Clinical trial NCT06151743: Neoadjuvant PD-1 Inhibitor Combined With Cetuximab and Platinum in Resectable Locally Advanced Hypopharyngeal Carcinoma
Official title: Neoadjuvant Therapy With Toripalimab Combined With Cetuximab and Platinum for Resectable Locally Advanced Hypopharyngeal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Hypopharyngeal Carcinoma
Lead sponsor: Eye & ENT Hospital of Fudan University
Sponsor class: OTHER
First posted: 2023-11-30
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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:

1. pCR rate
2. MPR rate, ORR, LPR/DFS/OS rare at 1 and 2 years
3. 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.

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;
* Patients who are compliant, willing, and able to follow visiting schedules, treatment plans, laboratory tests, and other research procedures.
* Male and no pregnant female; able to use the contraceptive method during treatment.

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.
* Previously diagnosed immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) - related disease. hepatitis B virus (HBV) surface antigen positive and HBV-DNA ≥ 500 IU/mL (or 2500 copies/mL), or HCV RNA positive. History of active or previous tuberculosis (TB).
* Patients with a history of psychotropic substance abuse who cannot quit or have mental disorders.
* Vaccination within four weeks before enrollment, except for inactivated vaccine.
* Pregnant or lactating women, those who are in the reproductive period and do not use effective contraception;
* Those whom the investigator deems unsuitable to participate in this trial, such as severe acute or chronic medical conditions (including immune colitis, inflammatory bowel disease, non-infectious pneumonia, pulmonary fibrosis) or psychiatric illness (including recent or active suicidal ideation or behavior) or abnormal laboratory tests.

Primary outcomes:
measure: Pathological complete response (pCR) rate after neoadjuvant chemotherapy
timeFrame: Within 3 weeks after surgery
Secondary outcomes:
measure: Major pathologic response (MPR) rate
timeFrame: Within 3 weeks after surgery
measure: Objective response rate (ORR) after neoadjuvant therapy
timeFrame: Up to 14 weeks after the start of neoadjuvant therapy
measure: 1-year and 2-year larynx preservation rate (LPR)
timeFrame: Two years post-radiotherapy
measure: 1-year and 2-year disease-free survival (DFS) rate
timeFrame: Two years post-radiotherapy
measure: 1-year and 2-year overall survival (OS) rate
timeFrame: Two years post-radiotherapy
measure: Adverse Effect
timeFrame: One year post-radiotherapy
Other outcomes:
measure: Quality of Life Score (QoL)
timeFrame: Two years post-radiotherapy
measure: Biomarker detection
timeFrame: Two years post-radiotherapy
Locations:
city: Shanghai
country: China
facility: Eye & ENT Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Eye & ENT Hospital of Fudan University
name: Lei Tao
role: PRINCIPAL_INVESTIGATOR
References: