Short-course Tislelizumab Combined With Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized, Controlled, Multicenter, Phase 3 Non-inferiority Clinical Trial
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 418
- Primary Endpoint
- Failure-free survival (FFS)
Overview
Brief Summary
This trial aim to explore whether short-course tislelizumab (3 cycles of 200 mg q3w in the induction phase and 3 cycles of 400 mg q6w in the consolidation phase) yields non-inferior event-free survival compared to long-course tislelizumab (3 cycles of 200 mg q3w in the induction phase and 5 cycles of 400 mg q6w in the consolidation phase) in patients with locoregionally advanced nasopharyngeal carcinoma.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥18 and ≤65 years
- •Patients with histologically confirmed non-keratinizing nasopharyngeal carcinoma according to WHO criteria.
- •Eastern Cooperative Oncology Group performance score of 0-
- •Tumor staged as T4N1 and T1-4N2-3 disease (AJCC 9th edition).
- •Adequate marrow function:
- •white blood cell count \> 4 × 10⁹/L hemoglobin \>90g/L and platelet count \>100×10⁹/L
- •Adequate hepatic and renal function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN), Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×ULN, Alkaline phosphatase ≤ 2.5 ×ULN, clearance rate ≥ 60 ml/min
- •Other laboratory and clinical criteria Normal: thyroid function, serum amylase and lipase, pituitary hormone levels, inflammatory markers, cardiac enzyme tests and electrocardiogram (ECG); For patients aged \>50 years with a history of smoking, normal pulmonary function test (PFT) results are required; For patients with abnormal ECG findings or a prior history of cardiovascular disease (not meeting any
Exclusion Criteria
- •listed in Item 8), additional assessments including myocardial function evaluation and cardiac ultrasound (echocardiography) must be performed, with results within normal limits.
- •8\. Patients must be informed of the investigational nature of this study and give written informed consent, and be willing and able to comply with the study schedule, including follow-up visits, treatment procedures, laboratory testing, and other protocol-related requirements.
- •9\. Women of childbearing potential (WOCBP) must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug.
- •Exclusion Criteria:
- •Positive for hepatitis B surface antigen (HBsAg) with hepatitis B virus DNA \>1×10 copies/mL, positive for anti-hepatitis C virus (HCV) antibody, positive for anti-hepatitis C virus (HCV) antibody
- •Positive for anti-HIV antibody or diagnosed with acquired immunodeficiency syndrome (AIDS).
- •Active pulmonary tuberculosis: Patients with a history of active tuberculosis within the past year should be excluded regardless of treatment status. Patients with a history of active pulmonary tuberculosis more than one year prior should also be excluded, unless they received con dirmed and regular anti-tuberculosis treatment.
- •Active, known, or suspected autoimmune diseases, including but not limited to uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, systemic lupus erythematosus, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators. Type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) are allowed.
- •History of interstitial lung disease or pneumonia requiring oral or intravenous corticosteroids within the past year; use of vancomycin within the past month.
- •Ongoing chronic systemic corticosteroid therapy (equivalent to or greater than prednisone \>10mg per day) or any other immunosuppressive therapy. Patients received inhale or topical corticosteroid are allowed.
Arms & Interventions
tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.
Intervention: tislelizumab (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.
Intervention: Gemcitabine + cisplatin (GP) (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.
Intervention: Cisplatin (100mg/m2) (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 3×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 3 cycles.
Intervention: intensity-modulated radiotherapy (Radiation)
tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.
Intervention: tislelizumab (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.
Intervention: Gemcitabine + cisplatin (GP) (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.
Intervention: Cisplatin (100mg/m2) (Drug)
tislelizumab (3×200 mg q3w neoadjuvant + 5×400 mg q6w adjuvant)
Patients will receive neoadjuvant gemcitabine (1000 mg/m2 d1, d8), cisplatin (80 mg/m2 d1) and tislelizumab (200 mg) every 3 weeks for 3 cycles, followed by defnitive intensitymodulated radiotherapy (IMRT) of 6996cGy in 33 fractions. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Subsequently, adjuvant therapy with tislelizumab (400 mg) every 6 weeks for 5 cycles.
Intervention: intensity-modulated radiotherapy (Radiation)
Outcomes
Primary Outcomes
Failure-free survival (FFS)
Time Frame: 3 years
From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.
Secondary Outcomes
- Overall survival (OS)(3 years)
- Distant metastasis-free survival (DMFS)(3 years)
- Locoregional recurrence-free survival (LRRFS)(3 years)
- Adverse events (AEs)(within 5 years)
- Quality of life (QoL)(week 0, 9, 16, 28, 40 and 1 year, 2 years, 3 years, 4 years, and 5 years after randomization)
- cost-effectiveness analysis(3 years)
Investigators
Jun Ma, MD
Professor
Sun Yat-sen University