therapy for the primary tumor;
- •Patients who have participated in other clinical trials within four weeks before the trial;
- •Any of the following diseases within six months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
- •Those with hypertension who cannot be reduced to normal range by antihypertensive drugs (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg).
- •Patients with grade I or above coronary heart disease, arrhythmia (including QTc interval prolongation \> 450 ms for men and \> 470 ms for women), and cardiac insufficiency.
- •Patients with positive urine protein (urine protein test 2 + or above, or 24-hour urine protein quantification \>1.0g).
- •Patients with severe allergic history or allergic constitution; an active autoimmune disease that may worsen when receiving immunostimulants. Patients with type I diabetes, vitiligo, psoriasis, or diseases of hypothyroidism or hyperthyroidism that do not require immunosuppressive therapy are eligible to participate in the study.
- •Subjects requiring systemic therapy with corticosteroids (\> 10 mg prednisone or equivalent) or other immunosuppressants within two weeks before the first use of the study drug.
Arms & Interventions
Neoadjuvant therapy+Surgery+Adjuvant therapy
Participants receive three cycles of neoadjuvant therapy (toripalimab+cetuximab+platinum), followed by radical surgery. After surgery, participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation.
Intervention: three cycles (toripalimab + cetuximab + platinum)
Neoadjuvant therapy+Surgery+Adjuvant therapy
Participants receive three cycles of neoadjuvant therapy (toripalimab+cetuximab+platinum), followed by radical surgery. After surgery, participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation.
Intervention: Radical surgery
Neoadjuvant therapy+Surgery+Adjuvant therapy
Participants receive three cycles of neoadjuvant therapy (toripalimab+cetuximab+platinum), followed by radical surgery. After surgery, participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation.
Intervention: Radiotherapy or chemoradiotherapy
Outcomes
Primary Outcomes
Pathological complete response (pCR) rate after neoadjuvant chemotherapy
Time Frame: Within 3 weeks after surgery
The pCR rate is defined as the percentage of participants who have no residual tumor cells in the resected primary tumor within 14 weeks after the start of neoadjuvant therapy.
Secondary Outcomes
- Major pathologic response (MPR) rate(Within 3 weeks after surgery)
- Objective response rate (ORR) after neoadjuvant therapy(Up to 14 weeks after the start of neoadjuvant therapy)
- 1-year and 2-year larynx preservation rate (LPR)(Two years post-radiotherapy)
- 1-year and 2-year disease-free survival (DFS) rate(Two years post-radiotherapy)
- 1-year and 2-year overall survival (OS) rate(Two years post-radiotherapy)
- Adverse Effect(One year post-radiotherapy)