Clinical trial NCT05476965: Selected De-escalation Radiotherapy for Postoperative Head and Neck Squamous Cell Carcinoma
Official title: A Phase II Trial of Cisplatinum, Paclitaxel, and Sintilimab Induction Therapy Followed by De-escalation Radiotherapy for Patients With Postoperative Locally Advanced Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Radiotherapy
Immunotherapy
Surgery
Lead sponsor: Hubei Cancer Hospital
Sponsor class: OTHER
First posted: 2022-07-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is looking to see if sintilimab, an anti-PD-1 McAb given with cisplatinum and paclitaxel (2 chemotherapy agents) during induction therapy in advanced head and neck squamous cell carcinoma can significantly shrink the subject's cancer, then de-escalation radiotherapy can be used.


Eligibility criteria: Inclusion Criteria:

1. Between the age of 18 to 65.
2. Newly diagnosed pathologically confirmed locally advanced head and neck squamous cell carcinoma, including oral cancer, oropharyngeal cancer, laryngeal cancer, while nasopharyngeal carcinoma was excluded. The P16 status of oropharyngeal carcinoma is known.
3. Locally advanced resectable head and neck tumors (stage III and stage IV) were enrolled and radiotherapy is expected to be performed within 4 or 6 weeks after surgery. Tumor staging is based on AJCC/UICC 8th Edition. All the patients must undergo the following examinations to determine the tomor stage before the treatment: complete medical history, physical examination, blood and biochemical routine, head and neck CT or MRI, chest CT scan, abdominal ultrasound and bone scan. In addition, 18F PET/CT can be used to replace the last three imaging examinations mentioned above.
4. ECOG performance status 0 or 1.
5. Normal Organ function

   1. Leukocytes ≥ 4×109/L
   2. Hemoglobin ≥ 90 g/L
   3. Platelets ≥ 100×109/L
   4. Total bilirubin ≤ 1.5x upper limit of normal
   5. Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) ≤ 2.5x upper limit of normal
   6. Alkaline phosphatase ≤ 2.5x upper limit of normal
   7. Creatinine clearance \> 60 mL/min
6. Normal thyroid function, amylase, pituitary function, inflammation and infection index, myocardial enzyme, and ECG. For patients with abnormal ECG or cardiovascular history but not meet the exclusion criteria, a cardiac color ultrasound is needed, and the results should be normal.
7. Patients must sign an informed consent form prior to study entry and they must be willing to comply with the visit, treatment protocol, laboratory examination and other requirements included in the study protocol.
8. Women of childbearing potential and men with fertility partners must agree to follow instructions for methods of contraception (such as condoms or contraceptive drugs) from screening to 1 years after completing treatment.

Exclusion Criteria:

1. Positive HBsAg and HBV DNA \> 1×103 copies/ml, or anti-HCV antibody positive.
2. Positive anti-HIV antibody or diagnosed as AIDS.
3. patients with active tuberculosis history (whether treated or not) in the past 1 years, or with a history of tuberculosis more than 1 years (except those who had received regular anti-tuberculosis treatment).
4. Has active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary diseases, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchiectasis). Type I diabetes, hypothyroidism requiring hormone replacement therapy, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis or alopecia) are not included.
5. Diagnosis of interstitial pneumonia or pneumonia and receiving oral or intravenous steroid therapy in the past 1 year.
6. Receiving systemic glucocorticoid (10 mg prednisone per day) therapy or any other form of immunosuppressive therapy (excluding inhaled or topical corticosteroids).
7. Uncontrolled heart disease, such as: heart failure, NYHA level ≥ 2; instability Angina pectoris; myocardial infarction history in the past 1 year; supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.
8. Pregnant or breastfeeding female patients (women of childbearing potential must have urine pregnancy test).
9. Suffering from other malignant tumors at previously or currently. Additionally, well treated non melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer are not included.
10. Allergic to macromolecular protein or any component of anti-PD1 antibody.
11. Active infection requiring systemic therapy no more than one week.
12. Has received a live vaccine within 30 days before administrating anti-PD-1 antibody.
13. organ transplantation history.
14. Other situations assessed by the investigator that may endanger patient safety or compliance, such as serious diseases requiring treatment (including mental diseases), serious abnormal test results, or with other family or social high-risk factor.

Primary outcomes:
measure: Pathological complete response rate (pCR)
timeFrame: 3 weeks
Secondary outcomes:
measure: Radiation dose of normal organs and treatment-related adverse events
timeFrame: 12 months
measure: Safety of sintilimab in combination with chemotherapy
timeFrame: 12 months
measure: Functional assessment of cancer therapy scale head and neck quality of life assessments
timeFrame: 6 months after the use of anti-PD-1 McAb sintilimab
measure: Progression free survival (PFS) in 2 years
timeFrame: 24 months
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
Study officials:
affiliation: Hubei Cancer Hospital
name: Desheng Hu, Dr.
role: STUDY_CHAIR
References: