Modulation Therapy for Locally Advanced NPC Based on Plasma EBV DNA Level Post-ICT

NCT05628922 | Recruiting Phase 2 DMC

• 1 other identifier: Remodel 1.0
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

Nasopharyngeal carcinoma is biologically different from traditional head and neck squamous cell carcinoma. The mainstay treatment for locally advanced nasopharyngeal carcinoma is cisplatin-based concurrent chemoradiation. Recent phase III randomized control trials have demonstrated that induction chemotherapy plus concurrent chemoradiation further improved progression-free survival. However, not every patient has good response to induction chemotherapy. Evidence has accumulated that those with poor response to induction chemotherapy, or those with detectable Epstein-Barr Virus (EBV) DNA post induction chemotherapy, correlated with poorer progression-free survival. Huang CL et al. (Int J Radiat Oncol Bio Phys. 2019) reported that plasma EBV DNA load at completion of induction chemotherapy was an independent and earlier predictor for progression-free survival and overall survival in locally advanced nasopharyngeal carcinoma. Lv J et al. (Nat Commun. 2019) demonstrated that real-time monitoring of plasma EBV DNA response added prognostic information, and had the potential uitility for risk-adapted treatment intensification in nasopharyngeal carcinoma. Therefore, investigators selects those with poor plasma EBV DNA response during and after induction chemotherapy, and intensifies the treatment with combination of anti-PD-1 antibody, in order to improve progression-free survival in locally advanced nasopharyngeal carcinoma, according to response-adapted strategy.

Conditions

Nasopharyngeal Cancer

Keywords

Epstein-Barr virus DNA; Immunotherapy; Programmed Cell Death 1 antibody; Induction chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  the time from the date of enrollment to progression of disease

  2 year

Secondary Outcomes (6)

• Overall survival

  2 year

• Locoregional recurrence-free survival

  2 year

• Distant metastasis-free survival

  2 year

• Adverse effects

  up to 2 year

• Quality of Life

  up to 2 year

Study Arms (3)

Early Responders

EXPERIMENTAL

those with undetectable plasma EBV DNA after first cycle of induction chemotherapy (GP regimen)

Other: Induction chemotherapy and concurrent chemoradiation

Intermediate Responders

EXPERIMENTAL

those with detectable plasma EBV DNA after first cycle of induction chemotherapy (GP regimen), and undetectable plasma EBV DNA at completion of induction chemotherapy

Drug: Toripalimab; Other: Induction chemotherapy and concurrent chemoradiation

Late Responders

EXPERIMENTAL

those with detectable plasma EBV DNA after first cycle and at completion of induction chemotherapy (GP regimen)

Drug: Toripalimab; Other: Induction chemotherapy and concurrent chemoradiation

Interventions

Toripalimab DRUG

Early Responders: They receive the second and third cycle of induction chemotherapy (GP regimen), followed by cisplatin-based concurrent chemoradiation. Intermediate Responders: they received the second and third cycle of induction chemotherapy (GP regimen) with combination of toripalimap (240mg d1, q3w \* 2 cycles), followed by cisplatin-based concurrent chemoradiation. Late responders: they received the second and third cycle of induction chemotherapy (GP regimen) with combination of toripalimap (240mg d1, q3w \* 2 cycles), followed by cisplatin-based concurrent chemoradiation. At 4-6 weeks post-chemoradiation, they received adjuvant capecitabine and toripalimab for 6 months.

Also known as: JS001

Intermediate Responders; Late Responders

Induction chemotherapy and concurrent chemoradiation OTHER

Induction chemotherapy (GP regimen) and cisplatin-based concurrent chemoradiation. GP regimen: Gemcitabine 1.0 g d1,d8, cisplatin 25mg/m2 d1-3 q3w Cisplatin based chemotherapy: cisplatin 80mg/m2 given in three consecutive days, q3w \* 2 cycles.

Early Responders; Intermediate Responders; Late Responders

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must sign the informed consent form, and must be willing and able to comply with the visits, treatment regimen, laboratory tests and other requirements specified in the study protocol;
• Age at diagnosis: 18-70 years old;
• Firstly diagnosed, pathologically confirmed primary nasopharyngeal carcinoma with "non-keratinizing carcinoma (WHO criteria)";
• Locally advanced nasopharyngeal carcinoma (T3-4N0-1M0, TanyN2-3M0), staged according to the American Joint Committee on Cancer (AJCC) 8th edition clinical staging system;
• Pretreatment EBV DNA \>0;
• ECOG score: 0-1 points;
• Does not receive any treatment after the diagnosis of nasopharyngeal carcinoma;
• Normal bone marrow function: white blood cell \>4\*109/L, neutrophil count \>1.5\*109/L, hemoglobin concentration \> 90g/L, platelet count \>100\*109/L;
• Normal liver and kidney function: total bilirubin ≤1.5 times the upper limit of normal; aspartate aminotransferase and/or alanine aminotransferase ≤ 2.5 times the upper limit of normal; creatinine clearance ≥ 60mL/min;
• For those with hepatitis B infection, the HBV DNA load must be \< 2500 copies/ml at the time of screening; For those with anti-hepatitis C virus antibody, HCV RNA must be negative at the time of screening;
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use reliable contraception (e.g. condoms, regular contraceptives as directed) from screening through 1 year after treatment.

You may not qualify if:

• Pathologically confirmed primary nasopharyngeal carcinoma with "keratinizing carcinoma or basaloid squamous cell carcinoma";
• Previous or current other malignancy other than adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma;
• Pretreatment plasma EBV DNA undetectable;
• History of radiation therapy prior to standard therapy (except for non-melanoma skin cancer, and the previous radiation field did not overlap with the current treatment for nasopharyngeal carcinoma);
• Patients who received surgical treatment (except for diagnostic biopsy), biological therapy, chemotherapy or immunotherapy before enrollment;
• Conditions mentioned below: 1) Currently enrolled in other interventional clinical trial; 2) Systemic hormonal or other immunosuppressive therapy with an equivalent dose of \> 10mg prednisone/day within 28 days prior to informed consent; 3) Receipt of live vaccines within 30 days prior to enrollment; 4) Surgery or trauma within 30 days prior to enrollment;
• Uncontrolled heart disease, such as :1) heart failure, NYHA ≥ 2; 2) unstable angina; 3) history of myocardial infarction within 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention;
• History of stroke within 6 months;
• Patients with severe active infection within 30 days prior to enrollment, that must be treated with systemic antibacterial, antifungal or antiviral therapy;
• Active autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary disease, nephritis, vasculitis, hyperthyroidism, etc.). Except for type I diabetes, hypothyroidism requiring hormone replacement therapy, and vitiligo not requiring systemic treatment, inactive childhood asthma that does not require treatment as an adult;
• Positive anti-HIV antibody or diagnosis of other innate or acquired immunodeficient, immunosuppressive disease, history of organ transplantation;
• Interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy within 1 year;
• Active tuberculosis infection, or previous lung tuberculosis infection within 1 year, or previous lung tuberculosis infection more than 1 year prior to enrollment but did not receive standard anti-tuberculosis treatment;
• Positive hepatitis B surface antigen and hepatitis B virus DNA ≥ 2500 copies/ml or Positive hepatitis C RNA;
• Pregnant or lactating women (pregnancy test should be considered for sexually active women of childbearing age);

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan Universtiy Shanghai Cancer Centre

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Neoplasms

Interventions

toripalimab; Induction Chemotherapy

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Remission Induction

Study Officials

• Chao-su Hu, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao-su Hu, M.D.

CONTACT

+862164175590; hucsu62@163.com

Xiaomin Ou, M.D.

CONTACT

+862164175590; 0456218@fudan.edu.cn

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: M.D., Professor

Study Record Dates

• First Submitted: June 11, 2022
• First Posted: November 29, 2022
• Study Start: July 2, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: November 29, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)