Perioperative Chemotherapy and Immunotherapy for Locally Recurrent Nasopharyngeal Carcinoma

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)

Interventions

DRUG

Gemcitabine (GEM)

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

DRUG

Cisplatin

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

DRUG

PEMBROLIZUMAB (alone or when added to a regimen above)

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

Sponsors & Collaborators

• Sun Yat-sen University

  collaborator OTHER

• Changhua Christian Hospital

  collaborator OTHER

• National University of Singapore

  collaborator OTHER

• The University of Hong Kong

  lead OTHER

Principal Investigators

• Victor Ho-Fun Lee, MD · Department of Clinical Oncology, The University of Hong Kong

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-11-01

Primary Completion

2027-12-31

Completion

2028-06-30

Countries

• Hong Kong

Study Locations