Trial Title:
Tislelizumab and Metronomic Capecitabine as Maintenance in High-risk Locoregionally-advanced Nasopharyngeal Carcinoma
NCT ID:
NCT06093061
Condition:
Nasopharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Capecitabine
Tislelizumab
Conditions: Keywords:
Locoregionally-advanced NPC
EBV DNA
Concurrent chemoradiotherapy (CCRT)
Maintenance Tislelizumab
Metronomic Capecitabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
CCRT with Maintenance Tislelizumab and Metronomic Capecitabine
Description:
CCRT: Radiotherapy will be delivered once daily, for 5 days per week, over 6 to 7 weeks.
During RT, cisplatin will be administered either 100 mg/m2 3-weekly or 40 mg/m2 weekly,
IV infusion (physician's choice).
Maintenance: Tislelizumab 200mg, day 1 per 3-week cycle, intravenous (IV) infusion and
capecitabine 650 mg/m2, days 1-21 per 3-week cycle, bidaily, oral, for a total of 12
months (17 cycles).
Arm group label:
MAINTENANCE STUDY TREATMENT
Summary:
Patients with "high-risk" locoregionally-advanced nasopharyngeal carcinoma (LA-NPC),
defined as AJCC/UICC 8th edition TNM-stage III-IVA and high Epstein-Barr virus (EBV) DNA
viral load (≥4,000 copies/mL) will require induction chemotherapy (IC) prior to
chemo-radiation (CCRT) as per standard treatment. Patients who persist to manifest
DETECTABLE EBV DNA following 3 cycles of IC have a higher risk of relapse, and are
typically recommended for a year of low-dose oral chemotherapy after CCRT.
RIBBON-LA-01 is a single-arm, open-label, phase 2 clinical trial of maintenance
tislelizumab and metronomic capecitabine (metroCap) for 52 weeks after IC and CCRT,
targeting this specific group of patients who have persistent detectable EBV DNA after
IC. The main objective is to evaluate the efficacy of maintenance tislelizumab and
metroCap in patients with DETECTABLE EBV DNA levels after 3 cycles of IC.
Detailed description:
RIBBON-LA-01 is embedded in a modular platform trial concept (NCT05517135,
https://clinicaltrials.gov/study/NCT05517135) that tests if EBV DNA-based risk
stratification strategies for treatment individualization improves survival outcomes in
LA-NPC. The overarching platform trial concept allocates patients with LA-NPC to
treatment arms of different intensities by their plasma EBV DNA levels pre-treatment and
post-IC.
RIBBON-LA-01 enrolls patients allocated to Arm 3 of the platform trial; these are
patients with pre-treatment EBV DNA of >4,000 copies/mL OR N2-3 or T4N+ NPC who were
treated with upfront IC, but persist to manifest DETECTABLE EBV DNA levels following 3
cycles of IC. Patients on the trial will be assigned to CCRT followed by a 12-month
course of maintenance tislelizumab and metroCap.
The primary endpoint of the study is two-year disease free survival, defined as the
proportion of patients who are alive and free of disease relapse at the end of 2 years
after the start of treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Able to provide written informed consent and can understand and agree to comply with
the requirements of the study and the schedule of assessments
2. Age ≥21 years on the day of signing the ICF
3. ECOG Performance Status ≤1
4. Females of childbearing potential must be willing to use a highly effective method
of birth control for the duration of the study, and ≥120 days after the last dose of
tislelizumab, and have a negative urine or serum pregnancy test ≤7 days of start of
trial
5. Non-sterile males must be willing to use a highly effective method of birth control
for the duration of the study and for ≥120 days after the last dose of tislelizumab
Exclusion Criteria:
1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor
(e.g., CTLA-4, OX 40, CD137)
2. Has received any prior radiotherapy (RT) or systemic anti-cancer therapy including
investigational agents for NPC
3. Any known central nervous system metastases and/or carcinomatous meningitis
4. Active autoimmune diseases or history of autoimmune diseases that may relapse
Note: Patients with the following diseases are not excluded and may proceed to
further screening:
1. Controlled Type I diabetes
2. Hypothyroidism (provided it is managed with hormone replacement therapy only)
3. Controlled celiac disease
4. Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis,
alopecia)
5. Any other disease that is not expected to recur in the absence of external
triggering factors
5. 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)
6. Any condition that required systemic treatment with either corticosteroids (>10 mg
daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days
before start of study
Note: Patients who are currently or have previously been on any of the following
steroid regimens are not excluded:
1. Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent)
2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with
minimal systemic absorption
3. Short course (≤7 days) of corticosteroid prescribed prophylactically (e.g., for
contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g.,
delayed-type hypersensitivity reaction caused by contact allergen)
7. With uncontrolled diabetes or >Grade 1 laboratory test abnormalities in potassium,
sodium, or corrected calcium despite standard medical management or ≥Grade 3
hypoalbuminemia ≤14 days before start of study
8. With history of interstitial lung disease, non-infectious pneumonitis or
uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
9. With severe chronic or active infections requiring systemic antibacterial,
antifungal or antiviral therapy, including tuberculosis infection, etc.
1. Severe infections within 4 weeks before start of study, including but not
limited to hospitalization for complications of infection, bactiraemia, or
severe pneumonia.
2. Received therapeutic oral or intravenous antibiotics within 2 weeks before
start of study.
10. A known history of HIV infection
11. 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
12. Any major surgical procedure requiring general anaesthesia ≤28 days before start of
study
13. Prior allogeneic stem cell transplantation or organ transplantation
14. Any of the following cardiovascular risk factors:
1. Cardiac chest pain, defined as moderate pain that limits instrumental
activities of daily living, ≤28 days before start of study
2. Pulmonary embolism ≤28 days before start of study
3. Any history of acute myocardial infarction ≤6 months before start of study
4. Any history of heart failure meeting New York Heart Association (NYHA)
Classification III or IV ≤6 months before start of study
5. Any event of ventricular arrhythmia ≥Grade 2 in severity ≤6 months before start
of study
6. Any history of cerebrovascular accident ≤6 months before start of study
7. Uncontrolled hypertension: systolic pressure ≥160 mmHg or diastolic pressure
≥100 mmHg despite anti-hypertension medications ≤28 days before start of study
8. Any episode of syncope or seizure ≤28 days before start of study
15. A history of severe hypersensitivity reactions to tislelizumab, gemcitabine,
cisplatin, capecitabine and/or any of its excipients
16. Has received any herbal medicine used to control cancer within 14 days of the start
of study
17. Patients with toxicities (as a result of prior anticancer therapy) which have not
recovered to baseline or stabilized, except for AEs not considered a likely safety
risk (e.g., alopecia, neuropathy and specific laboratory abnormalities)
18. Was administered a live vaccine ≤4 weeks before start of study Note: Seasonal
vaccines for influenza are generally inactivated vaccines and are allowed.
Intranasal vaccines are live vaccines, and are not allowed
19. Underlying medical conditions (including laboratory abnormalities) or alcohol or
drug abuse or dependence that, will be unfavourable for the administration of study
drug or affect the explanation of drug toxicity or AEs or result in insufficient or
might impair compliance with study conduct
20. Concurrent participation in another therapeutic clinical study
Gender:
All
Minimum age:
21 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Centre Singapore
Address:
City:
Singapore
Zip:
168583
Country:
Singapore
Status:
Recruiting
Facility:
Name:
Tan Tock Seng Hospital
Address:
City:
Singapore
Zip:
308433
Country:
Singapore
Status:
Not yet recruiting
Start date:
July 3, 2024
Completion date:
October 2029
Lead sponsor:
Agency:
National Cancer Centre, Singapore
Agency class:
Other
Collaborator:
Agency:
BeiGene
Agency class:
Industry
Collaborator:
Agency:
Tan Tock Seng Hospital
Agency class:
Other
Source:
National Cancer Centre, Singapore
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06093061
