EPstein-barr Virus DNA Response to Systemic Therapy for Treatment Adaptation in High Risk NPC (EP-STAR)

NCT04072107 | Unknown Phase 2

• 1 other identifier: B2019-185-01
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nasopharyngeal Carcinoma

Keywords

nasopharyngeal carcinoma; EBV DNA; Biomarker-guided; Treatment adaptation

Outcome Measures

Primary Outcomes (1)

• Failure-free survival

  FFS will be measured from the day of enrollment until treatment failure, death from any cause, or the last follow-up visit, whichever occurred first.

  2 year

Secondary Outcomes (6)

• overall survival

  2 year

• Distant metastasis failure-free survival

  2 year

• Locoregional failure-free survival

  2 year

• Adverse events

  up to 5 years

• Patient reported quality-of-life score

  up to 2 years

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive GP IC + IMRT concurrent with cisplatin chemotherapy + capecitabine AC. All patients will receive concurrent cisplatin (100 mg/m2) every 3 weeks, in a total of three cycles. All patients will receive low-dose metronomic capecitabine (650 mg/m2 bid, oral, d1-21, q3w) until disease progression, or intolerable toxicity or 6 months.

Drug: Capecitabine

Arm II

EXPERIMENTAL

Patients receive GP IC + IMRT concurrent with cisplatin chemotherapy and anti-PD-1 therapy (sintilimab) + anti-PD-1 therapy (sintilimab) AC. All patients will receive concurrent cisplatin (100 mg/m2) and sintilimab (200 mg, IV drop 30-60 min) every 3 weeks in a total of three cycles. All patients will receive adjuvant anti-PD-1 therapy (sintilimab, 200 mg, IV drop 30-60 min, q3w) in a total of nine cycles until disease progression, or intolerable toxicity or 6 months.

Drug: sintilimab

Interventions

sintilimab DRUG

Investigate whether capecitabine would be able to improve prognosis in patients at high risk groups

Arm II

Capecitabine DRUG

Investigate whether capecitabine would be able to improve prognosis in patients at intermediate risk groups

Arm I

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed, pathologically proven World Health Organization (WHO) type II/III untreated LANPC;
• LANPC (except T3N0, according to the 8th edition of the AJCC/UICC clinical staging system);
• Age at diagnosis: 18-65 years;
• Eastern Cooperative Oncology Group (ECOG) score: 0-1
• Receiving recommended three cycles of induction chemotherapy (IC) (gemcitabine-cisplatin \[GP\] regimen);
• 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;
• 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;
• Female subjects capable of becoming pregnant agree to use reliable contraceptive measures from screening to 1 year after treatment;
• 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.

You may not qualify if:

• Receiving surgery, target therapy, and/or immunotherapy during or before induction phase;
• Hepatitis B surface antigen-positive \[HBsAg(+)\],hepatitis B virus (HBV) DNA \> 1×103 copy/mL; hepatitis C virus (HCV) antibody(+);
• Other previous or concurrent malignant tumors, except adequately treated non-melanoma skin cancer, cervical carcinoma in situ, and thyroid papillary cancer;
• Pregnant or lactating women (a pregnancy test should be considered for fertile women with an active sex life);
• Previously treated with radical radiotherapy (RT), except non-melanoma skin cancers outside intended RT treatment volume;
• 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;
• 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);
• Received live vaccine within 1 month before treatment initiation;
• Allergy to macromolecular protein preparations, or any component of sintilimab;
• Human immunodeficiency virus (HIV)-positive or diagnosed with Acquired Immune Deficiency Syndrome (AIDS).

Sponsors & Collaborators

• Sun Yat-sen University: lead
• National Cancer Centre, Singapore: collaborator
• Wuzhou Red Cross Hospital: collaborator
• First People's Hospital of Foshan: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

sintilimab; Capecitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ying Sun, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice president

Study Record Dates

• First Submitted: August 24, 2019
• First Posted: August 28, 2019
• Study Start: June 1, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)