Nasopharyngeal CarcinomaNCT05517135
tReatment Individualisation By EBV stratificatiON in Nasopharyngeal Carcinoma: an Umbrella Platform Study (RIBBON-Umbrella)
An observational study of Nasopharyngeal Carcinoma, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
This is a prospective platform study that will investigate the outcomes of patients with locoregionally-advanced nasopharyngeal carcinoma (LA-NPC) or recurrent-metastatic nasopharyngeal carcinoma (RM-NPC) who are assigned to treatment arms of different chemotherapy sequencing and intensity based on their pre- and… Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Nasopharyngeal Carcinoma
- What is being tested?
- Arm 1, Arm 2 and Arm 3
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 1,000 participants
- Where
- 1 siteSingapore
- Study dates
- 17 Nov 2022to 1 Jul 2027
- Phase
- Observational
- 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 21 to 99 years
- All sexes
- Adult, Older adult
Study population: Patients with suspected NPC or histologically confirmed NPC will be recruited for the study. Patients with confirmed stage 2-4B NPC will be enrolled into the platform study.
Who may be able to join
- Each patient eligible to participate in this study must meet all the following criteria:
- Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments.
- Age ≥21 years on the day of signing the ICF
- Fulfil one of the following three scenarios:
- Suspected NPC cases, diagnosed clinically based on symptoms (neck swelling, unilateral epistaxis, nasal obstruction etc.)
- Newly-diagnosed, histologically confirmed NPC patients with Stages 2-4A disease based on the AJCC/UICC 8th Edition TNM stage classification
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- Newly-diagnosed patients with RM-NPC
- All confirmed NPC patients must meet these additional criteria before they can continue participation in the study:
- NPC associated with EBV infection, determined as:
- The presence of EBV has been confirmed in the tumour by immunohistochemistry for EBV antigens or in situ hybridization for EBV early RNA (EBER), or
- NPC occurred in association with a raised serum titre of IgA to EBV viral capsid antigen (VCA) or early antigen (EA) in a patient living in endemic area of high incidence of EBV+ undifferentiated NPC, or
- NPC in the context of an elevated circulating EBV genome level
- AJCC 8th edition stage 2-4A or RM NPC based on the following diagnostic workup:
- Evaluation of tumour extent with magnetic resonance imaging (MRI) of the nasopharynx and neck. If MRI is medically contraindicated, computed tomography (CT) scan with ≤3 mm and intravenous contrast is acceptable.
- Distant metastasis staging:
- CT scan with contrast of the chest, abdomen, and pelvis or a total body 18F-Fluorodeoxygenase positron emission tomography CT (18F-FDG-PET-CT) scan;
- Bone scan, if a 18F-FDG-PET-CT scan is not performed.
- ECOG Performance Status ≤1
- Adequate organ function
Who cannot join
- Patients who meet any of the following criteria are not eligible to enrol:
- Age <21 years or >99 years old
- Has received any prior RT or systemic anti-cancer therapy including investigational agents that are not part of the intended treatment plan for NPC
- Any known central nervous system metastases and/or carcinomatous meningitis
- Any active malignancy ≤2 years before start of study except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
- Patients with severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
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- Severe infections within 4 weeks before start of study, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is >500 IU/mL or patients with active hepatitis C virus (HCV) should be excluded.
- Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA <500 IU/mL), and cured hepatitis C patients can be enrolled
- Prior allogeneic stem cell transplantation or organ transplantation
- Any of the following cardiovascular risk factors:
- Cardiac chest pain, defined as moderate pain or any cardiac condition e.g., arrhythmias, malignant hypertension, etc. that limits instrumental activities of daily living, ≤28 days before start of study
- Pulmonary embolism ≤28 days before start of study
- Any history of cerebrovascular accident or seizure ≤ 28 days before start of study
- A history of severe hypersensitivity reactions to gemcitabine, cisplatin, capecitabine and/or any of its excipients
- Has received any herbal medicine used to control cancer within 14 days of the start of study
- Patients with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline or stabilized, except for adverse events (AEs) not considered a likely safety risk (eg, alopecia, neuropathy and specific laboratory abnormalities)
- Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that, will be unfavorable for the administration of treatment or affect the explanation of drug toxicity or AEs or result in insufficient or might impair compliance with study conduct
- Concurrent participation in another therapeutic clinical study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
National Cancer Centre Singapore
Singapore, 168583
About this study
This is a prospective platform study that will investigate the outcomes of patients with locoregionally-advanced nasopharyngeal carcinoma (LA-NPC) or recurrent-metastatic nasopharyngeal carcinoma (RM-NPC) who are assigned to treatment arms of different chemotherapy sequencing and intensity based on their pre- and on-treatment plasma EBV DNA results.
Read the detailed description
The primary objectives of this platform are: (1) to prospectively validate the prognostic potential of an EBV DNA-based risk-stratification strategy of patients with LA- and RM-NPC; and (2) to test if treatment individualization strategies based on pre- and on-treatment plasma EBV DNA will improve survival outcomes.
For LA-NPC, the study design consists of two components: (1) to allocate adult patients with UICC/AJCC 8th edition TNM-stage 2-4A LA-NPC to 3 treatment arms of different intensities by their plasma EBV DNA levels pre-treatment and post-induction chemotherapy (IC); and (2) to incorporate open-label, single-arm, phase 2 trials within the platform for patients who are deemed to be at high-risk of relapse, defined by a persistently detectable EBV DNA following 3 cycles of IC. Primary study end-point is 2-year disease-free survival (DFS).
- Conditions
- Nasopharyngeal Carcinoma
- Being tested
- Arm 1, Arm 2, Arm 3, Group 1, Group 2
- Keywords
- Nasopharyngeal Carcinoma, EBV DNA, Biomarker-guided, Treatment Individualization, Risk Stratification
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm 1Other
Concurrent chemoradiotherapy (CCRT) using cisplatin (100 mg/m2 IV) or carboplatin (AUC 5 IV) with radiotherapy +/- adjuvant chemotherapy (AC). For AC, physicians can choose between cisplatin-5FU d1-4, q4w for 3 cycles, or capecitabine 650 mg/m2 bid for 12 months or 1000 mg/m2 bid oral, d1-21, q3w for 6 months
Arm 2Other
IC using cisplatin (80 mg/m2 IV) or carboplatin (AUC 3-5 IV) in combination with gemcitabine (1000 mg/m2 d1,8) or 5-fluorouracil (1000 mg/m2 bolus IV d1-4) or docetaxel (75 mg/m2 IV), and CCRT +/- metronomic capecitabine (650 mg/m2 bid oral for 12 months)
Arm 3Other
IC using cisplatin (80 mg/m2 IV) or carboplatin (AUC 3-5 IV) in combination with gemcitabine (1000 mg/m2 d1,8) or 5-fluorouracil (1000 mg/m2 bolus IV d1-4) or docetaxel (75 mg/m2 IV), followed by either of the following:
- RIBBON-LA-01 (NCT06093061)
- CCRT + metronomic capecitabine (650 mg/m2 bid oral for 12 months)
Group 1Other
Combination chemotherapy (using cisplatin or carboplatin with gemcitabine, 5-fluorouracil or docetaxel) and consolidative RT to the nasopharynx and neck (if good response to chemotherapy) +/- metastasis-directed therapy (surgery, radiofrequency ablation or RT) +/- immune checkpoint blockade (ICB) or capecitabine
Group 2Other
Combination chemotherapy (using cisplatin or carboplatin with gemcitabine, 5-fluorouracil or docetaxel) with or without ICB +/- maintenance ICB or capecitabine
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Arm 1: Pre-treatment EBV DNA <4000 copies/mL AND N0-1 or T4N0 (TNM AJCC/UICC 8th edition) Receives: Other: Arm 1 | |
| Arm 2 | Arm 2: Pre-treatment EBV DNA ≥4000 copies/mL OR N2-N3 OR T4N+ (TNM AJCC/UICC 8th edition) AND EBV DNA UNDETECTABLE after 2-3 cycles of induction chemotherapy (IC) Receives: Other: Arm 2 | |
| Arm 3 | Arm 3: Pre-treatment EBV DNA ≥4000 copies/mL OR N2-N3 OR T4N+ (TNM AJCC/UICC 8th edition) AND EBV DNA DETECTABLE after 2-3 cycles of IC Receives: Other: Arm 3 | |
| Group 1 | Group 1: Recurrent/metastatic NPC, EBV DNA <4000 copies/mL Receives: Other: Group 1 | |
| Group 2 | Group 2: Recurrent/metastatic NPC, EBV DNA ≥4000 copies/mL Receives: Other: Group 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-Free Survival
Measured: 2 years from end of treatment
Secondary outcomes (5)
Overall survival
Measured: 2 years after end of treatment
Distant metastasis-free survival
Measured: 2 years after end of treatment
Loco-regional recurrence-free survival
Measured: 2 years after end of treatment
Treatment-related adverse events
Measured: From start of treatment to 30 days after last treatment and up to 5 years post - treatment
Genome sequencing of biological samples
Blood samples will be collected at up to 7 timepoints - baseline, mid/post IC, mid CCRT, 1-2 weeks post-RT, 3 months post-RT/mid-adjuvant chemotherapy, at point of recurrence and post immune checkpoint blockade treatment (ICB) for recurrence, if any; fresh biopsy samples will be collected at baseline, mid-IC, at point of recurrence and mid-ICB, if amenable for biopsy. Saliva samples will be collected at baseline and at point of recurrence.
Measured: baseline, mid/post IC, mid CCRT, 1-2 weeks post-RT, 3 months post-RT/mid-adjuvant chemotherapy, at point of recurrence and post immune checkpoint blockade treatment (for recurrence, if any) up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2022
- Study start17 Nov 2022
- Primary completion1 Jul 2027 (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 CarcinomaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Melvin Lee Kiang Chua, MBBS, FRCR, PhD, FAMS, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05517135
- Sponsor's protocol ID
- 2022/2315
- Status last verified
- Sep 2024
- First submitted
- 23 Aug 2022
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- tReatment Individualisation By EBV stratificatiON in Nasopharyngeal Carcinoma: an Umbrella Platform Study (RIBBON-Umbrella)
- ClinicalTrials.gov ID
- NCT05517135
- Acronym / sponsor ID
- 2022/2315
- Conditions
- Nasopharyngeal Carcinoma
- Keywords
- Nasopharyngeal Carcinoma, EBV DNA, Biomarker-guided, Treatment Individualization, Risk Stratification
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- 17 Nov 2022 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 26 Aug 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.
This is a prospective platform study that will investigate the outcomes of patients with locoregionally-advanced nasopharyngeal carcinoma (LA-NPC) or recurrent-metastatic nasopharyngeal carcinoma (RM-NPC) who are assigned to treatment arms of different chemotherapy sequencing and intensity based on their pre- and on-treatment plasma EBV DNA results.
Detailed description
The primary objectives of this platform are: (1) to prospectively validate the prognostic potential of an EBV DNA-based risk-stratification strategy of patients with LA- and RM-NPC; and (2) to test if treatment individualization strategies based on pre- and on-treatment plasma EBV DNA will improve survival outcomes.
For LA-NPC, the study design consists of two components: (1) to allocate adult patients with UICC/AJCC 8th edition TNM-stage 2-4A LA-NPC to 3 treatment arms of different intensities by their plasma EBV DNA levels pre-treatment and post-induction chemotherapy (IC); and (2) to incorporate open-label, single-arm, phase 2 trials within the platform for patients who are deemed to be at high-risk of relapse, defined by a persistently detectable EBV DNA following 3 cycles of IC. Primary study end-point is 2-year disease-free survival (DFS).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | – | Other: Arm 1Arm 1: Pre-treatment EBV DNA <4000 copies/mL AND N0-1 or T4N0 (TNM AJCC/UICC 8th edition) |
| Arm 2 | – | Other: Arm 2Arm 2: Pre-treatment EBV DNA ≥4000 copies/mL OR N2-N3 OR T4N+ (TNM AJCC/UICC 8th edition) AND EBV DNA UNDETECTABLE after 2-3 cycles of induction chemotherapy (IC) |
| Arm 3 | – | Other: Arm 3Arm 3: Pre-treatment EBV DNA ≥4000 copies/mL OR N2-N3 OR T4N+ (TNM AJCC/UICC 8th edition) AND EBV DNA DETECTABLE after 2-3 cycles of IC |
| Group 1 | – | Other: Group 1Group 1: Recurrent/metastatic NPC, EBV DNA <4000 copies/mL |
| Group 2 | – | Other: Group 2Group 2: Recurrent/metastatic NPC, EBV DNA ≥4000 copies/mL |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients with suspected NPC or histologically confirmed NPC will be recruited for the study. Patients with confirmed stage 2-4B NPC will be enrolled into the platform study.
Key inclusion criteria (19 listed)
- Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments.
- Age ≥21 years on the day of signing the ICF
- Fulfil one of the following three scenarios:
- All confirmed NPC patients must meet these additional criteria before they can continue participation in the study:
- NPC associated with EBV infection, determined as:
Key exclusion criteria (19 listed)
- Age <21 years or >99 years old
- Has received any prior RT or systemic anti-cancer therapy including investigational agents that are not part of the intended treatment plan for NPC
- Any known central nervous system metastases and/or carcinomatous meningitis
- Any active malignancy ≤2 years before start of study except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
- Patients with severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc.
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 |
|---|---|---|
| Arm 1Concurrent chemoradiotherapy (CCRT) using cisplatin (100 mg/m2 IV) or carboplatin (AUC 5 IV) with radiotherapy +/- adjuvant chemotherapy (AC). For AC, physicians can choose between cisplatin-5FU d1-4, q4w for 3 cycles, or capecitabine 650 mg/m2 bid for 12 months or 1000 mg/m2 bid oral, d1-21, q3w for 6 months | Other | Arm 1 |
| Arm 2IC using cisplatin (80 mg/m2 IV) or carboplatin (AUC 3-5 IV) in combination with gemcitabine (1000 mg/m2 d1,8) or 5-fluorouracil (1000 mg/m2 bolus IV d1-4) or docetaxel (75 mg/m2 IV), and CCRT +/- metronomic capecitabine (650 mg/m2 bid oral for 12 months) | Other | Arm 2 |
| Arm 3IC using cisplatin (80 mg/m2 IV) or carboplatin (AUC 3-5 IV) in combination with gemcitabine (1000 mg/m2 d1,8) or 5-fluorouracil (1000 mg/m2 bolus IV d1-4) or docetaxel (75 mg/m2 IV), followed by either of the following: 1. RIBBON-LA-01 (NCT06093061) 2. CCRT + metronomic capecitabine (650 mg/m2 bid oral for 12 months) | Other | Arm 3 |
| Group 1Combination chemotherapy (using cisplatin or carboplatin with gemcitabine, 5-fluorouracil or docetaxel) and consolidative RT to the nasopharynx and neck (if good response to chemotherapy) +/- metastasis-directed therapy (surgery, radiofrequency ablation or RT) +/- immune checkpoint blockade (ICB) or capecitabine | Other | Group 1 |
| Group 2Combination chemotherapy (using cisplatin or carboplatin with gemcitabine, 5-fluorouracil or docetaxel) with or without ICB +/- maintenance ICB or capecitabine | Other | Group 2 |
Primary outcome
Disease-Free Survival
Time frame: 2 years from end of treatment
5 secondary outcomes
Overall survival
Time frame: 2 years after end of treatment
Distant metastasis-free survival
Time frame: 2 years after end of treatment
Loco-regional recurrence-free survival
Time frame: 2 years after end of treatment
Treatment-related adverse events
Time frame: From start of treatment to 30 days after last treatment and up to 5 years post - treatment
Genome sequencing of biological samples
Time frame: baseline, mid/post IC, mid CCRT, 1-2 weeks post-RT, 3 months post-RT/mid-adjuvant chemotherapy, at point of recurrence and post immune checkpoint blockade treatment (for recurrence, if any) up to 5 years
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 19 Sep 2024.
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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.
Melvin Lee Kiang Chua, MBBS, FRCR, PhD, FAMS principal investigator
National Cancer Centre, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Nasopharyngeal Carcinoma, run by National Cancer Centre, Singapore at 1 site in Singapore.
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 19 inclusion and 19 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 19 Sep 2024. 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 Singapore. 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.
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 Melvin Lee Kiang Chua, MBBS, FRCR, PhD, FAMS (64368000, melvin.chua.l.k@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-Free Survival (time frame: 2 years from end of treatment). 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 19 Sep 2024; AzTrials last refreshed its copy on 8 Nov 2026.