NCT07129772

Perioperative Chemotherapy and Immunotherapy for Locally Recurrent Nasopharyngeal Carcinoma

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)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Sponsor: The University of Hong Kong · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Nasopharyngeal Cancer Recurrent
• Nasopharyngeal Cancinoma (NPC)

Interventions

Type	Name	Description
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

Timeline

• Start date: 2025-11-01
• Primary completion: 2027-12-31
• Completion: 2028-06-30
• First posted: 2025-08-19
• Last updated: 2025-09-04

Locations

1 site across 1 country: Hong Kong