Nasopharyngeal Carcinoma
Conditions
Keywords
Nasopharyngeal Carcinoma, Immune checkpoint inhibitor, Radiotherapy, Concurrent cisplatin
Brief summary
This is a phase 3, multi-center, randomized controlled trial, with the purpose to evaluate the therapeutic efficacy and safety of PD-1 blockade (toripalimab) combined with the de-intensified chemoradiotherapy sparing concurrent cisplatin (i.e., toripalimab incorporated into induction chemotherapy and radiotherapy) in high-risk locoregionally advanced nasopharyngeal carcinoma.
Detailed description
This phase 3, multi-center, randomized controlled trial plans to enroll 532 patients with newly-diagnosed, pathologically-proven, untreated locoregionally advanced nasopharyngeal carcinoma (LANPC) at high-risk of distant metastasis (T4N1 and T1-4N2-3, according to American Joint Committee on Cancer \[AJCC\]/Union for International Cancer Control \[UICC\] 8th edition clinical staging system). Patients will receive 3 cycles of induction chemotherapy (IC; gemcitabine-cisplatin regimen) followed by 1) experimental arm (de-intensification group): intensity-modulated radiotherapy (IMRT) alone or 2) control arm (standard group): 2 cycles of concurrent cisplatin plus IMRT (CCRT). For both of the two arms, toripalimab will be adopted on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, with the first and last 3 cycles of toripalimab administrated along with IC and CCRT/IMRT, respectively. After three weeks of the completion of IMRT, adjuvant toripalimab will be used every 3 weeks for 11 cycles, and therefore the entire treatment process is expected to last for one year.
Interventions
1. IC phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 240 mg, day 1; start on day 1 of the first cycle IC and continue every 3 weeks for 3 cycles till the end of IC. 2. IMRT phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 240 mg, day 1; start on day 1 of IMRT or CCRT and continue every 3 weeks for 3 cycles till the end of IMRT. 3. Adjuvant PD-1 blocking antibody: every 3 weeks × 11 cycles; 240 mg, day 1
DRUGGemcitabine
Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles
DRUGCisplatin (80mg/m2)
Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles
Cisplatin as concurrent chemotherapy, 100 mg/m2 day 1 per cycle, every 3 weeks for 2 cycles
RADIATIONIntensity-modulated radiotherapy
Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18 to 65; 2. Pathological type: non-keratinizing carcinoma (World Health Organization criteria); 3. Diagnosed with LANPC (T4N1, T1-4N2-3) according to the 8th edition clinical staging system of the American Joint Committee on Cancer \[AJCC\]/Union for International Cancer Control \[UICC\]; 4. ECOG performance score: 0 to 1; 5. Normal bone marrow function: white blood cell count \> 4×109/L, hemoglobin \> 90g/L, platelet count \> 100×109/L; 6. Normal values of thyroid function, amylase and lipase examination, pituitary function, inflammation and infection indicators, myocardial enzymes, and ECG results. For patients older than 50 years with a smoking history, normal lung function are required. Patients with abnormal ECG and/or a history of vascular disease (but not meeting the
Exclusion criteria
listed in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Failure-free survival (FFS) | 3-year | Failure-free survival is measured from day of diagnosis until treatment failure, death from any cause, or last follow-up visit, whichever occurred first |
| Incidence rate of all-grade vomiting | Through study completion, an average of 1 year | Incidence rate of all-grade vomiting during treatment assessed by clinicians according to the Common Terminology Criteria for Adverse Events 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant failure-free survival (DFFS) | 3-year | Distant failure-free survival is measured from day of diagnosis until distant metastasis |
| Incidence rate of investigator-reported adverse events (AEs) | 3-year | Analysis of investigator-reported adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0 |
| Overall survival (OS) | 3-year | Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive |
| Quality of life (QoL): questionnaire | week 1, 20, 40, 64 | Changes in QoL of participants from initial treatment to 6 months after the completion of 6 cycles adjuvant PD-1 blocking antibody. QoL is evaluated with the use of (1) the head-and-neck-specific module (H&N35) of the Quality of Life Questionnaire-Core 30 module (QLQ-C30), which is established by European Organization for Research and Treatment of Cancer (EORTC) and (2) the general and head-and-neck-specific module of the evaluation tool developed by the Functional Assessment of Cancer Therapy (FACT). Scores for the module range of H&N35 QLQ-C30 from 0 to 100, with higher scores indicating better functioning or well-being or higher symptom burden (scales measuring symptom burden were reverse-scored to facilitate presentation) |
| Tumor response | Through study completion, an average of 1 year | Evaluation of tumor response (CR, PR, SD, PD, NA) performed after induction chemotherapy, radiotherapy, and adjuvant PD-1 immunotherapy. |
| Incidence rate of patient-reported adverse events (AEs) | 3-year | Analysis of patient-reported adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by patients themselves |
| Locoregional failure-free survival (LRFFS) | 3-year | Locoregional failure-free survival is measured from day of diagnosis until local or regional recurrence |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation between pre-treatment PD-L1 expression level and FFS | 3-year | Pre-treatment PD-L1 expression level of tumor cell is evaluated centrally by means of immunohistochemical testing. This is a single assessment with only one unit of measure, since the correlation is aimed to be roughly categorized into positive and negative. |
| Failure-free survival 2 (FFS 2) | within 10 years | The time from randomization to the second or subsequent disease progression after the initiation of new anticancer therapy, or death from any cause, whichever occurred first. |
| Correlation between pre-treatment PD-L1 expression level and OS | 3-year | Pre-treatment PD-L1 expression level of tumor cell is evaluated centrally by means of immunohistochemical testing. This is a single assessment with only one unit of measure, since the correlation is aimed to be roughly categorized into positive and negative. |
| Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS | 3-year | TILs are lymphoid cells (T cells) that infiltrate solid tumors (intra-tumoral TILs) and stroma (stromal TILs), which play an important role in the tumor microenvironment. This is a single assessment with only one unit of measure, since the correlation is aimed to be roughly categorized into positive and negative. |
| Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and OS | 3-year | TILs are lymphoid cells (T cells) that infiltrate solid tumors (intra-tumoral TILs) and stroma (stromal TILs), which play an important role in the tumor microenvironment. This is a single assessment with only one unit of measure, since the correlation is aimed to be roughly categorized into positive and negative. |
| Evaluate failure-free survival in the subgroup of age at diagnosis (year) | 3-year | Subgroup analysis |
| Evaluate failure-free survival in the subgroup of gender (male and female) | 3-year | Subgroup analysis |
| Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level | 3-year | Subgroup analysis |
| Evaluate failure-free survival in the subgroup of clinical stage | 3-year | Subgroup analysis |
| Evaluate the regression of tumor and parotid glands during radiotherapy | From the first fraction of radiotherapy to the end of treatment | Evaluate the anatomical (size, volume, and 3-dimensional axis) and dosimetric changes of primary tumor, lymph node, and parotid glands during 33-fractionation radiotherapy by using cone beam computed tomography |
Countries
China
Outcome results
None listed