Nasopharyngeal CarcinomaPhase 2EP-STARNCT04072107
EPstein-barr Virus DNA Response to Systemic Therapy for Treatment Adaptation in High Risk NPC (EP-STAR)
A Phase 2 study testing sintilimab and Capecitabine in people with Nasopharyngeal Carcinoma, run by Sun Yat-sen University at 1 site in China.
Trial 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 . Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nasopharyngeal Carcinoma
- What is being tested?
- sintilimab and Capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2020to 1 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Nasopharyngeal Carcinoma
- Being tested
- sintilimab, Capecitabine
- Keywords
- nasopharyngeal carcinoma, EBV DNA, Biomarker-guided, Treatment adaptation
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sintilimabDrug
Investigate whether capecitabine would be able to improve prognosis in patients at high risk groups
CapecitabineDrug
Investigate whether capecitabine would be able to improve prognosis in patients at intermediate risk groups
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 year
Secondary outcomes (6)
overall survival
measured from the day of enrollment until death due to any cause, or the last follow-up visit.
Measured: 2 year
Distant metastasis failure-free survival
measured from the day of enrollment until death until distant metastasis , or the last follow-up visit.
Measured: 2 year
Locoregional failure-free survival
measured from the day of enrollment until death until local and/or regional recurrence, or the last follow-up visit.
Measured: 2 year
Adverse events
The incidence of immune-related and other adverse events
Measured: up to 5 years
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)
Measured: up to 2 years
Biomarker analysis
Exploratory biomarker analysis that would be able to predict patient treatment benefits, for example PD-L1 expression, tumor mutational burden, etc.
Measured: Through study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start1 Jun 2020
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Centre, Singapore, Wuzhou Red Cross Hospital, First People's Hospital of Foshan
- Responsible party
- Principal investigator, Ying Sun, Sun Yat-sen University
- Investigators
- Ying Sun, M.D., Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04072107
- Sponsor's protocol ID
- B2019-185-01
- Acronym
- EP-STAR
- Status last verified
- Jun 2023
- First submitted
- 24 Aug 2019
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Currently, there is no plan to make individual participant data (IPD) available to other researchers.
Publications
Lv J, Zheng DX, Liang JH, Zhang N, Ye ZL, Xu XD, Chua MLK, Zhang LL, Du ZM, Zhang ZC, Li WF, Tang LL, Chen L, Mao YP, Guo R, Chen YP, Lin L, Zhang Y, Liu X, Xu C, Li ZX, Xu LX, Yang PY, Chen K, Bin D, Gao TS, Yan JY, Chen LS, Huang SH, Zhao HY, Hong SB, Jie YS, Huang HL, Tang XH, Yun JP, Liu LZ, Tian L, Li HJ, Li JB, Zhou GQ, Ma J, Sun Y. Risk-adaptive therapy guided by dynamic ctDNA in nasopharyngeal carcinoma. Nature. 2026 Apr;652(8110):731-739. doi: 10.1038/s41586-026-10244-w. Epub 2026 Mar 11.
PubMed 41813900
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04072107
- Acronym / sponsor ID
- EP-STAR / B2019-185-01
- Conditions
- Nasopharyngeal Carcinoma
- Keywords
- nasopharyngeal carcinoma, EBV DNA, Biomarker-guided, Treatment adaptation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- National Cancer Centre, Singapore, Wuzhou Red Cross Hospital, First People's Hospital of Foshan
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 28 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: CapecitabinePatients 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. |
| Arm II | Experimental | Drug: sintilimabPatients 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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);
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sintilimabInvestigate whether capecitabine would be able to improve prognosis in patients at high risk groups | Drug | Arm II |
| CapecitabineInvestigate whether capecitabine would be able to improve prognosis in patients at intermediate risk groups | Drug | Arm I |
Primary outcome
Failure-free survival
Time frame: 2 year
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.
6 secondary outcomes
overall survival
Time frame: 2 year
Distant metastasis failure-free survival
Time frame: 2 year
Locoregional failure-free survival
Time frame: 2 year
Adverse events
Time frame: up to 5 years
Patient reported quality-of-life score
Time frame: up to 2 years
Biomarker analysis
Time frame: Through study completion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Derived from this study: PubMed 41813900Lv J, Zheng DX, Liang JH, Zhang N, Ye ZL, Xu XD, Chua MLK, Zhang LL, Du ZM, Zhang ZC, Li WF, Tang LL, Chen L, Mao YP, Guo R, Chen YP, Lin L, Zhang Y, Liu X, Xu C, Li ZX, Xu LX, Yang PY, Chen K, Bin D, Gao TS, Yan JY, Chen LS, Huang SH, Zhao HY, Hong SB, Jie YS, Huang HL, Tang XH, Yun JP, Liu LZ, Tian L, Li HJ, Li JB, Zhou GQ, Ma J, Sun Y. Risk-adaptive therapy guided by dynamic ctDNA in nasopharyngeal carcinoma. Nature. 2026 Apr;652(8110):731-739. doi: 10.1038/s41586-026-10244-w. Epub 2026 Mar 11.
- Individual participant dataSharing planned: No. Currently, there is no plan to make individual participant data (IPD) available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ying Sun, M.D. principal investigator
Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sintilimab and Capecitabine in people with Nasopharyngeal Carcinoma, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Failure-free survival (time frame: 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04072107, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2023.