Nasopharyngeal CancerPhase 2NCT05628922
Modulation Therapy for Locally Advanced NPC Based on Plasma EBV DNA Level Post-ICT
A Phase 2 study testing Toripalimab and Induction chemotherapy and concurrent chemoradiation in people with Nasopharyngeal Cancer, run by Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Nasopharyngeal Cancer
- What is being tested?
- Toripalimab and Induction chemotherapy and concurrent chemoradiation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 1 siteChina
- Study dates
- 2 Jul 2022to 1 Jul 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Fudan Universtiy Shanghai Cancer Centre
Shanghai, Shanghai Municipality, 200032
Chaosu Hu, M.D., +8621-64175590 ext. 81400, hucsu62@163.com
About this study
Official title: Response-adapted Modulation Therapy for Locally Advanced Nasopharyngeal Carcinoma Based on Circulating Epstein-Barr Virus DNA Level Post Induction Chemotherapy
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.
Read the 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.
- Conditions
- Nasopharyngeal Cancer
- Being tested
- Toripalimab, Induction chemotherapy and concurrent chemoradiation
- Keywords
- Epstein-Barr virus DNA, Immunotherapy, Programmed Cell Death 1 antibody, Induction chemotherapy
- Medical subject headings
- Nasopharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Also called JS001
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.
Induction chemotherapy and concurrent chemoradiationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Early Responders | Experimental | those with undetectable plasma EBV DNA after first cycle of induction chemotherapy (GP regimen) Receives: 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 Receives: 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) Receives: Drug: Toripalimab; Other: Induction chemotherapy and concurrent chemoradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
the time from the date of enrollment to progression of disease
Measured: 2 year
Secondary outcomes (6)
Overall survival
the time from the date of enrollment to death
Measured: 2 year
Locoregional recurrence-free survival
the time from date of enrollment to locoregional recurrence
Measured: 2 year
Distant metastasis-free survival
the time from date of enrollment to distant metastasis
Measured: 2 year
Adverse effects
evaluated according to CTCAE 5.0 version
Measured: up to 2 year
Quality of Life
evaluated according to EORTC QLQ-C30
Measured: up to 2 year
Quality of Life
evaluated according to EORTC QLQ-H\&N35
Measured: up to 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2022
- Study start2 Jul 2022
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nasopharyngeal CancerStudies of the same condition, open and under way.
- More trials run by Fudan 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
- 198 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chaosu Hu, Fudan University
- Investigators
- Chao-su Hu, M.D., Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05628922
- Sponsor's protocol ID
- Remodel 1.0
- Status last verified
- Nov 2022
- First submitted
- 11 Jun 2022
- Last updated
- 29 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response-adapted Modulation Therapy for Locally Advanced Nasopharyngeal Carcinoma Based on Circulating Epstein-Barr Virus DNA Level Post Induction Chemotherapy
- ClinicalTrials.gov ID
- NCT05628922
- Acronym / sponsor ID
- Remodel 1.0
- Conditions
- Nasopharyngeal Cancer
- Keywords
- Epstein-Barr virus DNA, Immunotherapy, Programmed Cell Death 1 antibody, Induction chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 198 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 2 Jul 2022 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 29 Nov 2022 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Early Responders | Experimental | Other: Induction chemotherapy and concurrent chemoradiationthose with undetectable plasma EBV DNA after first cycle of induction chemotherapy (GP regimen) |
| Intermediate Responders | Experimental | Drug: Toripalimab, Other: Induction chemotherapy and concurrent chemoradiationthose with detectable plasma EBV DNA after first cycle of induction chemotherapy (GP regimen), and undetectable plasma EBV DNA at completion of induction chemotherapy |
| Late Responders | Experimental | Drug: Toripalimab, Other: Induction chemotherapy and concurrent chemoradiationthose with detectable plasma EBV DNA after first cycle and at completion of induction chemotherapy (GP regimen) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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;
Key exclusion criteria (16 listed)
- 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;
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 |
|---|---|---|
| ToripalimabAlso: JS001Early 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. | Drug | Intermediate Responders, Late Responders |
| Induction chemotherapy and concurrent chemoradiationInduction 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. | Other | Early Responders, Intermediate Responders, Late Responders |
Primary outcome
Progression-free survival
Time frame: 2 year
the time from the date of enrollment to progression of disease
6 secondary outcomes
Overall survival
Time frame: 2 year
Locoregional recurrence-free survival
Time frame: 2 year
Distant metastasis-free survival
Time frame: 2 year
Adverse effects
Time frame: up to 2 year
Quality of Life
Time frame: up to 2 year
Quality of Life
Time frame: up to 2 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2022.
- Individual participant dataSharing planned: No
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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.
Chao-su Hu, M.D. principal investigator
Fudan 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 Toripalimab and Induction chemotherapy and concurrent chemoradiation in people with Nasopharyngeal Cancer, run by Fudan 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 11 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 29 Nov 2022. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chao-su Hu, M.D. (+862164175590 ext. 81400, hucsu62@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-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?
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 29 Nov 2022.