Randomised Trial of Induction Gemcitabine and Cisplatin Versus Gemcitabine, Cisplatin, Pembrolizumab and Bevacizumab (GPPB) in Nasopharyngeal Cancer

NCT05305131 | Recruiting Phase 2

• 1 other identifier: NP01/04/21
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that the addition of bevacizumab and pembrolizumab to induction cisplatin and gemcitabine is tolerable and improves metabolic complete response (mCR), relapse free survival (RFS) and overall survival (OS) compared to induction cisplatin and gemcitabine in patients with locally advanced nasopharyngeal cancer (NPC)

Conditions

Nasopharyngeal Cancer

Keywords

gemcitabine; cisplatin; pembrolizumab; bevacizumab; GPPB

Outcome Measures

Primary Outcomes (1)

• metabolic complete response assessed using FDG PET whole body scan at 12 weeks of assessment using PERCIST 1.0

  up to 3 years

Secondary Outcomes (5)

• Number of participant with treatment related toxicities

  up to 3 years

• Best objective response rate (ORR) as assessed using Response Evaluation Criteria in Solid Tumour (RECIST 1.1)

  up to 3 years

• Disease free survival (DFS) of patients as defined as the time from initiation of treatment to disease recurrence, or death.

  up to 3 years

• Overall survival of patients, as defined as the time from initiation of treatment to death.

  up to 3 years

• Plasma EBV DNA levels and correlation with clinical response to induction treatment

  up to 3 years

Study Arms (2)

Induction cisplatin and gemcitabine

EXPERIMENTAL

Each treatment cycle is 3 weeks. All patients would receive 3 cycles of induction chemotherapy as part of the study, and would then be considered for subsequent concurrent chemoradiotherapy at the investigator's discretion. Cross over is not allowed.

Drug: cisplatin and gemcitabine

induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab

EXPERIMENTAL

Each treatment cycle is 3 weeks. All patients would receive 3 cycles of induction chemotherapy as part of the study, and would then be considered for subsequent concurrent chemoradiotherapy at the investigator's discretion. Cross over is not allowed.

Drug: induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.

Interventions

cisplatin and gemcitabine DRUG

Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2

Induction cisplatin and gemcitabine

induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab. DRUG

Day -7 (+/-1 day): IV bevacizumab 7.5mg/kg diluted in normal saline over 30 minutes Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2+ IV pembrolizumab 200mg over 30 minutes Day 8: IV Gemcitabine 1000mg/m2 Day 15 (for cycles 1 and 2 only): IV bevacizumab 7.5mg/kg diluted in normal saline over 30 minutes

induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab

Eligibility Criteria

• Age: 21 Months - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant (or legally acceptable representative if applicable) provides written consent for the trial.
• Participants who are at least 21 years of age on the day of signing informed consent with histologically or cytologically confirmed diagnosis of non-keratinizing nasopharyngeal carcinoma (NPC).
• Have measurable disease based on RECIST 1.1.
• Tumour stage III (except for T3N0 and T3N1) or IVA according to the American Joint Committee on Cancer (AJCC) 8th edition criteria.
• Have locally or centrally determined EBV-positive NPC by EBV-encoded small RNA in situ hybridization (EBER in situ hybridization \[ISH\]) assay. If EBV-positive status has been previously determined by EBER ISH assay, then no re-testing is required.
• Note: If EBV status by EBER ISH assay has not been previously determined, tumor tissue from archival tissue may be submitted for EBV determination.
• Did not receive any prior treatment
• Willingness to donate blood for mandatory translational research studies.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have an adequate organ function
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 of study protocol OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 of study protocol during the treatment period and for at least 120 days after the last dose of study medication.
• A male participant must agree to use a contraception as detailed in Appendix 3 of study protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.

You may not qualify if:

• Stage III NPC with T3N0 or T3N1 staged by AJCC 8th edition
• Has received prior systemic anti-cancer therapy including chemotherapy, radiotherapy, immunotherapy or investigational agents
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to first dose of study treatment.
• Has a condition requiring systemic steroid therapy (\> 10 mg daily prednisone equivalents) or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. Inhaled or topical steroids and adrenal replacement doses \<10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< or = 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has hypersensitivity to bevacizumab or any of its components.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g. breast or cervical carcinoma in situ) that have undergone potentially curative therapy are not excluded.
• Has an active infection requiring systemic therapy, or serious non-healing wound, ulcer or bone fracture.
• Uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of = 3 anti-hypertensive drugs or systolic blood pressure greater than 150 mmHg).
• History of cardiac disease: congestive heart failure \> New York Heart Association (NYHA) Class II; active coronary artery disease (unstable angina \[anginal symptoms at rest\] or new-onset angina \[began within the last 3 months\] or myocardial infarction within the past 6 months). Cardiac arrhythmias requiring anti-arrhythmic therapy (ß-blockers or digoxin are permitted).
• Persistent proteinuria of NCI-CTCAE Grade 3 or higher (\> 3.5 g/24 hours, measured by urine protein/creatinine ratio on a random urine sample).
• Clinically significant bleeding (NCI-CTCAE Grade 3 or higher) within 30 days prior to start of study medication.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

RECRUITING

Related Publications (13)

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MeSH Terms

Conditions

Nasopharyngeal Neoplasms

Interventions

Cisplatin; Gemcitabine; Bevacizumab; pembrolizumab

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Wan Qin Chong, MBBS, MRCP, M Med

CONTACT

6772 4614; wan_qin_chong@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a single-centre, open label, randomised phase II study of induction cisplatin and gemcitabine with or without bevacizumab in patients with locally advanced or metastatic NPC. 50 Eligible patients will be randomised 1:1 into either of the two study arms: induction chemotherapy cisplatin and gemcitabine, or induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: March 31, 2022
• Study Start: March 28, 2022
• Primary Completion: December 28, 2025
• Study Completion (Estimated): December 28, 2026
• Last Updated: September 23, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)