| Eligibility |
Inclusion Criteria:
1. Signing of the informed consent form and willingness to comply with the study
protocol.
2. Age =18 and =75 years.
3. Histologically confirmed laryngeal or hypopharyngeal squamous cell carcinoma.
4. Locally advanced laryngeal/hypopharyngeal cancer patients eligible for surgical
resection (AJCC 8th edition stage: T2N+M0, T3-T4aN0-3M0).
5. Presence of at least one measurable lesion before treatment, in accordance with RECIST
1.1 criteria for "measurable lesions."
6. Patients who have received neoadjuvant immunotherapy combined with chemotherapy and
have achieved a partial response (PR) in the primary lesion according to RECIST 1.1
criteria and are suitable candidates for organ preservation surgery.
7. Expected survival of more than 3 months.
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
9. Good organ function, meeting the following criteria:
1. Absolute neutrophil count (ANC) =1.5×10^9/L.
2. Platelet count =100×10^9/L.
3. Hemoglobin =9 g/dL.
4. Serum albumin =2.8 g/dL.
5. Total bilirubin =1.5× upper limit of normal (ULN), ALT, AST, and/or ALP =3× ULN.
6. Serum creatinine =1.5× ULN and creatinine clearance =60 mL/min (Cockcroft-Gault
formula, see Appendix III).
7. Activated partial thromboplastin time (APTT) and international normalized ratio
(INR) =1.5× ULN (patients on stable doses of anticoagulation with agents like low
molecular weight heparin or warfarin, and INR within the expected therapeutic
range, may be included).
10. Patients with hepatitis B virus (HBV) infection, inactive/asymptomatic HBV carriers,
or patients with chronic or active HBV infection with HBV DNA <500 IU/mL (or 2500
copies/mL) at screening will be allowed to participate. Patients positive for
hepatitis C antibodies, if HCV-RNA is negative at screening, will be allowed to
participate.
11. Females of childbearing potential must have a negative pregnancy test result in urine
or serum =7 days before treatment initiation. They must use a medically accepted
contraceptive measure (such as intrauterine device, oral contraceptives, or condoms)
during the study treatment period, for at least 3 months after the last dose of
toripalimab, and for at least 6 months after the last dose of chemotherapy.
12. Non-sterilized male participants must be willing to use a medically accepted
contraceptive measure (such as intrauterine device, oral contraceptives, or condoms)
during the study treatment period, for at least 3 months after the last dose of
toripalimab, and for at least 6 months after the last dose of chemotherapy.
Exclusion Criteria:
1. History of allergic reactions to any components of toripalimab, paclitaxel, or
cisplatin.
2. Pre-existing tracheostomy due to laryngeal dysfunction before treatment.
3. History of or concurrent presence of other malignancies (except for those cured and
with no cancer-related survival exceeding 5 years, such as basal cell carcinoma of the
skin, cervical carcinoma in situ, and papillary thyroid cancer). Patients with
concurrent hypopharyngeal and esophageal cancers, where the lesions are not
anatomically adjacent, will be diagnosed as having dual primary tumors and will not be
eligible for inclusion.
4. Uncontrolled clinical cardiac symptoms or diseases, including:
1. NYHA Class II or higher heart failure.
2. Unstable angina.
3. Myocardial infarction within the past year.
4. Clinically significant ventricular or supraventricular arrhythmias requiring
clinical intervention.
5. Previous treatment with any of the following:
1. Use of any investigational drug within 4 weeks prior to the first dose of study
treatment.
2. Concurrent participation in another clinical trial, unless it is an observational
(non-interventional) clinical trial.
3. Requiring systemic treatment with corticosteroids (daily dose >10 mg prednisone
equivalent) or other immunosuppressive medications within 2 weeks prior to the
first dose of study treatment, excluding corticosteroids for localized
inflammation or prophylaxis against allergies or nausea/vomiting. Other specific
circumstances should be discussed with the investigator. In the absence of active
autoimmune disease, inhaled or topical steroids and adrenal replacement therapy
with a dose of >10 mg/day prednisone or equivalent are allowed.
4. Vaccination with anti-tumor vaccines or administration of live vaccines within 4
weeks prior to the first dose of study treatment (for patients who received
COVID-19 vaccine, a 2-week interval is required).
5. Major surgery within 4 weeks before the first dose of study treatment or presence
of severe trauma.
6. Failure to recover to = Grade 1 toxicity per CTCAE (except for alopecia and residual
neuropathy related to prior platinum therapy) from previous cancer therapy or from any
other cause unrelated to study/enrollment criteria.
7. Experience of severe infections (CTCAE > Grade 2) within 4 weeks before the first dose
of study treatment, such as severe pneumonia requiring hospitalization, sepsis, or
complicated infections. Baseline chest imaging indicating active pulmonary
inflammation, presence of symptoms and signs of infection within 4 weeks before the
first dose of study treatment, or requirement for oral or intravenous antibiotics to
treat infection are exclusion criteria.
8. Active autoimmune disease or history of autoimmune disease, such as interstitial lung
disease, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
hypothyroidism, including but not limited to these diseases or syndromes. However,
stable dose of thyroid replacement therapy for autoimmune-mediated hypothyroidism is
allowed. Stable dose of insulin for type I diabetes is allowed. Patients with vitiligo
or childhood-onset asthma/allergies requiring no intervention as adults are allowed.
9. History of immune deficiency, including HIV positive test results, other acquired or
congenital immunodeficiency diseases, or history of organ transplantation or
allogeneic bone marrow transplantation.
10. History of interstitial lung disease (excluding radiation pneumonitis not treated with
steroids), non-infectious pneumonitis.
11. Active tuberculosis infection found through medical history or CT scan, or presence of
active tuberculosis infection within the past year prior to enrollment, or history of
active tuberculosis infection more than 1 year ago but not formally treated.
12. Presence of active hepatitis B (HBV DNA =500 IU/mL or 2500 copies/mL) or hepatitis C
(HCV-RNA positive with HCV-RNA levels above the lower limit of detection of the assay)
infection*.
13. Known history of substance abuse, alcohol abuse, or drug addiction.
14. Pregnant or breastfeeding women.
15. Other factors, as judged by the investigator, that may interfere with the
participant's ability to comply with the study requirements or that may jeopardize the
safety of the participant or the quality of the study data, including the presence of
other severe diseases (including mental illness) requiring concurrent treatment,
severe abnormal laboratory values, family or social factors, which might affect
participant safety or data collection.
- For participants who are HBsAg-positive and either HBV DNA-negative or with HBV
DNA <500 IU/mL or 2500 copies/mL, after receiving stable antiviral treatment,
they may be included in this trial (treatment should be ongoing for >2 weeks
before enrollment, and continued for 6 months after the last dose of study
treatment).
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