Adebrelimab and Chemoradiotherapy in High-risk LANPC

Phase 2

Recruiting

• Conditions: Nasopharyngeal Cancer; Nasopharyngeal Carcinoma
• Interventions: Drug: Adebrelimab

• Registration Number: NCT06349889
• Lead Sponsor: Sun Yat-sen University

Brief Summary

This trial aims to study the role of Adebrelimab combined with induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) for high-risk locoregionally advanced nasopharyngeal carcinoma(LANPC).

Detailed Description

The trial plans to enroll patients with stage IVA+T3N2M0 (AJCC 8th) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation plus Adebrelimab in induction chemotherapy and adjuvant chemotherapy. Adebrelimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 3 cycles in induction therapy and for 9 cycles in adjuvant therapy.

Study Timeline

• Study First Submitted: 2024-03-31
• Study First Submitted QC: 2024-03-31
• Study First Posted: 2024-04-05
• Study Start: 2024-07-23
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-13
• Last Update Posted: 2025-01-15
• Primary Completion: 2028-05-01
• Study Completion: 2028-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Patients with histologically confirmed nasopharyngeal carcinoma.
2. Tumor staged as IVA+T3N2M0 (AJCC 8th).
3. Eastern Cooperative Oncology Group performance status ≤1.
4. Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
5. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
6. Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
7. Patients must be informed of the investigational nature of this study and give written informed consent.
8. Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug

Exclusion Criteria

1. Age > 65 or < 18.
2. Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 copies/ml or 200IU/ml
3. Hepatitis C virus (HCV) antibody positive
4. Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
5. Has any condition that required systemic corticosteroid (equivalent to prednisone >10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed.
6. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed.
7. Has a known history of interstitial lung disease.
8. Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
9. Is pregnant or breastfeeding.
10. Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
11. Has known allergy to large molecule protein products or any compound of Adebrelimab.
12. Has a known history of human immunodeficiency virus (HIV) infection.
13. Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adebrelimab arm	Adebrelimab	Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Adebrelimab 1200mg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 9 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.

Primary Outcome Measures

Name	Time	Method
Failure-free survival (FFS)	3 years	calculated from enrolment to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	3 years	calculated from enrolment to the date of death from any cause.
Quality of life (QoL)	3 years	The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 13-16 weeks after radiotherapy, 2 years and 3 years after randomization. The EORTC QoL questionnaire-C30 (EORTC QLQ-C30）version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual.
Distant metastasis-free survival (DMFS)	3 years	calculated from enrolment to the date of first distant metastasis.
Locoregional recurrence-free survival (LRRFS)	3 years	calculated from enrolment to the date of locoregional persistence or 1st locoregional recurrence.
Adverse events (AEs) and serious adverse events (SAEs)	3 years	Graded according to CTCAE V5.0.
Failure-free survival (FFS) within different subgroups	3 years	analyses for FFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (≤4000copies/ml vs. \>4000copies/ml), different Programmed Death-1（PD-L1） expression levels, age, gender, performance status, T category, N category, and stage (III vs. IVA).

Trial Locations

Locations (4)

The First Affiliated Hospital of Xiamen University; 🇨🇳 Xiamen, Fujian, China

Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China