PD-1 Monoclonal Antibody Combined With Gemcitabine and Cisplatin Followed by Selective Radiotherapy for Unresectable Locally Recurrent Nasopharyngeal Carcinoma: A Multicenter, Prospective, Single-Arm Phase II Trial
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 86
- Primary Endpoint
- Overall survival
Overview
Brief Summary
The investigators plan to conduct a multicenter, prospective, single-arm phase II clinical trial of PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy for unresectable locally recurrent nasopharyngeal carcinoma to evaluate the efficacy and safety of PD-1 antibody plus GP chemotherapy followed by sequential selective radiotherapy in patients with unresectable locally recurrent disease who achieve tumor regression after immunochemotherapy, thereby providing evidence-based medical evidence for the treatment of unresectable locally recurrent NPC and improving treatment outcomes for these patients.
Detailed Description
The addition of immunotherapy plays an important role in disease control for recurrent/metastatic nasopharyngeal carcinoma (NPC) and has become an indispensable part of NPC treatment. However, current studies on recurrent/metastatic NPC have enrolled patients with both locally recurrent and metastatic disease, and most patients with recurrence also have distant metastasis, with locally recurrent NPC patients accounting for a very small proportion (JUPITER-02: 13%; CAPTAIN-1st: 0; RATIONALE-309: 3.8%). Due to the high heterogeneity of recurrent/metastatic NPC, patient prognoses vary greatly, and treatment regimens for locally recurrent NPC remain lacking standardization. The investigators plan to conduct a multicenter, prospective, single-arm phase II clinical trial of PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy for unresectable locally recurrent nasopharyngeal carcinoma to evaluate the efficacy and safety of PD-1 antibody plus GP chemotherapy followed by sequential selective radiotherapy in patients with unresectable locally recurrent disease who achieve tumor regression after immunochemotherapy, thereby providing evidence-based medical evidence for the treatment of unresectable locally recurrent NPC and improving treatment outcomes for these patients.
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Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18-70 years, any gender.
- •Local recurrence (with or without regional recurrence) more than one year after radical treatment and unsuitable for surgery.
- •Pathologically confirmed non-keratinizing nasopharyngeal carcinoma (WHO type II or III).
- •Achieved complete response (CR) or partial response (PR) after 4-6 cycles of chemotherapy plus PD-1 inhibitor therapy.
- •ECOG performance status 0-
- •Expected survival ≥ 3 months.
- •No prior radiotherapy, chemotherapy, immunotherapy, or biological therapy for recurrent nasopharyngeal carcinoma
- •No contraindications to immunotherapy, chemotherapy, or re-irradiation.
- •Adequate organ function within 14 days before first dose, defined as:
- •Hematology：Hemoglobin ≥ 90 g/L，ANC ≥ 1.5 × 10⁹/L，Platelet count ≥ 100 × 10⁹/L Renal Function：Creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) / eGFR ≥ 60 mL/min Liver Function：Total bilirubin ≤ 1.5 × ULN，AST and ALT ≤ 2.5 × ULN, or ≤ 5 × ULN in the presence of liver metastases
Exclusion Criteria
- •Presence of grade 3 or higher late radiation toxicity (excluding skin, subcutaneous tissue, and mucosa) at the time of recurrence
- •Prior anti-tumor therapy for recurrent nasopharyngeal carcinoma, including radiotherapy, chemotherapy, surgery, or immunotherapy.
- •Prior treatment with PD-1/PD-L1 or CTLA-4 inhibitors.
- •History of other malignancies within the past 5 years, except adequately treated basal cell carcinoma, squamous cell skin cancer, or in-situ cervical cancer.
- •Active autoimmune disease or history of autoimmune disease requiring systemic treatment (e.g., corticosteroids, immunosuppressants) within the past 2 years, except for stable hypothyroidism, type 1 diabetes mellitus, or resolved childhood asthma/atopy.
- •Known history of active pulmonary tuberculosis (TB). Suspected active TB must be excluded by chest X-ray, sputum examination, and assessment of clinical signs and symptoms.
- •Hepatitis B: HBsAg positive with peripheral blood HBV DNA ≥ 1000 copies/mL
- •Hepatitis C: HCV antibody positive, eligible only if HCV RNA is negative
- •HIV infection
- •Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within 6 months, congestive heart failure ≥ NYHA class II, or serious arrhythmia).
Arms & Interventions
Selective re-irradiation group
Intervention: PD-1 monoclonal antibody combined with gemcitabine and cisplatin followed by selective radiotherapy (Drug)
Outcomes
Primary Outcomes
Overall survival
Time Frame: 3 years
the time from the date of treatment initiation to the date of death due to any cause.
Secondary Outcomes
- Progression free-survival(3 years)
- Locoregional progression-free survival(3 years)
- Distant progression-free survival(3 years)
- Incidence of toxicity(3 years)
- Quality of life (QoL)(3 years)
Investigators
Hai-Qiang Mai,MD,PhD
Principal Investigator
Sun Yat-sen University