EP-STAREpstein-Barr Virus DNA to Systemic Therapy for Treatment Adaptation in High Risk Nasopharyngeal Carcinoma (EP-STAR Trial) A Phase II, Multi-center, Biomarker-guided, Umbrella Trial
sintilimab
+ Capecitabine
Nasopharyngeal Carcinoma+11
+ Carcinoma
+ Head and Neck Neoplasms
Treatment Study
Summary
Study start date: June 1, 2020
Actual date on which the first participant was enrolled.Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer characterized by an extremely unbalanced global distribution. The highest incidence is observed in endemic regions, such as southern China and Southeast Asia, with an age-standardized rate of 3.0 per 100,000 in China to 0.4 per 100,000 in Caucasian populations. The fast progress of modern imaging and the application of intensity-modulated radiotherapy (IMRT) has improved the local control rate significantly. Distant metastasis has become the major cause of treatment failure. The 2018 National Comprehensive Cancer Network (NCCN) guideline recommends concurrent chemoradiotherapy (CCRT) ± induction chemotherapy (IC)/adjuvant chemotherapy (AC) as the standard treatment for stage II-IVa disease (category 2A). While it is worth noting that there is extensive heterogeneity among patients with NPC, and even among patients with the same disease stage, the risk of relapse varies. More importantly, patients can have differing sensitivity to RT and chemotherapy. The abovementioned reasons result in over-treatment in some patients with relatively low relapse risk; intensive treatments lead to unnecessary toxicities, and greatly affect quality of life (QoL). On the other hand, the current treatment strategy may be not optimal for patients with high relapse risk or who are not sensitive to traditional chemoradiotherapy. Therefore, there is an urgent need for identifying and applying promising biomarkers, real-time monitoring of patient responses to treatment, predicting relapse risk, and guiding real-time treatment adaptation for individualized therapy. The investigators aim to investigate whether incorporating on-treatment EBV DNA surveillance for monitoring tumor responses to treatment and for guiding individuliased treatment adaptation can improve prognosis in nasopharyngeal carcinoma patient . For patients with detectable EBV DNA after one cycle of IC, which then drops to undetectable levels during the following IC cycles (intermediate responders/intermediate relapse risk), the investigators aim to investigate whether additional adjuvant metronomic capecitabine would benefit this subgroup. For patients with detectable EBV DNA after three cycles of IC or with EBV DNA bounce during the induction phase (insensitive to IC/high relapse risk), the investigators aim to investigate whether concurrent administration of anti-PD-1 therapy during the following treatment phases (including concurrent phase and adjuvant phase) can benefit this subgroup.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.110 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 65 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: 1. Newly diagnosed, pathologically proven World Health Organization (WHO) type II/III untreated LANPC; 2. LANPC (except T3N0, according to the 8th edition of the AJCC/UICC clinical staging system); 3. Age at diagnosis: 18-65 years; 4. Eastern Cooperative Oncology Group (ECOG) score: 0-1 5. Receiving recommended three cycles of induction chemotherapy (IC) (gemcitabine-cisplatin \[GP\] regimen); 6. Pre-treatment and post-IC1 cell-free Epstein-Barr virus (cfEBV) DNA \> 0 copy/mL; systemic cfEBV DNA monitoring during IC phase for risk stratification; 7. Normal hematic, liver, and kidney function: hemoglobin (HG) \> 90 g/L; neutrophil \> 1.5 × 109/L; platelet \> 100 × 109/L; total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 × ULN; alkaline phosphatase (ALP) ≤ 2.5 × ULN; creatinine clearance (Ccr) ≥ 60 mL/min; 8. Female subjects capable of becoming pregnant agree to use reliable contraceptive measures from screening to 1 year after treatment; 9. Patients will be required to sign informed consent forms and be willing and able to comply with the requirements for visits, treatment, laboratory tests, and other research requirements stipulated in the research schedule. Exclusion Criteria: 1. Receiving surgery, target therapy, and/or immunotherapy during or before induction phase; 2. Hepatitis B surface antigen-positive \[HBsAg(+)\],hepatitis B virus (HBV) DNA \> 1×103 copy/mL; hepatitis C virus (HCV) antibody(+); 3. Other previous or concurrent malignant tumors, except adequately treated non-melanoma skin cancer, cervical carcinoma in situ, and thyroid papillary cancer; 4. Pregnant or lactating women (a pregnancy test should be considered for fertile women with an active sex life); 5. Previously treated with radical radiotherapy (RT), except non-melanoma skin cancers outside intended RT treatment volume; 6. Uncontrolled heart disease, e.g.: 1) Heart failure, Hew York Heart Association (NYHA) level ≥ 2; 2) unstable angina; 3) myocardial infarction in the past 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention; \*For patients recruited to Arm II, the additional exclusion criteria are: 7. Active, known, or suspected autoimmune disease (including, but not limited to, uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism, and asthma requiring bronchiectasis). Exceptions are type I diabetes mellitus, hypothyroidism requiring hormone replacement therapy, and skin disorders requiring no systemic treatment (e.g., vitiligo, psoriasis, alopecia); 8. Received live vaccine within 1 month before treatment initiation; 9. Allergy to macromolecular protein preparations, or any component of sintilimab; 10. Human immunodeficiency virus (HIV)-positive or diagnosed with Acquired Immune Deficiency Syndrome (AIDS).
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.2 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Sun Yat-sen University Cancer Center
Guangzhou, ChinaOpen Sun Yat-sen University Cancer Center in Google Maps