search
Back to results

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

Primary Purpose

Nasopharyngeal Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Toripalimab
Induction chemotherapy and concurrent chemoradiation
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Cancer focused on measuring Epstein-Barr virus DNA, Immunotherapy, Programmed Cell Death 1 antibody, Induction chemotherapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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); Other conditions that may jeopardize patient safety or compliance as assessed by investigator, such as serious illness (including psychiatric disorders) requiring prompt treatment, severely abnormal test results, and other family or social risk factors.

Sites / Locations

  • Fudan Universtiy Shanghai Cancer CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Early Responders

Intermediate Responders

Late Responders

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Progression-free survival
the time from the date of enrollment to progression of disease

Secondary Outcome Measures

Overall survival
the time from the date of enrollment to death
Locoregional recurrence-free survival
the time from date of enrollment to locoregional recurrence
Distant metastasis-free survival
the time from date of enrollment to distant metastasis
Adverse effects
evaluated according to CTCAE 5.0 version
Quality of Life
evaluated according to EORTC QLQ-C30
Quality of Life
evaluated according to EORTC QLQ-H&N35

Full Information

First Posted
June 11, 2022
Last Updated
November 25, 2022
Sponsor
Fudan University
search

1. Study Identification

Unique Protocol Identification Number
NCT05628922
Brief Title
Modulation Therapy for Locally Advanced NPC Based on Plasma EBV DNA Level Post-ICT
Official Title
Response-adapted Modulation Therapy for Locally Advanced Nasopharyngeal Carcinoma Based on Circulating Epstein-Barr Virus DNA Level Post Induction Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 2, 2022 (Actual)
Primary Completion Date
July 1, 2026 (Anticipated)
Study Completion Date
July 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
In this study, investigators enroll patients with locally advanced nasopharyngeal carcinoma. All the patients recieve GP-based induction chemotherapy. After one cycle of induction chemotherapy, plasma EBV DNA and head and neck MR are performed. Based on clinical efficacy and changes of plasma EBV DNA, patients with good response will directly receive concurrent chemoradiation (CCRT). Patients with intermediate response will be randomized to immunotherapy group (GP combined with toripalimab for two additional cycles then CCRT) and standard group (GP for two additional cycles then CCRT). Patients with poor response will be switched to TP regimen combined with toripalimab, followed by CCRT. The main endpoint is 2 year progression-free survival rate. The aim of this study is to clarify whether response-adapted strategy based on clinical efficacy and EBV DNA response confers survival benefit to patients with locally advanced nasopharyngeal carcinoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Cancer
Keywords
Epstein-Barr virus DNA, Immunotherapy, Programmed Cell Death 1 antibody, Induction chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
198 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Early Responders
Arm Type
Experimental
Arm Description
those with undetectable plasma EBV DNA after first cycle of induction chemotherapy (GP regimen)
Arm Title
Intermediate Responders
Arm Type
Experimental
Arm Description
those with detectable plasma EBV DNA after first cycle of induction chemotherapy (GP regimen), and undetectable plasma EBV DNA at completion of induction chemotherapy
Arm Title
Late Responders
Arm Type
Experimental
Arm Description
those with detectable plasma EBV DNA after first cycle and at completion of induction chemotherapy (GP regimen)
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Other Intervention Name(s)
JS001
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Induction chemotherapy and concurrent chemoradiation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free survival
Description
the time from the date of enrollment to progression of disease
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Overall survival
Description
the time from the date of enrollment to death
Time Frame
2 year
Title
Locoregional recurrence-free survival
Description
the time from date of enrollment to locoregional recurrence
Time Frame
2 year
Title
Distant metastasis-free survival
Description
the time from date of enrollment to distant metastasis
Time Frame
2 year
Title
Adverse effects
Description
evaluated according to CTCAE 5.0 version
Time Frame
up to 2 year
Title
Quality of Life
Description
evaluated according to EORTC QLQ-C30
Time Frame
up to 2 year
Title
Quality of Life
Description
evaluated according to EORTC QLQ-H&N35
Time Frame
up to 2 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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); Other conditions that may jeopardize patient safety or compliance as assessed by investigator, such as serious illness (including psychiatric disorders) requiring prompt treatment, severely abnormal test results, and other family or social risk factors.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chao-su Hu, M.D.
Phone
+862164175590
Ext
81400
Email
hucsu62@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaomin Ou, M.D.
Phone
+862164175590
Ext
81400
Email
0456218@fudan.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chao-su Hu, M.D.
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan Universtiy Shanghai Cancer Centre
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chaosu Hu, M.D.
Phone
+8621-64175590
Ext
81400
Email
hucsu62@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs