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Nasopharyngeal Cancer RecurrentPhase 2NCT07129772

Perioperative Chemotherapy and Immunotherapy for Locally Recurrent Nasopharyngeal Carcinoma

A Phase 2 study testing Gemcitabine (GEM), Cisplatin and PEMBROLIZUMAB (alone or when added to a regimen above) in people with Nasopharyngeal Cancer Recurrent and Nasopharyngeal Cancinoma (NPC), run by The University of Hong Kong at 1 site in Hong Kong.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southern China and southeast Asia. Despite intensive radical therapy, between 15% and 30% of NPC patients develop relapse. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gemcitabine (GEM), Cisplatin and PEMBROLIZUMAB (alone or when added to a regimen above)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteHong Kong
Study dates
1 Nov 2025to 30 Jun 2028
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of histologically confirmed locally recurrent (rT2-T4, N0-N1, M0) NPC (undifferentiated carcinoma with Epstein-Barr virus (EBV) infection by either presence of Epstein-Barr virus encoded RNA (EBER) in in-situ hybridization of the recently obtained tumor specimen before study entry) or an elevation of plasma EBV DNA in the subject's peripheral blood), staged according to the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging classification (TNM-8). All patients should NOT have received any form of anti-tumor treatment for their locally recurrent NPC before joining the study. However, prior radical treatment for their NPC at diagnosis is allowed if there is at least a 6-month interval between prior radical treatment and the start of study intervention of this study.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Aged ≥18 years old
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
  • All eligible patients must be magnetic resonance imaging of T1, T2 and T1-contrast enhanced sequences of the head and neck region and PET-CT scan within 30 days of study entry.
  • Modified Charlson Comorbidity Score <2
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  • Adult Comorbidity Evaluation (ACE)-27 Index <2
  • Pre-existing peripheral neuropathy <=1
  • Have adequate organ function as defined in the following table (Table 5.1.1).
  • Body Weight >30kg
  • For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to the start of treatment for their NPC. Women will be considered postmenopausal if they are amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: - Women 1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Must have a life expectancy of at least 12 weeks.

Who cannot join

  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter.
  • Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has had any prior monoclonal antibody before study entry, including but not limited to anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another costimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137 etc).
  • Has had prior chemotherapy or targeted small molecule therapy (including sorafenib or other anti-vascular endothelial growth factor inhibitor) before study entry. Patients who received radical radiation therapy and chemotherapy (but not immune checkpoint inhibitors or any form of immunotherapy) for their previously untreated nasopharyngeal carcinoma at diagnosis was allowed to join this study, provided that such radical treatment was completed >6 months before study entry.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Other exceptions may be considered with Sponsor consultation.
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  • Note: Participants with low risk early-stage prostate cancer defined as below are not excluded: Stage T1c or T2a with a Gleason score ≤6 and a prostate-specific antigen (≤10 ng/ml) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation.
  • Has known carcinomatous meningitis (also known as leptomeningeal carcinomatosis).
  • Has an active infection requiring intravenous systemic therapy or hospital admission.
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, 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.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Routine checking for Anti-HIV1 or Anti-HIV2 is not mandatory.
  • Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection.
  • Has received a live vaccine 30 days prior to the first dose of trial treatment.
  • Has experienced Grade 4 toxicity on treatment with prior radiation.
  • Has experienced Grade 3-4 intracranial toxicity (hypophysitis or central nervous system toxicity) with either prior intracranial radiation and/or chemotherapy.
  • Is taking > 4mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required > 4mg/day of dexamethasone or its equivalent for 3 consecutive days within 1 week of starting treatment.
  • Allergies and adverse drug reaction to the following: History of allergy to study drug components; History of severe hypersensitivity reaction to any monoclonal antibody.
  • Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. (a) Patients with Grade >=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. (b) Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with pembrolizumab may be included only after consultation with the Study Physician.
  • Major surgical procedure (as defined by the Investigator within 28 days prior to the first dose of IP. Local surgery of isolated lesions for palliative intent is acceptable.
  • History of allogenic organ transplantation.
  • History of leptomeningeal carcinomatosis.
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >=470ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >=470ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of pembrolizumab. The following are exceptions to this criterion: (a) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) (b) Systemic corticosteroids at physiologic doses not to exceed <> of prednisone or its equivalent (c) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Victor Ho-Fun Lee, MD contact

852-2255-4352

vhflee@hku.hk

Wai-Tak Law, BSc contact

852-2255-5124

rlwt@hku.hk

Hong Kong1 site

  • Department of Clinical Oncology, Queen Mary Hospital

    Hong Kong

Other trials in Hong Kong

About this study

Official title: A Multicenter, Single Arm Phase II Study on Pembrolizumab and Chemotherapy as Perioperative Treatment Followed by Nasopharyngectomy and Maintenance Pembrolizumab for Locally Recurrent Nasopharyngeal Carcinoma (PINNACLE)

Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southern China and southeast Asia. Despite intensive radical therapy, between 15% and 30% of NPC patients develop relapse. Recent phase III randomized-controlled trials conducted in China demonstrated an improvement of progression-free survival with combinational therapy immune checkpoint inhibitors (ICI) (camrelizumab, toripalimab, and tislelizumab, respective) and chemotherapy gemcitabine (G) and cisplatin (P) compared with chemotherapy GP alone for recurrent or metastatic NPC. However, none of these studies have described in details the treatment outcomes of those subjects with locally recurrent NPC only, and whether any of these patients would undergo radical surgery to remove the residual locally recurrent NPC after ICI and chemotherapy. Continuation of the same ICI as maintenance therapy may only be the treatment option for these patients who were recruited into these phase III trials, unless if they withdrew from the study and opted for radical resection. While continuing the same ICI may still lead to persistent objective response and disease control, there is a possibility of tumor recurrence leading to unresectable disease and a worse survival outcome, or unexpected, rare but recognized immune-related emergent adverse events with ICI. Radical resection after maximal response to ICI and chemotherapy for patients with locally recurrent NPC only may provide a chance of cure of the disease and these patients may be obviated from continuous exposure to ICI therapy.

In view of the above, we are now proposing a phase II single-arm study on perioperative pembrolizumab and chemotherapy followed by radical surgery for locally recurrent NPC. As a collateral study, we will also perform single-cell DNA and RNA sequencing and proteomics study to observe the tumor and immune microenvironment which certainly helps us decipher the mechanisms of tumor response at genomic, transcriptomic and proteomic levels.

Read the detailed description

This is a multi-centre single-arm phase II study on perioperative treatment with pembrolizumab and chemotherapy GP for 6 cycles followed by radical surgery and maintenance pembrolizumab for another 11 cycles (up to 17 cycles of pembrolizumab in total).

All eligible patients shall receive preoperative treatment with pembrolizumab at 200mg fixed dose, with chemotherapy G: 1000-1250mg/m2 on day 1 and day 8 and P: 80-100mg/m2 on day 1 (or carboplatin AUC=5 on day 1 replacing cisplatin at the treating physician's discretion), given every 3 weeks for 6 cycles followed by radical surgery (open or minimally invasive surgery) at the discretion of treating surgeons, and subsequently maintenance pembrolizumab for another 11 cycles (up to 17 cycles of pembrolizumab for 1 year).

All recruited patients will undergo reassesment imaging scans after 3 and 6 cycles of pembrolizumab and chemotherapy GP. They will then undergo radical surgery within 4 to 6 weeks of the 6th cycle of pembrolizumab and chemotherapy GP. Subsequently, within 4 to 6 weeks of radical surgery, they will continue the remaining 11 cycles of pembrolizumab 200mg fixed dose every 3 weeks up to 17 cycles in total.

Magnetic resonance imaging (MRI) of the head and neck and positron emission tomography with integrated computed tomography (PET-CT) scan will be performed at baseline before study intervention and after 3 and 6 cycles of pembrolizumab and chemotherapy GP and before radical surgery, to evaluate tumor response. After radical surgery, all recruited subjects will undergo repeat MRI and contrast-enhanced computed tomography (CT) scan of the thorax and abdomen every 3 months during the 1st year, then every 4 months during the 2nd year, every 6 months during the 3rd and 4th year, and yearly from the 5th year onwards.

Being tested
Gemcitabine (GEM), Cisplatin, PEMBROLIZUMAB (alone or when added to a regimen above)
Keywords
Nasopharyngeal carcinoma, Locally recurrent, Perioperative treatment, Immune checkpoint inhibitor, Chemotherapy, Minimally invasive surgery
Medical subject headings
Nasopharyngeal Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gemcitabine (GEM)Drug

    Also called Gemcitabine

    Gemcitabine, cisplatin and pembrolizumab for up to 6 cycles followed by minimally invasive surgery (either endoscopic nasopharyngectomy or transoral robotic-assisted nasopharyngectomy) and maintenance pembrolizumab for a total of 1 year for locally recurrent nasopharyngeal carcinoma

  • CisplatinDrug

    Gemcitabine, cisplatin and pembrolizumab for up to 6 cycles followed by minimally invasive surgery (either endoscopic nasopharyngectomy or transoral robotic-assisted nasopharyngectomy) and maintenance pembrolizumab for a total of 1 year for locally recurrent nasopharyngeal carcinoma

  • PEMBROLIZUMAB (alone or when added to a regimen above)Drug

    Also called Keytruda

    Gemcitabine, cisplatin and pembrolizumab for up to 6 cycles followed by minimally invasive surgery (either endoscopic nasopharyngectomy or transoral robotic-assisted nasopharyngectomy) and maintenance pembrolizumab for a total of 1 year for locally recurrent nasopharyngeal carcinoma

Study groups in NCT07129772
Study groupRoleWhat they receive
Perioperative chemotherapy and immune checkpoint inhibitor for recurrent nasopharyngeal carcinomaExperimentalPerioperative chemotherapy and immune checkpoint inhibitor every 3 weeks for up to 6 cycles followed by radically minimally invasive surgery e.g. endoscopic nasopharyngectomy or transoral robotic-assisted nasopharyngectomy and maintenance pembrolizumab for a total of 1 year for locally recurrent nasopharyngeal carcinoma.
Receives: Drug: Gemcitabine (GEM); Drug: Cisplatin; Drug: PEMBROLIZUMAB (alone or when added to a regimen above)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological complete response rate

    Rate of the absence of all detectable cancer cells in tissue samples examined under a microscope by certified pathologists after perioperative treatment with gemcitabine, cisplatin and pembrolizumab and minimally invasive surgery (either endoscopic nasopharyngectomy or transoral robotic-assisted nasopharyngectomy) for locally recurrent nasopharyngeal carcinoma

    Measured: 36 months

Secondary outcomes (6)

  1. Objective response rate

    Rate of objective response as per RECIST 1.1 or irRECIST

    Measured: 36 months

  2. Major pathological response

    Rate of the less than or equal to 10% of detectable and viable cancer cells in tissue samples examined under a microscope by certified pathologists after perioperative treatment with gemcitabine, cisplatin and pembrolizumab and minimally invasive surgery (either endoscopic nasopharyngectomy or transoral robotic-assisted nasopharyngectomy) for locally recurrent nasopharyngeal carcinoma

    Measured: 36 months

  3. Recurrence-free survival

    Rate of survival calculated from the time of the date of written informed consent to the date of radiologically confirmed recurrence of nasopharyngeal carcinoma or the date of death from any cause

    Measured: 36 months

  4. Overall survival

    Rate of survival calculated from the time of the date of written informed consent to the date of death from any cause

    Measured: 36 months

  5. Toxicity profiles

    Number of participants who suffer from adverse events or serious adverse events according to Common Terminology Criteria for Adverse Events version 5.0

    Measured: 36 months

  6. Biomarkers

    Number of participants found to have biomarkers including tumor and blood biomarkers predictive of objective response to perioperative treatment with gemcitabine, cisplatin and pembrolizumab

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2025
  2. Study start1 Nov 2025 (estimated)
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Model description
Perioperative chemotherapy and immune checkpoint inhibitor for locally recurrent nasopharyngeal carcinoma
Masking
None (open label)
Enrolment
53 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07129772
Sponsor's protocol ID
PINNACLE
Status last verified
Jul 2025
First submitted
11 Aug 2025
Last updated
4 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual patient data of this study will not be shared unless a request with an approved research proposal is submitted to the principal investigator for consideration.

Publications

  • Chan ATC, Lee VHF, Hong RL, Ahn MJ, Chong WQ, Kim SB, Ho GF, Caguioa PB, Ngamphaiboon N, Ho C, Aziz MASA, Ng QS, Yen CJ, Soparattanapaisarn N, Ngan RK, Kho SK, Tiambeng MLA, Yun T, Sriuranpong V, Algazi AP, Cheng A, Massarelli E, Swaby RF, Saraf S, Yuan J, Siu LL. Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial. Ann Oncol. 2023 Mar;34(3):251-261. doi: 10.1016/j.annonc.2022.12.007. Epub 2022 Dec 16.

    PubMed 36535566

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine (GEM), Cisplatin and PEMBROLIZUMAB (alone or when added to a regimen above) in people with Nasopharyngeal Cancer Recurrent and Nasopharyngeal Cancinoma (NPC), run by The University of Hong Kong at 1 site in Hong Kong.

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 13 inclusion and 26 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: opening soon, as of the sponsor's last update on 4 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 Hong Kong. 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 Victor Ho-Fun Lee, MD (852-2255-4352, vhflee@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response rate (time frame: 36 months). 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 NCT07129772, which also lists 1 linked publication.

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 4 Sep 2025.

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