Clinical trial NCT04624308: Toripalimab Plus TPF Chemotherapy and Radiotherapy for LA-HPSCC
Official title: Toripalimab Plus TPF Inductive Chemotherapy and Definitive Radiotherapy for Resectable Locally Advanced Hypopharyngeal Squamous Cell Carcinoma, Efficacy and Safety: a Phase II Prospective Cohort Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hypopharyngeal Neoplasm Malignant Primary
Keywords: hypopharyngeal carcinoma
radiotherapy
inductive chemotherapy
PD-1 inhibitor
Lead sponsor: Peking University
Sponsor class: OTHER
Collaborators: name: Shanghai Junshi Bioscience Co., Ltd.
First posted: 2020-11-10
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TPF is the standard regime of inductive chemotherapy for squamous carcinoma of head and neck. If the primary tumor shrinks obviously (complete remission or \>75% partial remission )after inductive chemotherapy, CCRT is suggested as the definitive therapy, for the tumor is sensitive to chemotherapy. If the primary tumor shrinks a little or progresses after inductive chemotherapy, operation is suggested as the definitive therapy to get a longer survival.

Detailed description: Inductive chemotherapy plus CCRT or operation is an option of organ preservation for patients of hypopharyngeal carcinoma. Many clinical studies have demonstrated that inductive chemotherapy plus CCRT achieved the same prognosis as total laryngectomy, and minimized the damage of normal tissue. TPF is the standard regime of inductive chemotherapy for squamous carcinoma of head and neck. If the primary tumor shrinks obviously (complete remission or \>75% partial remission )after inductive chemotherapy, CCRT is suggested as the definitive therapy, for the tumor is sensitive to chemotherapy. If the primary tumor shrinks a little or progresses after inductive chemotherapy, operation is suggested as the definitive therapy to get a longer survival. This is a prospective, phase II, cohort study. We designate TPF plus Toripalimab as the inductive regime, expecting a higher complete remission rate and longer PFS and OS. And we replace the CCRT with radiation plus Toripalimab to decrease the adverse events of CCRT.

Eligibility criteria: Inclusion Criteria:

1. 18y ≤age≤65y;
2. ECOG：0-1；
3. Histology：squamous cell carcinoma, located in hypopharynx;
4. clinical stage: cT1N1-3M0、cT2-3N0-3M0，organ-preservation-intent regime is made after multidisciplinary treatment(MDT) discussion. Efficacy evaluation will be made according to RECIST 1.1 after inductive chemotherapy, and the following treatment will be chosen according to the results of efficacy evaluation.
5. never received any previous treatment, including radiotherapy, chemotherapy, or immune therapy, et al.
6. at least one measurable lesion (RECIST 1.1 criteria).
7. expected survival ≥6 months.
8. no contraindications of radiotherapy, chemotherapy and immune therapy.
9. functions of main organs A. WBC≥3.0x109 /L，ANC≥1.5x109/L B. HB≥90g/L C. PLT≥100x109 /L D. serum albumin≥2.8g/dL E. TBil ≤1.5xULN，ALT、AST≤3.0xULN F. serum creatinine ≤1.5xULN or creatinine clearance rate\>60mL/min（Cockcroft-Gault） G. APTT and INR ≤1.5xULN
10. contraception
11. voluntary and compliance.

Exclusion Criteria:

1. other histology cancers located in hypopharynx.
2. synchronous or metachronous cancers located in other sites.
3. allergy to monoclonal antibody.
4. uncontrollable heart disease or symptoms.
5. uncontrollable infections.
6. fever of unknown origin\>38.5℃ during screening or before administration.
7. active autoimmune disease.
8. history of immunodeficiency disorders, including HIV.
9. active HBV or HCV.
10. history of interstitial lung disease.
11. active tuberculosis.
12. received any drugs listed below: A. received any study drug 4 weeks before first dose of Toripalimab. B. received any anti-cancer drug 4 weeks before first dose of Toripalimab. C. received any glucocorticoids （\>10mg prednison per day） 2 weeks before first dose of Toripalimab.

    D. received any cancer vaccine 4 weeks before first dose of Toripalimab. E. received any operation or trauma 4 weeks before first dose of Toripalimab. F. recruited in other study.
13. uncontrollable hypertension.
14. uncontrollable type 2 diabetes；
15. hemorrhagic tendency.
16. drug or alcoholic abuse.
17. woman during pregnancy or lactation period.

Primary outcomes:
measure: Complete remission rate
timeFrame: 3 months after treatment
Secondary outcomes:
measure: ORR
timeFrame: 3 months after treatment
measure: DCR
timeFrame: 5 year
measure: PFS
timeFrame: 5 year
measure: OS
timeFrame: 5 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Yan Sun, MD
role: PRINCIPAL_INVESTIGATOR
References: