Sinonasal CarcinomaPhase 2NCT05151588
Induction Chemotherapy and Tazemetostat for Locally Advanced SMARCB1-deficient Sinonasal Carcinoma
A Phase 2 study testing Docetaxel, Cis Platinum and 5-FU in people with Sinonasal Carcinoma, run by Dr. Victor H.F. Lee.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sinonasal Carcinoma
- What is being tested?
- Docetaxel, Cis Platinum and 5-FU
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2023to 31 Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Have measurable disease as defined by RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
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- Must have a life expectancy of at least 12 weeks before enrollment.
- Time between prior anticancer therapy and first dose of tazemetostat as follows:
- Cytotoxic chemotherapy - At least 21 days Noncytotoxic chemotherapy (e.g., small molecule inhibitor) - At least 14 days. Nitrosoureas - At least 6 weeks. Monoclonal antibody - At least 28 days.
- Adequate haematological functions at baseline before commencement of study medication as defined below:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/liter without growth factor support (filgrastim or pegfilgrastim) for at least 14 days; and ii. Platelets ≥ 100 × 10^9/liter evaluated at least 7 days after platelet transfusion; and iii. Hemoglobin ≥ 9.0 x 10 /litre with blood transfusion allowed before study entry; and after treatment commencement
- Adequate liver function as defined at baseline before commencement of study medication below:
- Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) (except for unconjugated hyperbilirubinemia of Gilbert's syndrome) Alkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
- Adequate renal function as defined below:
- Creatinine < 2.0 or calculated creatinine clearance ≥ 35 mL/minute per the Cockcroft and Gault formula
- For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to the start of treatment. Women will be considered postmenopausal if they are amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- i.) Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). ii.) Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and partner) to use a highly effective form(s) of contraception that results in a low failure rate (<1% per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire program period, and six months for female and at least three months for male patients after taking the last dose of tazemetostat.
Who cannot join
- 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.
- Confirm pregnant or breastfeeding.
- Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
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- On investigational therapy within 21 days at time of recruitment.
- Uncontrolled central nervous system (CNS) metastases requiring steroids.
- On medications that are known potent CYP3A4 inducers/inhibitors (including St. John's wort)
- Unwilling to exclude Seville oranges, grapefruit juice, and grapefruit from their diet.
- Had major surgery within 4 weeks before the first dose of study drug. Note: Minor surgery (e.g., minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 1 week prior to enrollment.
- Unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.
- Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II (Appendix 3), uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia.
- Have an active infection requiring systemic therapy.
- Known hypersensitivity to any component of tazemetostat.
- Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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
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.
Read the 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
- Keywords
- Induction therapy, Chemotherapy, Surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Also called Taxotere
Docetaxel 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy
Cis PlatinumDrug
Also called CDDP
Cisplatin 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy
5-FUDrug
Also called 5-fluorouracil
5-FU 750mg/m2 intravenous infusion from day 1 to day 5 every 3 weeks for 3 cycles as induction therapy
TazemetostatDrug
Also called TAZVERIK
Tazemetostat 800mg twice per day orally in continuously for 3 cycles as induction therapy and maintenance therapy
SurgeryProcedure or surgery
Also called Resection
Radical surgery
ChemoradiationOther
Also called Chemoradiotherapy
Chemoradiation as either radical treatment or post-operative treatment after surgery
| Study group | Role | What they receive |
|---|---|---|
| Induction therapy followed by surgery and postoperative therapy | Experimental | Induction chemotherapy with docetaxel 75mg/m2 on day 1, cisplatin 75mg/m2 on day 1, 5-FU 750mg from day 1 to day 5, given every 3 weeks for 3 cycles and tazemetostat 800mg twice daily orally for 3 cycles, followed by radical surgery or radical chemoradiation, and maintenance tazemetostat 800mg twice daily orally for 6 months Receives: Drug: Docetaxel; Drug: Cis Platinum; Drug: 5-FU; Drug: Tazemetostat; Procedure: Surgery; Other: Chemoradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best objective response
Best objective response
Measured: 48 months
R0 resection rate
R0 resection rate
Measured: 48 months
Secondary outcomes (6)
R1 resection rate
R1 resection rate
Measured: 48 months
Complete pathological response rate
Complete pathological response rate
Measured: 48 months
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
Measured: 48 months
Progression-free survival
Progression-free survival
Measured: 48 months
Overall survival
Overall survival
Measured: 48 months
Incidence of treatment-related side effects
Incidence of treatment-related side effects as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2021
- Study start1 Sep 2023 (estimated)
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sinonasal CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Induction treatment with docetaxel, cisplatin, 5-FU and tazemetostat followed by surgery or radical chemoradiation and maintenance tazemetostat
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr. Victor H.F. Lee
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Victor H.F. Lee, The University of Hong Kong
- Investigators
- Victor Ho Fun Lee, MD, Principal investigator, Department of Clinical Oncology, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05151588
- Sponsor's protocol ID
- SMART-PNS
- Status last verified
- Feb 2023
- First submitted
- 27 Nov 2021
- Last updated
- 28 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make individual participant data (IPD) available to other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05151588
- Acronym / sponsor ID
- SMART-PNS
- Conditions
- Sinonasal Carcinoma
- Keywords
- Induction therapy, Chemotherapy, Surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Dr. Victor H.F. LeeUniversity, hospital or other
- Study start
- 1 Sep 2023 (estimated)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 9 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Induction treatment with docetaxel, cisplatin, 5-FU and tazemetostat followed by surgery or radical chemoradiation and maintenance tazemetostat
| Arm | Type | Receives |
|---|---|---|
| Induction therapy followed by surgery and postoperative therapy | Experimental | Drug: Docetaxel, Drug: Cis Platinum, Drug: 5-FU, Drug: Tazemetostat, Procedure: Surgery, Other: ChemoradiationInduction chemotherapy with docetaxel 75mg/m2 on day 1, cisplatin 75mg/m2 on day 1, 5-FU 750mg from day 1 to day 5, given every 3 weeks for 3 cycles and tazemetostat 800mg twice daily orally for 3 cycles, followed by radical surgery or radical chemoradiation, and maintenance tazemetostat 800mg twice daily orally for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
- Have measurable disease as defined by RECIST 1.1.
Key exclusion criteria (16 listed)
- 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.
- Confirm pregnant or breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DocetaxelAlso: TaxotereDocetaxel 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy | Drug | Induction therapy followed by surgery and postoperative therapy |
| Cis PlatinumAlso: CDDPCisplatin 75mg/m2 intravenous infusion on day 1 every 3 weeks for 3 cycles as induction therapy | Drug | Induction therapy followed by surgery and postoperative therapy |
| 5-FUAlso: 5-fluorouracil5-FU 750mg/m2 intravenous infusion from day 1 to day 5 every 3 weeks for 3 cycles as induction therapy | Drug | Induction therapy followed by surgery and postoperative therapy |
| TazemetostatAlso: TAZVERIKTazemetostat 800mg twice per day orally in continuously for 3 cycles as induction therapy and maintenance therapy | Drug | Induction therapy followed by surgery and postoperative therapy |
| SurgeryAlso: ResectionRadical surgery | Procedure or surgery | Induction therapy followed by surgery and postoperative therapy |
| ChemoradiationAlso: ChemoradiotherapyChemoradiation as either radical treatment or post-operative treatment after surgery | Other | Induction therapy followed by surgery and postoperative therapy |
Primary outcome
Best objective response
Time frame: 48 months
Best objective response
R0 resection rate
Time frame: 48 months
R0 resection rate
6 secondary outcomes
R1 resection rate
Time frame: 48 months
Complete pathological response rate
Time frame: 48 months
Orbit preservation rate
Time frame: 48 months
Progression-free survival
Time frame: 48 months
Overall survival
Time frame: 48 months
Incidence of treatment-related side effects
Time frame: 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Individual participant dataSharing planned: No. There is no plan to make individual participant data (IPD) available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Victor Ho Fun Lee, MD principal investigator
Department of Clinical Oncology, The University of Hong Kong
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel, Cis Platinum and 5-FU in people with Sinonasal Carcinoma, run by Dr. Victor H.F. Lee.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Victor Ho Fun Lee, MD (852-2255-4352, vhflee@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best objective response (time frame: 48 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2023.