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

Primary Purpose

Nasopharyngeal Carcinoma

Status

Active

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

sintilimab

Capecitabine

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring nasopharyngeal carcinoma, EBV DNA, Biomarker-guided, Treatment adaptation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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;
*For patients recruited to Arm II, the additional exclusion criteria are:
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).

Sites / Locations

Sun Yat-sen University Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm I

Arm II

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

overall survival

measured from the day of enrollment until death due to any cause, or the last follow-up visit.

Distant metastasis failure-free survival

measured from the day of enrollment until death until distant metastasis , or the last follow-up visit.

Locoregional failure-free survival

measured from the day of enrollment until death until local and/or regional recurrence, or the last follow-up visit.

Adverse events

The incidence of immune-related and other adverse events

Patient reported quality-of-life score

Patient reported quality of life would be evaluated using the Quality of Life Questionnaire-Core 30 module (QLQ-C30)

Biomarker analysis

Exploratory biomarker analysis that would be able to predict patient treatment benefits, for example PD-L1 expression, tumor mutational burden, etc.

Full Information

NCT ID

NCT04072107

First Posted

August 24, 2019

Last Updated

June 16, 2023

Sponsor

Sun Yat-sen University

Collaborators

National Cancer Centre, Singapore, Wuzhou Red Cross Hospital, First People's Hospital of Foshan

1. Study Identification

Unique Protocol Identification Number

NCT04072107

Brief Title

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

Acronym

EP-STAR

Official Title

Epstein-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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 1, 2020 (Actual)

Primary Completion Date

December 1, 2024 (Anticipated)

Study Completion Date

December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

Collaborators

National Cancer Centre, Singapore, Wuzhou Red Cross Hospital, First People's Hospital of Foshan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nasopharyngeal Carcinoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Experimental

Arm Description

Arm Title

Arm II

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

sintilimab

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Intervention Description

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

Primary Outcome Measure Information:

Title

Failure-free survival

Description

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.

Time Frame

2 year

Secondary Outcome Measure Information:

Title

overall survival

Description

measured from the day of enrollment until death due to any cause, or the last follow-up visit.

Time Frame

2 year

Title

Distant metastasis failure-free survival

Description

measured from the day of enrollment until death until distant metastasis , or the last follow-up visit.

Time Frame

2 year

Title

Locoregional failure-free survival

Description

measured from the day of enrollment until death until local and/or regional recurrence, or the last follow-up visit.

Time Frame

2 year

Title

Adverse events

Description

The incidence of immune-related and other adverse events

Time Frame

up to 5 years

Title

Patient reported quality-of-life score

Description

Patient reported quality of life would be evaluated using the Quality of Life Questionnaire-Core 30 module (QLQ-C30)

Time Frame

up to 2 years

Title

Biomarker analysis

Description

Exploratory biomarker analysis that would be able to predict patient treatment benefits, for example PD-L1 expression, tumor mutational burden, etc.

Time Frame

Through study completion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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; *For patients recruited to Arm II, the additional exclusion criteria are: 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ying Sun, M.D.

Organizational Affiliation

Sun Yat-sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Currently, there is no plan to make individual participant data (IPD) available to other researchers.

Learn more about this trial

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

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