Nasopharyngeal CancerPhase 2NCT05305131
Randomised Trial of Induction Gemcitabine and Cisplatin Versus Gemcitabine, Cisplatin, Pembrolizumab and Bevacizumab (GPPB) in Nasopharyngeal Cancer
A Phase 2 study testing cisplatin and gemcitabine and induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab. in people with Nasopharyngeal Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 months to 99 years
- Conditions the study is for
- Nasopharyngeal Cancer
- What is being tested?
- cisplatin and gemcitabine and induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteSingapore
- Study dates
- 28 Mar 2022to 28 Dec 2026
- 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 21 months to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization/allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
- Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Has received a live vaccine within 30 days of prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine.
- Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
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 University Hospital
Singapore
Wan Qin Chong, MBBS, MRCP, MMed, 6772 4614, wan_qin_chong@nuhs.edu.sg
Wan Qin Chong
About this study
Official title: Phase II Randomised Trial of Induction Gemcitabine and Cisplatin Versus Gemcitabine, Cisplatin, Pembrolizumab and Bevacizumab (GPPB) in Nasopharyngeal Cancer
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)
Read the detailed description
NPC is endemic in Singapore and southern China, where the southern Chinese have the highest incidence of NPC worldwide.
Nasopharyngeal cancer usually presents as locally advanced stage III or IV disease with T3-4 or N2-3 nodal status.The standard of care of patients with locally advanced NPC is concurrent cisplatin chemotherapy with radiation therapy. However, a significant proportion of patients (about 30% in most randomised phase III studies) still relapse, compromising their survival from NPC. This is particularly so in patients with stage IVA, T4 or N3 NPC. Emerging evidence suggests induction chemotherapy improves patient survival in this group of patients when integrated with concurrent chemoradiation. A meta-analysis also showed that the addition of induction chemotherapy improved overall survival, and reduced locoregional and distant failure.
Dysregulation of the vascular endothelial growth factor (VEGF)/VEGF receptor-2 axis is a feature of many cancers including NPC. Elevated VEGF expression promotes disorganised tumour neovascularisation with hyperpermeable, tortuous capillaries.9, 10 Leakiness of vessels increases interstitial fluid pressure that collapses vessels with the collective effect of compromising blood flow and perfusion, limiting the delivery of therapeutic drugs. Furthermore, tumour expression of VEGF promotes immune tolerance directly and through hypoxic mechanisms.11 The VEGF/VEGFR-2 axis can be inhibited humanised monoclonal antibody bevacizumab, which binds to VEGF-A and prevents ligand-receptor engagement.
As NPC is associated with EBV antigen expression and is characterised by a prominent inflammatory infiltrate (inflammatory immune phenotype), there has been great interest in studying the effect of immune checkpoint inhibitors in NPC. Recently, the addition of 2 antiPD1 monoclonal antibodies, toripalimab 12 and camrelizumab 13, to cisplatin and gemcitabine was studied in 2 phase III trials conducted in mainland China. Both studies demonstrated that addition of antiPD1 therapy to cisplatin/gemcitabine chemotherapy improved the response rate, PFS and the duration of response in treatment naïve patients with metastatic or recurrent NPC.
The investigators have conducted a prior study evaluating pembrolizumab with and without bevacizumab. Preliminary analysis showed a higher response rate for addition of bevacizumab to pembrolizumab compared to pembrolizumab alone arm with no new safety signal. Importantly, the adverse effects of anti-angiogenic and anti PD1 therapy in humans are non-overlapping with cytotoxic chemotherapy. In view of this, investigators are conducting an open label, phase II randomised controlled trial comparing induction cisplatin, gemcitabine, bevacizumab and pembrolizumab with the standard arm (induction cisplatin and gemcitabine) in patients with stage III-IVA locally advanced EBER positive nasopharyngeal carcinoma.
- Conditions
- Nasopharyngeal Cancer
- Being tested
- cisplatin and gemcitabine, induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.
- Keywords
- gemcitabine, cisplatin, pembrolizumab, bevacizumab, GPPB
- Medical subject headings
- Nasopharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cisplatin and gemcitabineDrug
Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab. |
What is being measured
The primary outcome is the main question the study is designed to answer.
metabolic complete response assessed using FDG PET whole body scan at 12 weeks of assessment using PERCIST 1.0
Measured: up to 3 years
Secondary outcomes (5)
Number of participant with treatment related toxicities
Safety of induction cisplatin, gemcitabine, pembrolizumab and bevacizumab, compared to induction cisplatin and gemcitabine, using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: up to 3 years
Best objective response rate (ORR) as assessed using Response Evaluation Criteria in Solid Tumour (RECIST 1.1)
Measured: up to 3 years
Disease free survival (DFS) of patients as defined as the time from initiation of treatment to disease recurrence, or death.
Measured: up to 3 years
Overall survival of patients, as defined as the time from initiation of treatment to death.
Measured: up to 3 years
Plasma EBV DNA levels and correlation with clinical response to induction treatment
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2022
- Study start28 Mar 2022
- Primary completion28 Dec 2025 (estimated)
- Study completion28 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Nasopharyngeal CancerStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05305131
- Sponsor's protocol ID
- NP01/04/21
- Status last verified
- Mar 2025
- First submitted
- 22 Mar 2022
- Last updated
- 23 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002 Dec;12(6):421-9. doi: 10.1016/s1044579x02000858.
PubMed 12450728Petersson F. Nasopharyngeal carcinoma: a review. Semin Diagn Pathol. 2015 Jan;32(1):54-73. doi: 10.1053/j.semdp.2015.02.021. Epub 2015 Feb 25.
PubMed 25769204Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005 Jun 11-17;365(9476):2041-54. doi: 10.1016/S0140-6736(05)66698-6.
PubMed 15950718Chan KCA, Woo JKS, King A, Zee BCY, Lam WKJ, Chan SL, Chu SWI, Mak C, Tse IOL, Leung SYM, Chan G, Hui EP, Ma BBY, Chiu RWK, Leung SF, van Hasselt AC, Chan ATC, Lo YMD. Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer. N Engl J Med. 2017 Aug 10;377(6):513-522. doi: 10.1056/NEJMoa1701717.
PubMed 28792880Lee AW, Ma BB, Ng WT, Chan AT. Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective. J Clin Oncol. 2015 Oct 10;33(29):3356-64. doi: 10.1200/JCO.2015.60.9347. Epub 2015 Sep 8.
PubMed 26351355Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. doi: 10.1016/S1470-2045(16)30410-7. Epub 2016 Sep 27.
PubMed 27686945Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.
PubMed 31150573Zhang B, Li MM, Chen WH, Zhao JF, Chen WQ, Dong YH, Gong X, Chen QY, Zhang L, Mo XK, Luo XN, Tian J, Zhang SX. Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019 Oct 2;2(10):e1913619. doi: 10.1001/jamanetworkopen.2019.13619.
PubMed 31626318Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2011 Jul;91(3):1071-121. doi: 10.1152/physrev.00038.2010.
PubMed 21742796Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005 Jan 7;307(5706):58-62. doi: 10.1126/science.1104819.
PubMed 15637262Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018 May;15(5):325-340. doi: 10.1038/nrclinonc.2018.29. Epub 2018 Mar 6.
PubMed 29508855Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.
PubMed 34341578Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. doi: 10.1016/S1470-2045(21)00302-8. Epub 2021 Jun 23.
PubMed 34174189
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomised Trial of Induction Gemcitabine and Cisplatin Versus Gemcitabine, Cisplatin, Pembrolizumab and Bevacizumab (GPPB) in Nasopharyngeal Cancer
- ClinicalTrials.gov ID
- NCT05305131
- Acronym / sponsor ID
- NP01/04/21
- Conditions
- Nasopharyngeal Cancer
- Keywords
- gemcitabine, cisplatin, pembrolizumab, bevacizumab, GPPB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 28 Mar 2022 (actual)
- Primary completion
- 28 Dec 2025 (estimated)
- Study completion
- 28 Dec 2026 (estimated)
- First posted
- 31 Mar 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.
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)
Detailed description
NPC is endemic in Singapore and southern China, where the southern Chinese have the highest incidence of NPC worldwide.
Nasopharyngeal cancer usually presents as locally advanced stage III or IV disease with T3-4 or N2-3 nodal status.The standard of care of patients with locally advanced NPC is concurrent cisplatin chemotherapy with radiation therapy. However, a significant proportion of patients (about 30% in most randomised phase III studies) still relapse, compromising their survival from NPC. This is particularly so in patients with stage IVA, T4 or N3 NPC. Emerging evidence suggests induction chemotherapy improves patient survival in this group of patients when integrated with concurrent chemoradiation. A meta-analysis also showed that the addition of induction chemotherapy improved overall survival, and reduced locoregional and distant failure.
Dysregulation of the vascular endothelial growth factor (VEGF)/VEGF receptor-2 axis is a feature of many cancers including NPC. Elevated VEGF expression promotes disorganised tumour neovascularisation with hyperpermeable, tortuous capillaries.9, 10 Leakiness of vessels increases interstitial fluid pressure that collapses vessels with the collective effect of compromising blood flow and perfusion, limiting the delivery of therapeutic drugs. Furthermore, tumour expression of VEGF promotes immune tolerance directly and through hypoxic mechanisms.11 The VEGF/VEGFR-2 axis can be inhibited humanised monoclonal antibody bevacizumab, which binds to VEGF-A and prevents ligand-receptor engagement.
As NPC is associated with EBV antigen expression and is characterised by a prominent inflammatory infiltrate (inflammatory immune phenotype), there has been great interest in studying the effect of immune checkpoint inhibitors in NPC. Recently, the addition of 2 antiPD1 monoclonal antibodies, toripalimab 12 and camrelizumab 13, to cisplatin and gemcitabine was studied in 2 phase III trials conducted in mainland China. Both studies demonstrated that addition of antiPD1 therapy to cisplatin/gemcitabine chemotherapy improved the response rate, PFS and the duration of response in treatment naïve patients with metastatic or recurrent NPC.
The investigators have conducted a prior study evaluating pembrolizumab with and without bevacizumab. Preliminary analysis showed a higher response rate for addition of bevacizumab to pembrolizumab compared to pembrolizumab alone arm with no new safety signal. Importantly, the adverse effects of anti-angiogenic and anti PD1 therapy in humans are non-overlapping with cytotoxic chemotherapy. In view of this, investigators are conducting an open label, phase II randomised controlled trial comparing induction cisplatin, gemcitabine, bevacizumab and pembrolizumab with the standard arm (induction cisplatin and gemcitabine) in patients with stage III-IVA locally advanced EBER positive nasopharyngeal carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Induction cisplatin and gemcitabine | Experimental | Drug: cisplatin and gemcitabineEach 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. |
| induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab | Experimental | Drug: induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.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. |
Who may qualify
- Ages
- 21 months to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
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 |
|---|---|---|
| cisplatin and gemcitabineDay 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 | Drug | Induction cisplatin and gemcitabine |
| induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab.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 | Drug | induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab |
Primary outcome
metabolic complete response assessed using FDG PET whole body scan at 12 weeks of assessment using PERCIST 1.0
Time frame: up to 3 years
5 secondary outcomes
Number of participant with treatment related toxicities
Time frame: up to 3 years
Best objective response rate (ORR) as assessed using Response Evaluation Criteria in Solid Tumour (RECIST 1.1)
Time frame: up to 3 years
Disease free survival (DFS) of patients as defined as the time from initiation of treatment to disease recurrence, or death.
Time frame: up to 3 years
Overall survival of patients, as defined as the time from initiation of treatment to death.
Time frame: up to 3 years
Plasma EBV DNA levels and correlation with clinical response to induction treatment
Time frame: up to 3 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 23 Sep 2025.
- Background: PubMed 12450728Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002 Dec;12(6):421-9. doi: 10.1016/s1044579x02000858.
- Background: PubMed 25769204Petersson F. Nasopharyngeal carcinoma: a review. Semin Diagn Pathol. 2015 Jan;32(1):54-73. doi: 10.1053/j.semdp.2015.02.021. Epub 2015 Feb 25.
- Background: PubMed 15950718Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005 Jun 11-17;365(9476):2041-54. doi: 10.1016/S0140-6736(05)66698-6.
- Background: PubMed 28792880Chan KCA, Woo JKS, King A, Zee BCY, Lam WKJ, Chan SL, Chu SWI, Mak C, Tse IOL, Leung SYM, Chan G, Hui EP, Ma BBY, Chiu RWK, Leung SF, van Hasselt AC, Chan ATC, Lo YMD. Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer. N Engl J Med. 2017 Aug 10;377(6):513-522. doi: 10.1056/NEJMoa1701717.
- Background: PubMed 26351355Lee AW, Ma BB, Ng WT, Chan AT. Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective. J Clin Oncol. 2015 Oct 10;33(29):3356-64. doi: 10.1200/JCO.2015.60.9347. Epub 2015 Sep 8.
- Background: PubMed 27686945Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. doi: 10.1016/S1470-2045(16)30410-7. Epub 2016 Sep 27.
- Background: PubMed 31150573Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.
- Background: PubMed 31626318Zhang B, Li MM, Chen WH, Zhao JF, Chen WQ, Dong YH, Gong X, Chen QY, Zhang L, Mo XK, Luo XN, Tian J, Zhang SX. Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019 Oct 2;2(10):e1913619. doi: 10.1001/jamanetworkopen.2019.13619.
- Background: PubMed 21742796Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2011 Jul;91(3):1071-121. doi: 10.1152/physrev.00038.2010.
- Background: PubMed 15637262Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005 Jan 7;307(5706):58-62. doi: 10.1126/science.1104819.
- Background: PubMed 29508855Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018 May;15(5):325-340. doi: 10.1038/nrclinonc.2018.29. Epub 2018 Mar 6.
- Background: PubMed 34341578Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. doi: 10.1038/s41591-021-01444-0. Epub 2021 Aug 2.
- Individual participant dataSharing planned: No
Related trials for Nasopharyngeal Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 2
Testing the Addition of BMS-986016 (Relatlimab) to the Usual Immunotherapy After Initial Treatment for Recurrent or Metastatic Nasopharyngeal Cancer
Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma
Active, not recruitingPhase 1
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
Breast Cancer, Ovarian Cancer
Not yet recruitingObservational study
Development and Validation of a Biopsy Decision Model for Nasopharyngeal Carcinoma Based on Serological Markers and Endoscopic Features
Nasopharyngeal Carcinoma (NPC)
RecruitingPhase 1/2
VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma
Head and Neck Carcinoma, Adenoid Cystic Carcinoma
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.
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 cisplatin and gemcitabine and induction chemotherapy cisplatin, gemcitabine, bevacizumab and pembrolizumab. in people with Nasopharyngeal Cancer, run by National University Hospital, 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 14 inclusion and 24 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 23 Sep 2025. 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.
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 Wan Qin Chong, MBBS, MRCP, M Med (6772 4614, wan_qin_chong@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
metabolic complete response assessed using FDG PET whole body scan at 12 weeks of assessment using PERCIST 1.0 (time frame: up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05305131, which also lists 13 linked publications.
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 23 Sep 2025.