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

NCT ID: NCT06313450

Last Updated: 2024-03-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-04
• Study Completion Date: 2028-02-01

Brief Summary

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.

Conditions

Nasopharyngeal Carcinoma; Radiotherapy; Complications; IMMUNOTHERAPY

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

de-escalated radiotherapy

Intervention Type: RADIATION

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.

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.

Group Type: OTHER

conventional radiotherapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: RADIATION

Eligibility Criteria

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Fang-Yun Xie

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Puyun Ouyang

Role: CONTACT

ouyangpy@sysucc.org.cn

+8602087342926

Fangyun Xie

Role: CONTACT

ouyangpy@sysucc.org.cn

020-87342926

Facility Contacts

Puyun Ouyang

Role: primary

ouyangpy@sysucc.org.cn

+8602087342926

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Other Identifiers

B2023-110-X02

Identifier Type: -

Identifier Source: org_study_id