Perioperative Chemotherapy and Immunotherapy for Locally Recurrent Nasopharyngeal Carcinoma

NCT07129772 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: PINNACLE
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Nasopharyngeal Cancer Recurrent; Nasopharyngeal Cancinoma (NPC)

Keywords

Nasopharyngeal carcinoma; Locally recurrent; Perioperative treatment; Immune checkpoint inhibitor; Chemotherapy; Minimally invasive surgery

Outcome Measures

Primary Outcomes (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

  36 months

Secondary Outcomes (6)

• Objective response rate

  36 months

• Major pathological response

  36 months

• Recurrence-free survival

  36 months

• Overall survival

  36 months

• Toxicity profiles

  36 months

Study Arms (1)

Perioperative chemotherapy and immune checkpoint inhibitor for recurrent nasopharyngeal carcinoma

EXPERIMENTAL

Perioperative 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.

Drug: Gemcitabine (GEM); Drug: Cisplatin; Drug: PEMBROLIZUMAB (alone or when added to a regimen above)

Interventions

Gemcitabine (GEM) DRUG

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

Also known as: Gemcitabine

Perioperative chemotherapy and immune checkpoint inhibitor for recurrent nasopharyngeal carcinoma

Cisplatin DRUG

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

Perioperative chemotherapy and immune checkpoint inhibitor for recurrent nasopharyngeal carcinoma

PEMBROLIZUMAB (alone or when added to a regimen above) DRUG

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

Also known as: Keytruda

Perioperative chemotherapy and immune checkpoint inhibitor for recurrent nasopharyngeal carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• The University of Hong Kong: lead
• Sun Yat-sen University: collaborator
• Changhua Christian Hospital: collaborator
• National University of Singapore: collaborator

Study Sites (1)

Department of Clinical Oncology, Queen Mary Hospital

Hong Kong, Hong Kong

Location

Related Publications (1)

• 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.

  PMID: 36535566 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Gemcitabine; Cisplatin; pembrolizumab; Single Person

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors

Study Officials

• Victor Ho-Fun Lee, MD

  Department of Clinical Oncology, The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Victor Ho-Fun Lee, MD

CONTACT

852-2255-4352; vhflee@hku.hk

Wai-Tak Law, BSc

CONTACT

852-2255-5124; rlwt@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Inapplicable
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Perioperative chemotherapy and immune checkpoint inhibitor for locally recurrent nasopharyngeal carcinoma

Study Record Dates

• First Submitted: August 11, 2025
• First Posted: August 19, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: September 4, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)