Toripalimab Plus TPF Chemotherapy and Radiotherapy for LA-HPSCC

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypopharyngeal Neoplasm Malignant Primary
• Intervention / Treatment: Drug: Toripalimab

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.

• Study Type: Interventional
• Enrollment (Anticipated): 81
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yan Sun, MD; Phone Number: 0086-10-88196217; Email: lisaysun@139.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TPF inductive chemotherapy plus Toripalimab and radiotherapy plus Toripalimab; TPF inductive chemotherapy plus Toripalimab for 3 cycles, and radiotherapy plus Toripalimab if the inductive treatment efficacy is CR or >75%PR. If not, operation is suggested.	Drug: Toripalimab; Toripalimab 240mg d1，Q3W. Given with TPF during inductive chemotherapy and definitive radiotherapy.; Other Names: Tuoyi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate	Complete remission rate 3 months after treatment	3 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	objective response rate	3 months after treatment
DCR	disease control rate	5 year
PFS	progression free survival	5 year
OS	overall survival	5 year

Collaborators and Investigators

• Sponsor: Sun Yan
• Collaborators: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Principal Investigator: Yan Sun, MD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): October 30, 2020
• Primary Completion (Anticipated): October 30, 2025
• Study Completion (Anticipated): December 30, 2025

Study Registration Dates

• First Submitted: October 31, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: radiotherapy; PD-1 inhibitor; hypopharyngeal carcinoma; inductive chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms; Hypopharyngeal Neoplasms
• Other Study ID Numbers: 2020-JS001-HPSCC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The data is administered by Peking University Cancer Hospital, the investigators need to request related department for sharing IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No