tReatment Individualisation By EBV stratificatiON in Nasopharyngeal Carcinoma: an Umbrella Platform Study (RIBBON-Umbrella)

NCT05517135 | Recruiting

• 1 other identifier: 2022/2315
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief 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 on-treatment plasma EBV DNA results.

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal Carcinoma; EBV DNA; Biomarker-guided; Treatment Individualization; Risk Stratification

Outcome Measures

Primary Outcomes (1)

• Disease-Free Survival

  2 years from end of treatment

Secondary Outcomes (5)

• Overall survival

  2 years after end of treatment

• Distant metastasis-free survival

  2 years after end of treatment

• Loco-regional recurrence-free survival

  2 years after end of treatment

• Treatment-related adverse events

  From start of treatment to 30 days after last treatment and up to 5 years post - treatment

• Genome sequencing of biological samples

  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

Study Arms (5)

Arm 1

Arm 1: Pre-treatment EBV DNA \<4000 copies/mL AND N0-1 or T4N0 (TNM AJCC/UICC 8th edition)

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)

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

Other: Arm 3

Group 1

Group 1: Recurrent/metastatic NPC, EBV DNA \<4000 copies/mL

Other: Group 1

Group 2

Group 2: Recurrent/metastatic NPC, EBV DNA ≥4000 copies/mL

Other: Group 2

Interventions

Arm 1 OTHER

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 1

Arm 2 OTHER

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 2

Arm 3 OTHER

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: 1. RIBBON-LA-01 (NCT06093061) 2. CCRT + metronomic capecitabine (650 mg/m2 bid oral for 12 months)

Arm 3

Group 1 OTHER

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 1

Group 2 OTHER

Combination chemotherapy (using cisplatin or carboplatin with gemcitabine, 5-fluorouracil or docetaxel) with or without ICB +/- maintenance ICB or capecitabine

Group 2

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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.
• a. 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

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre Singapore

Singapore, 168583, Singapore

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Archival tissue, fresh tumour biopsy tissue, saliva and peripheral blood samples will be obtained for this study

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

DMAC2L protein, human

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Melvin Lee Kiang Chua, MBBS, FRCR, PhD, FAMS

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melvin Lee Kiang Chua, MBBS, FRCR, PhD, FAMS

CONTACT

64368000; melvin.chua.l.k@singhealth.com.sg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: August 26, 2022
• Study Start: November 17, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

SG (1)