NCT05151588

Induction Chemotherapy and Tazemetostat for Locally Advanced SMARCB1-deficient Sinonasal Carcinoma

A Phase II Single-arm Study of Tazemetostat With Docetaxel, Cisplatin, and 5-fluorouracil as Preoperative Treatment for Locally Advanced Potentially Resectable SMARCB1 (INI-1)- Deficient Sinonasal Carcinoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Dr. Victor H.F. Lee · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

SMARCB1-deficient sinonasal carcinoma is very locally advanced malignancy at diagnosis which often precluded upfront radical resection. The investigators are now proposing a phase II single-arm study on tazemetostat in combination with docetaxel, cisplatin and 5-FU (known as TPF regimen) as preoperative therapy for locally advanced non-metastatic SMARCB1 (INI-1)-deficient sinonasal carcinoma, followed by radical resection and/or post-operative radiation therapy (with or without concurrent chemotherapy), and tazemetostat for another 6 months. It is hypothesized that addition of tazemetostat will improve objective response rate, resectability rate, orbit preservation rate after surgery, and hopefully survival outcomes with manageable safety profiles.

Detailed description

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare but locally aggressive malignancy of the nasal cavity and paranasal sinuses, representing about only 1 % of all head and neck malignancies. It is characterized by loss of INI-1 in the tumour cells under immunohistochemical staining. The overwhelming majority of INI-1 deficient sinonasal carcinoma presents very late at diagnosis, owing to its very similar clinical presentation to other benign conditions like allergic rhinitis, nasal polyps, chronic sinusitis, and some more common malignancies like human papilloma virus-associated squamous cell carcinoma, extranodal NK/T cells lymphoma, mucosal melanoma. Therefore, complete surgical removal remains very challenging and most of the time impossible. Currently, aggressive multimodality treatment of INI-1-deficient sinonasal carcinomas is based on experience with other sinonasal malignancies including case series of sinonasal undifferentiated carcinoma. Upfront surgical resection for potentially resectable cases, followed by adjuvant radiation therapy or adjuvant chemoradiation. Also under investigation is the use of induction chemotherapy followed by surgery and adjuvant radiation in the treatment of sinonasal malignancy. In view of the above, the investigators are now proposing a phase II single-arm study on tazemetostat in combination with TPF as preoperative therapy for locally advanced non-metastatic SMARCB1 (INI-1)-deficient sinonasal carcinoma, followed by radical resection and/or post-operative radiation therapy (with or without concurrent chemotherapy), and tazemetostat for another 6 months. It is hypothesized that addition of tazemetostat will improve objective response rate, resectability rate, orbit preservation rate, and hopefully survival outcomes with manageable safety profiles.

Conditions

• Sinonasal Carcinoma

Interventions

Type	Name	Description
DRUG	Docetaxel	Docetaxel 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy
DRUG	Cis Platinum	Cisplatin 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy
DRUG	5-FU	5-FU 750mg/m2 intravenous infusion from day 1 to day 5 every 3 weeks for 3 cycles as induction therapy
DRUG	Tazemetostat	Tazemetostat 800mg twice per day orally in continuously for 3 cycles as induction therapy and maintenance therapy
PROCEDURE	Surgery	Radical surgery
OTHER	Chemoradiation	Chemoradiation as either radical treatment or post-operative treatment after surgery

Timeline

• Start date: 2023-09-01
• Primary completion: 2026-08-31
• Completion: 2027-08-31
• First posted: 2021-12-09
• Last updated: 2023-02-28