LDRT Combined With Toripalimab and Chemotherapy for Recurrent/Metastatic NPC

Официальное название

Low-dose Radiotherapy (LDRT) Combined With Toripalimab and GP Chemotherapy for Recurrent/Metastatic Nasopharyngeal Carcinoma (LIGHT): A Multicentre, Open-Label, Single-Arm Phase II Clinical Study

Обзор

This study aims to evaluate the efficacy and safety of LDRT combined with toripalimab and GP chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma through a prospective, open-label, single-arm Phase II clinical trial.

Вмешательства

• Препарат Gemcitabine(GEM)
  Gemcitabine 1000mg/m2, d1 \& 8 of every cycle, every 3 weeks for 4-6 cycles
• Препарат Cisplatin
  Cisplatin 80mg/m2, d1 of every cycle, every 3 weeks for 4-6 cycles
• Препарат Toripalimab
  Toripalimab 240 mg, d1of every cycle, every 3 weeks for 4-6 cycles. Toripalimab maintenance, 240 mg, d1of every cycle, every 3 weeks until disease progression or unacceptable toxicity.
• Лучевая терапия LDRT
  Irradiation of the primary lesion and regional metastatic lymph nodes, 0.5 Gy per fraction for 4 fractions, d0-3, every 3 weeks for 4-6 cycles

Первичные конечные точки

• Progression-free survival (PFS) assessed by RECIST 1.1 [Срок оценки: up to approximately 2 years]

Вторичные конечные точки (4)

• Objective Response Rate（ORR） [Срок оценки: up to approximately 2 years]
• Progression-free survival (PFS) assessed by iRECIST [Срок оценки: up to approximately 2 years]
• Overall survival (OS) [Срок оценки: up to approximately 4 years]
• Adverse events [Срок оценки: up to approximately 2 years]

Критерии участия

Критерии включения

• Age: 18-65 years old.
• Histologically confirmed non-keratinizing nasopharyngeal carcinoma (WHO Type II or III).
• ECOG Performance Status score of 0-1.
• At least one measurable lesion as per RECIST v1.1 criteria.
• Patients with newly diagnosed metastatic NPC, or patients with locoregionally advanced NPC who developed metastasis ≥6 months or recurrence ≥12 months after completing radical radiotherapy/chemotherapy for the primary lesion.
• No prior radiotherapy, chemotherapy, immunotherapy, or biological therapy for recurrent/metastatic lesions.
• Adequate organ function, meeting the following criteria within 7 days prior to treatment:

• Hematological criteria (without transfusion or hematopoietic growth factor support within 14 days):

• Hemoglobin (Hb) ≥90 g/L.
• White Blood Cell (WBC) count ≥4.0 × 10⁹/L.
• Platelet count (PLT) ≥100 × 10⁹/L.
• Biochemical criteria:

• Total Bilirubin (TBIL) ≤1.5 × Upper Limit of Normal (ULN).
• Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5 × ULN.
• Serum Creatinine (Cr) ≤1.5 × ULN AND Creatinine Clearance (CCr) ≥60 mL/min.
• Coagulation function: INR and APTT ≤1.5 × ULN.
• Normal results for myocardial injury markers, heart failure markers, and electrocardiogram (ECG). For patients with abnormal results in any of these, the investigator will assess the need for Doppler echocardiography.
• Thyroid function: TSH ≤ ULN. If abnormal, FT3 and FT4 levels should be considered; patients can be enrolled if FT3 and FT4 levels are normal.
• Women of childbearing potential must have used reliable contraception, have a negative serum pregnancy test within 7 days before enrollment, and be willing to use adequate contraception during the trial and for 8 weeks after the last dose of the study drug, or be surgically sterile. Men must agree to use adequate contraception or be surgically sterile during the trial and for 8 weeks after the last dose.
• Voluntary provision of signed informed consent, with good compliance.

Критерии исключения

• Disease progression within 6 months after completing standard treatment for locoregionally advanced nasopharyngeal carcinoma.
• Absence of identifiable tumor lesions in both the primary site and locoregional lymph nodes, precluding the development of an LDRT plan.
• Inability to undergo MRI due to reasons such as implanted metal devices or claustrophobia.
• Requirement for systemic use of corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose or during the study. Inhaled or topical steroids and adrenal replacement steroid doses >10 mg/day prednisone equivalent are permitted in the absence of active autoimmune disease. Physiological replacement doses of corticosteroids (≤10 mg/day prednisone equivalent) are allowed.
• Recurrent target lesions suitable for curative surgery or a second course of radiotherapy.
• History of any active autoimmune or autoimmune disease, or known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. Exceptions include type I diabetes, hypothyroidism requiring hormone replacement therapy, and skin disorders not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
• Active or uncontrolled severe infection (≥CTCAE Grade 3) within 4 weeks prior to enrollment.
• History of active tuberculosis within the past year, regardless of treatment. Patients with a history of active pulmonary tuberculosis over 1 year ago who have documented evidence of adequate past anti-tuberculosis treatment may be considered; otherwise, they are excluded.
• History of hypertension that cannot be adequately controlled with a single antihypertensive medication (systolic BP ≥150 mmHg or diastolic BP ≥90 mmHg).
• Clinically significant bleeding symptoms or definite bleeding tendency, specifically excluding cases of local recurrence with high bleeding risk or cases within 1 year post-radiotherapy assessed to have a high risk of necrosis.
• Urinalysis showing urine protein ≥ ++ AND confirmed 24-hour urine protein ≥1.0 g.
• Myocardial ischemia (above Grade I), myocardial infarction, arrhythmia (including QTc ≥480 ms), or ≥ Grade 2 congestive heart failure (NYHA classification) within 6 months prior to enrollment.
• If an echocardiogram is required per Inclusion Criterion 7(4), results showing Left Ventricular Ejection Fraction (LVEF) below the lower limit of normal (60%).
• Diagnosis of other malignancies within 5 years prior to enrollment, except for cured non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma.
• Presence of leptomeningeal or central nervous system metastases.
• HIV positive, TP positive, liver cirrhosis, decompensated liver disease, active hepatitis (uncontrolled active hepatitis despite treatment: Hepatitis B - HBsAg positive and HBV DNA ≥1 × 10⁴ copies/mL; Hepatitis C - HCV RNA positive with abnormal liver function; co-infection with HBV and HCV) requiring antiviral therapy.
• Participation in another anti-tumor drug clinical trial within 4 weeks prior to enrollment.
• Administration of any live attenuated vaccine within 30 days prior to enrollment.
• Contraindications to radiotherapy.
• Known allergy to the study drug or any of its excipients, or history of severe allergic reactions to other monoclonal antibodies.
• History of psychoactive drug abuse unable to be abstained, or presence of psychiatric disorders.
• Any other condition assessed by the investigator as potentially endangering the patient's safety or compliance, including severe concurrent diseases (including psychiatric disorders) requiring prompt treatment, severely abnormal laboratory test results, or other psychological, familial, or sociological factors deemed high-risk.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Sun Yat-sen University Cancer Center — Гуанчжоу
• Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Unio — Шэньчжэнь

Публикации

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• Herrera FG, Ronet C, Ochoa de Olza M, Barras D, Crespo I, Andreatta M, Corria-Osorio J, Spill A, Benedetti F, Genolet R, Orcurto A, Imbimbo M, Ghisoni E, Navarro Rodrigo B, Berthold DR, Sarivalasis A, Zaman K, Duran R, Dromain C, Prior J, Schaefer N, Bourhis J, Dimopoulou G, Tsourti Z, Messemaker M, Smith T, Warren SE, Foukas P, Rusakiewicz S, Pittet MJ, Zimmermann S, Sempoux C, Dafni U, Harari A, PMID 34479871
• Zhou L, Liu Y, Wu Y, Yang X, Spring Kong FM, Lu Y, Xue J. Low-dose radiation therapy mobilizes antitumor immunity: New findings and future perspectives. Int J Cancer. 2024 Apr 1;154(7):1143-1157. doi: 10.1002/ijc.34801. Epub 2023 Dec 7. PMID 38059788

Идентификаторы

NCT: NCT07325539 · 2025-FXY-451-FLK

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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