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.
Males or females are >18 years of age with body weight ≥40kg at the time of providing voluntary written informed consent.
Voluntarily sign the written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF), and undergoing treatment and scheduled visits and examinations including follow up during the study period,
Histologically and/or cytologically confirmed locally advanced (T3-T4bN0-N3M0) non-metastatic SMARCB1 (INI-1)-deficient sinonasal carcinoma
For subjects who have experienced any clinically significant toxicity related to a prior anticancer treatment (i.e., chemotherapy, immunotherapy, and/or radiotherapy): at the time the subject provides voluntary written informed consent, all toxicities have either resolved to grade 1 per NCI CTCAE Version 5.0 OR are clinically stable and no longer clinically significant.
Pre-existing or co-existing epithelioid sarcoma.
Has a prior history of T-Cell lymphoblastic lymphoma, T-cell acute lymphoblastic leukemia, myelodysplastic syndrome, acute myeloid leukemia, or myeloproliferative neoplasm.
Have undergone a solid organ transplant.
Prior malignancy in the past 5 years.
Single group
Docetaxel
DrugDocetaxel 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy
Cis Platinum
DrugCisplatin 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy
5-FU
Drug5-FU 750mg/m2 intravenous infusion from day 1 to day 5 every 3 weeks for 3 cycles as induction therapy
Tazemetostat
DrugTazemetostat 800mg twice per day orally in continuously for 3 cycles as induction therapy and maintenance therapy
Surgery
Procedure/SurgeryRadical surgery
Chemoradiation
Other interventionChemoradiation as either radical treatment or post-operative treatment after surgery
Best objective response
Best objective response
R0 resection rate
R0 resection rate
R1 resection rate
R1 resection rate
Complete pathological response rate
Complete pathological response rate
Orbit preservation rate
Orbit preservation rate defined as the rate that sums up that of orbit preservation surgery with a clear resection and that of radical chemoradiation after induction TPF and tazemetostat
Progression-free survival
Progression-free survival
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Dr. Victor H.F. Lee
Lead sponsor
The University of Hong Kong
Sponsor institution
This trial is not recruiting at the moment. You can still explore other options:
