GAPP Induction and Concurrent Chemoradiotherapy for High-risk Locoregionally Advanced NPC.

Official title

An Open-label, Multicenter, Randomized Controlled Phase III Clinical Trial of PD-1 Monoclonal Antibody Plus Anlotinib Combined With Induction and Concurrent Chemoradiotherapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma.

Overview

The investigators have designed a multicenter, open-label, randomized controlled phase III clinical study of GAPP induction therapy followed by concurrent chemoradiotherapy and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition). The aim is to obtain high-level, high-quality evidence-based data to clarify the efficacy and safety of combining chemoradiotherapy with PD-1 antibody and anlotinib, thereby providing a new treatment strategy to improve the prognosis of patients with high-risk locoregionally advanced nasopharyngeal carcinoma. In this study, GPP induction chemotherapy followed by concurrent chemoradiotherapy and toripalimab maintenance therapy is selected as the control group. This regimen is currently the standard treatment recommended by guidelines for high-risk locoregionally advanced nasopharyngeal carcinoma, with well-established efficacy and broad clinical application. It provides a reliable benchmark for comparing the efficacy and safety of the experimental group, meets ethical requirements, and has mature clinical operational procedures.

Detailed description

The investigators have designed a multicenter, open-label, randomized controlled phase III clinical study of GAPP (gemcitabine + anlotinib + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition). The aim is to obtain high-level, high-quality evidence-based data to clarify the efficacy and safety of combining chemoradiotherapy with PD-1 antibody and anlotinib, thereby providing a new treatment strategy to improve the prognosis of patients with high-risk locoregionally advanced nasopharyngeal carcinoma. In this study, GPP (gemcitabine + cisplatin + toripalimab) induction chemotherapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy is selected as the control group. This regimen is currently the standard treatment recommended by guidelines for high-risk locoregionally advanced nasopharyngeal carcinoma, with well-established efficacy and broad clinical application. It provides a reliable benchmark for comparing the efficacy and safety of the experimental group, meets ethical requirements, and has mature clinical operational procedures.

Interventions

• Drug Toripalimab
  Toripalimab, 240 mg per administration, on Day 1, diluted in 100 mL of normal saline, administered as an intravenous infusion over 30 minutes (no less than 20 minutes and no more than 60 minutes). After the toripalimab infusion, there should be an interval of 30-60 minutes before administering gemcitabine and cisplatin. Each treatment cycle is 21 days. If the subject's toxicity recovery does not meet the criteria for the next cycle of chemotherapy, the start of the next cycle may be appropriatel
• Drug Anlotinib
  Anlotinib, 8 mg per dose per day, once daily on Days 1-14, taken orally before breakfast. Each treatment cycle is 21 days. If the subject's toxicity recovery does not meet the criteria for the next cycle of chemotherapy, the start of the next cycle may be appropriately delayed, but the delay should not exceed 21 days. A total of 3 cycles will be administered.
• Drug Cisplatin
  Cisplatin, with a treatment cycle of 21 days. If the subject's toxicity recovery does not meet the criteria for the next cycle of chemotherapy, the start of the next cycle may be appropriately delayed, but the delay should not exceed 21 days. A total of 5 cycles will be administered.
• Drug Gemcitabine
  Gemcitabine, 1000 mg/m², on Days 1 and 8, diluted in 500 mL of 0.9% normal saline, administered as an intravenous infusion. Each treatment cycle is 21 days. If the subject's toxicity recovery does not meet the criteria for the next cycle of chemotherapy, the start of the next cycle may be appropriately delayed, but the delay should not exceed 21 days. A total of 3 cycles will be administered.
• Radiation radiation
  IMRT

Primary outcome measures

• 3-year progression-free survival [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.]

Eligibility criteria

Inclusion criteria

• Voluntary participation and signed informed consent.
• Age 18-65 years, male or non-pregnant female.
• Pathologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or III).
• Previously untreated patients with no history of other malignancies; initial treatment for nasopharyngeal carcinoma.
• Stage III: TanyN3M0 / T4N0-2M0 (9th AJCC/UICC staging system).
• ECOG performance status 0-1, with no severe dysfunction of vital organs (heart, lung, liver, kidney, etc.).
• Hemoglobin (HGB) ≥90 g/L, white blood cell count (WBC) ≥4.0×10\^9 /L, platelet count (PLT) ≥100×10\^9/L.
• Liver function: ALT and AST <2.5× upper limit of normal (ULN); total bilirubin <2.0×ULN.
• Renal function: serum creatinine <1.5×ULN.

Exclusion criteria

• Patients with recurrent or distant metastatic nasopharyngeal carcinoma.
• Pathologically confirmed keratinizing squamous cell carcinoma (WHO type I).
• Receipt of systemic or topical glucocorticoid therapy within 4 weeks prior to enrollment.
• Participation in another clinical trial of an investigational drug within 3 months prior to treatment.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Patients with idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans), radiation pneumonitis that is clinically symptomatic or requires steroid therapy, active pneumonitis, or other moderate-to-severe pulmonary diseases that significantly affect lung function.
• Comorbidities requiring long-term immunosuppressive medication or systemic/topical corticosteroids at immunosuppressive doses.
• Prior use of anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies (or any other antibodies targeting T-cell co-stimulatory or checkpoint pathways) with documented disease progression at the time of study entry.
• Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis). Patients with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be included; patients requiring bronchodilators for medical management of asthma are excluded.
• HIV-positive; HBsAg-positive with detectable HBV DNA copy number (quantitative detection ≥1000 cps/mL); positive hepatitis C antibody (HCV Ab) with detectable HCV RNA.
• Receipt of any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine) within 4 weeks prior to enrollment.
• Positive pregnancy test in women of childbearing potential, or lactating women.
• Inability to comply with scheduled follow-up due to psychological, social, family, or geographical reasons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun yat-sen university cancer center — Guangzhou

Identifiers

NCT: NCT07540390 · 2025-FXY-482-NPC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗