Concurrent Immunotherapy With Postoperative Radiotherapy in Intermediate/High Risk HNSCC Patients Unfit for Cisplatin: The IMPORT Study (IMPORT)

Study Overview
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Brief Summary
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To investigate weather concurrent JS001 with postoperative radiotherapy would have survival benefit in intermediate/high Risk HNSCC Patients who cannot take cisplatin

Official Title
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Randomized Phase II Trial of Postoperative Radiotherapy With Concurrent JS001（PD-1 Antibody） vs. Postoperative Radiotherapy Alone in Intermediate/High-risk Head and Neck Cancer Patients With a Contraindication to Cisplatin

Conditions
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Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Radiation: postoperative radiotherapy
* Drug: JS001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Histologically confirmed squamous cell carcinoma of the head and neck.Site of tumor origin in the oral cavity, oropharynx, larynx, hypopharynx , or sinuses (excluding nasopharynx) 2. With at least one risk factors after radical surgery ①positive margin; ②close margin（<5mm); ③ENE;④PNI;⑤LVI; ⑤ pT3-4/N2-3( AJCC 8th).⑥ Level IV/V lymph node metastases for OPC or OC. 3. Have at least one contraindication to cisplatin as defined: ① Age>65 years old; ②Creatinine clearance (CC) > 30 and < 60 cc/min For this calculation, use the Cockroft-Gault formula: CC = 0.85 (if female)* ((140-Age) / (Serum Creatinine)) * (Weight in kg / 72); ③ Zubrod performance status 2; ④Pre-existing peripheral neuropathy grade ≥ 1; ⑤History of hearing loss, defined as either: ▪ Existing need of a hearing aid OR ≥ 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated. 4. No distant metastases 5. No synchronous or concurrent head and neck primary tumors 6. ECOG PS 0-2 7. Adequate organ function including the following: Absolute neutrophil count (ANC) >= 1.5 * 10^9/l Platelets count >= 80 * 10^9/l Hemoglobin >= 80 g/dl AST and ALT <= 2.5 times institutional upper limit of normal (ULN) Total bilirubin <= 1.5 times institutional ULN Creatinine clearance >30 ml/min 8. Signed written informed consent Exclusion Criteria: Prior chemotherapy or anti-cancer biologic therapy for any type of cancer, or prior radiotherapy to the head and neck region Other previous cancer, except for in situ cervical cancer and cutaneous basal cell carcinoma Pregnant or breast-feeding females, or females and males of childbearing potential not taking adequate contraceptive measures Uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia Active, known or suspected autoimmune disease such as interstitial pneumonia, uveitis, Crohn's disease, autoimmune thyroiditis. Subjects with cured childhood asthma, type I diabetes mellitus and hypothyroidism only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment Using systemic immunosuppressive agents and continue the dose within 2 weeks prior to the enrollment;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: concurrent PD-1<br>Concurrent Immunotherapy With Postoperative Radiotherapy | Radiation: postoperative radiotherapy<br>* postoperative radiotherapy with a dose of 60-66Gy<br>Drug: JS001<br>* JS001 240mg every three week<br>* Other names: Toripalimab;|
| Active Comparator: Radiotherapy alone<br>Postoperative Radiotherapy alone | Radiation: postoperative radiotherapy<br>* postoperative radiotherapy with a dose of 60-66Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival |  | from date of enrollment until date of first documented disease progression or death from any cause, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | from date of enrollment until death from any cause, assessed up to 2 years | 
| Number of participants with treatment-related acute toxicity as assessed weekly by CTCAE v4.0 during the course of treatment | Acute toxicity profiles, graded according to the NCI CTCAE version 4.0 | up to 3 months after completion of radiotherapy | 
| Number of participants with treatment-related late toxicity as assessed by CTCAE v4.0 | Late toxicity profiles, graded according to the NCI CTCAE version 4.0 | from 3 months after completion of radiotherapy up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and neck cancer, radiotherapy, PD-1