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

Nasopharyngeal Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06313450
• Other study ID #: B2023-110-X02
• Status: Recruiting
• Phase: N/A
• Start date: March 4, 2024
• Est. completion date: February 1, 2028

Study information

• Verified date: March 2024
• Source: Sun Yat-sen University
• Contact: Puyun Ouyang
• Phone: +8602087342926
• Email: ouyangpy[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: February 1, 2028
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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;

Related Conditions & MeSH terms

• Carcinoma
• IMMUNOTHERAPY
• Nasopharyngeal Carcinoma
• Radiotherapy; Complications

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (9)

Chen AM, Felix C, Wang PC, Hsu S, Basehart V, Garst J, Beron P, Wong D, Rosove MH, Rao S, Melanson H, Kim E, Palmer D, Qi L, Kelly K, Steinberg ML, Kupelian PA, Daly ME. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma — View Citation

Liu YP, Wen YH, Tang J, Wei Y, You R, Zhu XL, Li J, Chen L, Ling L, Zhang N, Zou X, Hua YJ, Chen YM, Chen L, Lu LX, Chen MY, Wen WP. Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma — View Citation

Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, Westra WH, Gilbert J, Bauman JE, Wagner LI, Trevarthen DR, Balkrishna J, Murphy BA, Agrawal N, Colevas AD, Chung CH, Burtness B. E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced — View Citation

OuYang PY, Zhang BY, Guo JG, Liu JN, Li J, Peng QH, Yang SS, He Y, Liu ZQ, Zhao YN, Li A, Wu YS, Hu XF, Chen C, Han F, You KY, Xie FY. Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal — View Citation

Peng H, Chen L, Zhang Y, Li WF, Mao YP, Liu X, Zhang F, Guo R, Liu LZ, Tian L, Lin AH, Sun Y, Ma J. The Tumour Response to Induction Chemotherapy has Prognostic Value for Long-Term Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasophary — View Citation

Tang LL, Guo R, Zhang N, Deng B, Chen L, Cheng ZB, Huang J, Hu WH, Huang SH, Luo WJ, Liang JH, Zheng YM, Zhang F, Mao YP, Li WF, Zhou GQ, Liu X, Chen YP, Xu C, Lin L, Liu Q, Du XJ, Zhang Y, Sun Y, Ma J. Effect of Radiotherapy Alone vs Radiotherapy With Co — View Citation

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Yao JJ, Jin YN, Lin YJ, Zhang WJ, Marks T, Ryan I, Zhang HY, Xia LP. The feasibility of reduced-dose radiotherapy in childhood nasopharyngeal carcinoma with favorable response to neoadjuvant chemotherapy. Radiother Oncol. 2023 Jan;178:109414. doi: 10.1016 — View Citation

Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	local recurrence rate(LRR)	Defined as the proportion of patients with local recurrence within 3 years	3 years
Secondary	primary tumor volume regression=75% rate		Two weeks after the third cycle of neoadjuvant immunochemotherapy (each cycle is 21 days), prior to radiotherapy
Secondary	3-year overall survival		3 years
Secondary	acute and late radiation-induced toxicities		up to 3 years after radiotherapy, respectively
Secondary	complete response rate of primary tumor		Two weeks after the third cycle of neoadjuvant immunochemotherapy (each cycle is 21 days) and six months after radiotherapy.