De-escalated Radiotherapy for Primary Tumor After Neoadjuvant Therapy With Toripalimab Plus Chemotherapy for Nasopharyngeal Carcinoma

March 15, 2024 updated by: Fang-Yun Xie, Sun Yat-sen University
In the IMRT era, patients with stage II-III (AJCC8th) nasopharyngeal carcinoma achieve high local control. However, survivors are increasingly experiencing late radiation-induced toxicities. A previous study found that reducing the radiation dose to the primary site to 60Gy for patients who achieved partial or complete response to induction chemotherapy resulted in a lower rate of late toxicities and an inferior local control rate. The investigators aim to reduce the radiation dose to the primary site for patients after immunochemotherapy, given the potential of neoadjuvant chemotherapy and immunotherapy to increase response rates and long-term survival. The protocol includes participants with stage II-III (AJCC8th), except T2N0M0, to receive three courses of neoadjuvant gemcitabine plus cisplatin and Toripalimab. If the primary tumour regresses by over 75%, de-escalated radiotherapy with 60Gy will be administered, and participants will receive two cycles of cisplatin and three cycles of Toripalimab during the radiotherapy course. Otherwise, participants will receive conventional radiotherapy and concurrent chemotherapy with cisplatin for two cycles as usual. The aim of this study is to investigate the 3-year local control rate and toxicities of de-escalated radiotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

112

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
        • Principal Investigator:
          • Fangyun Xie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Pathologically confirmed nasopharyngeal carcinoma, patients who have not received anti-cancer therapy;
  2. ECOG performance status score (PS score) 0 or 1.
  3. 18-70 years old.
  4. Stage II-III except T2N0M0 (AJCC 8th).
  5. Neutrophil count ≥ 1.5 × 10^9/L, hemoglobin ≥ 90 g/L and platelet count ≥ 100 × 10^9/L.
  6. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN), bilirubin ≤ 1.5 times ULN; Creatinine clearance ≥ 60 ml/min
  7. Patients are required to sign an informed consent form and must be willing and able to comply with the visits, treatment plan, laboratory tests, and other requirements specified in the study protocol

Exclusion Criteria:

Patients will be excluded from the study, if any of the following criteria is met:

  1. Over the age of 70 or under the age of 18.
  2. HBsAg positive and HBV DNA ≥ 1 × 10^3 copies/ml
  3. HCV antibody positive.
  4. Subjects with active, known or suspected autoimmune diseases were excluded from the study. Eligible participants included those with type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not require systemic therapy such as vitiligo, psoriasis, or alopecia.
  5. History of interstitial lung disease;
  6. Receiving systemic sex hormones or other immunosuppressive therapy at equivalent doses ≥ 10 mg prednisone/day within 28 days prior to signing informed consent; Subjects with systemic sex hormone doses ≤ 10 mg prednisone/day or inhaled/topical corticosteroids were eligible.
  7. Received or about to receive live vaccines within 30 days before signing the informed consent form;
  8. Pregnant or lactating women;
  9. Other malignancies within 5 years, except carcinoma in situ, adequately treated non-melanoma skin cancer and papillary thyroid cancer;
  10. Known previous hypersensitivity to macromolecular protein preparations, or to any component of Toripalimab;
  11. Human immunodeficiency virus (HIV) infection.
  12. Other conditions that may affect the safety of subjects or trial compliance as judged by the investigator, including symptomatic heart failure, unstable angina pectoris, myocardial infarction, active infection requiring systemic treatment, mental illness or family and social factors;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: de-escalated radiotherapy
If the primary tumour regresses by over 75% and the level of EBV DNA reduces to zero, a radiation dose of 60Gy will be administered. Additionally, three cycles of Toripalimab (240mg, every three weeks) and two cycles of cisplatin (100mg/m2, every three weeks) will be given during radiotherapy.
Radiation: de-escalated radiotherapy
Enrolled patients receive three courses of induction therapy with gemcitabine and cisplatin, along with Toripalimab. After induction therapy, patients with a tumor volume regression of 75% or more and no detectable EBV DNA will receive de-escalated radiotherapy for the primary tumor with 60 Gy. During radiotherapy, patients will receive Cisplatin 100 mg/m2 every three weeks for two courses and Toripalimab 240 mg every three weeks for three courses. If patients do not achieve complete remission at the end of radiotherapy, 6 Gy will be added to the residual lesions.
Other: conventional radiotherapy
If the primary tumour regresses by less than 75% or if EBV DNA remains above zero, a conventional radiation dose of 70Gy to the primary tumor and two cycles of cisplatin (100mg/m2, every three weeks) will be administered during radiotherapy.
Radiation: conventional radiotherapy
Enrolled patients receive three courses of induction therapy with gemcitabine and cisplatin, along with Toripalimab. After induction therapy, patients with tumor volume regression less than 75% or EBV DNA copy number higher than 0 receive conventional radiotherapy for the primary tumor with 70 Gy. Patients will receive Cisplatin 100 mg/m2, every three weeks for two courses during radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
local recurrence rate(LRR)
Time Frame: 3 years
Defined as the proportion of patients with local recurrence within 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
3-year overall survival
Time Frame: 3 years
3 years
acute and late radiation-induced toxicities
Time Frame: up to 3 years after radiotherapy, respectively
up to 3 years after radiotherapy, respectively
primary tumor volume regression≥75% rate
Time Frame: Two weeks after the third cycle of neoadjuvant immunochemotherapy (each cycle is 21 days), prior to radiotherapy
Two weeks after the third cycle of neoadjuvant immunochemotherapy (each cycle is 21 days), prior to radiotherapy
complete response rate of primary tumor
Time Frame: Two weeks after the third cycle of neoadjuvant immunochemotherapy (each cycle is 21 days) and six months after radiotherapy.
Two weeks after the third cycle of neoadjuvant immunochemotherapy (each cycle is 21 days) and six months after radiotherapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2024

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

March 8, 2024

First Submitted That Met QC Criteria

March 14, 2024

First Posted (Actual)

March 15, 2024

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 15, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2023-110-X02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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