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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02099188
Other study ID # SINTART2
Secondary ID 2013-000580-93
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date November 2013
Est. completion date January 2024

Study information

Verified date April 2022
Source Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Sinonasal tumors are rare diseases, as they account for the 0.2 % - 0.8 % of all tumors. For patients with inoperable tumors, the prognosis is poor and the current therapy is a combined-modality treatment that is both more effective and associated with less morbidity. This study proposes innovative integration of multiple modality of treatment modulated by histology, molecular profile and response to induction CT.


Description:

So far, surgery followed by radiotherapy (RT) has been the usual approach for advanced disease. Technical improvements in surgical approaches have been reported, providing less invasive surgery with lower morbidity. However, there are cases of unresectable tumors where the needs of novel strategies is higher. New therapeutic strategies are needed to obtain more efficient treatment with less morbidity. Some studies explored the role and feasibility of induction chemotherapy (CT) and the prognostic value of response to CT. Histology and molecular pattern can guide the type of administered CT. The first drives the choice of drug to be associated with Cisplatin, while mutational status of p53 (wild type, WT vs mutated, MUT) is a predictive value for response to CT with Cisplatin plus 5-Fluorouracil and Leucovorin in ITAC. Moreover, proton/carbon ion beam therapy, compared to conventional photon therapy, provides a more accurate and intense dose to tumor area, with potentially higher control of disease. Treatment outcomes for unresectable paranasal sinus carcinoma are poor, and combined-modality treatment is needed to find out novel therapeutic strategies.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 27
Est. completion date January 2024
Est. primary completion date June 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Signed and dated IEC-approved Informed Consent. 2. Diagnosis of sinonasal tumor with the following histotypes: - Squamous Cell Carcinoma (SCC); - Sinonasal Undifferentiated Carcinoma (SNUC); - Small Cell Carcinoma Neuroendocrine Type (SmCCNET); - Pure Sinonasal Neuroendocrine Carcinoma (SNEC); - Intestinal Type Adenocarcinoma (ITAC) with a functional p53 gene; - Esthesioneuroblastoma with differentiation grade III-IV by Hyams. 3. AJCC stage T4b. 4. Unresectable disease. 5. ECOG performance status 0-2. 6. Adequate bone marrow, renal and hepatic functionality, defined as haemoglobin >10 g/dL, neutrophils >1500/mmc, platelets > 100.000/mmc, creatinine value = 1.5 x ULN or calculated creatinine clearance (by Cockcroft and Gault's formula) > 60 mL/min, transaminases values < 1.5 times over the upper limit of normal (ULN). 7. Polychemotherapy treatment clinical feasibility as per Investigator's Judgment. 8. Male or female patients = 18 years of age. 9. Negative pregnancy test (if female in reproductive years). 10. Agreement upon the use of effective contraceptive methods (hormonal or barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation, if men and women of child producing potential. Exclusion Criteria: 1. Previous radiotherapy or chemotherapy for head and neck district tumors (surgical treatment relapses are admitted). 2. Metastatic disease. 3. Cardiac, pulmonary, infective, neurological disease or any other medical condition that could interfere with treatment. 4. Unable and unwilling to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol. 5. Previous diagnosis of other malignant neoplasm in the last 3 years (in situ cervical cancer or completely excised basocellular/squamocellular skin cancer are always admitted). 6. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Cisplatin
80 mg/m2 or 33 mg/m2/day or 100 mg/m2 - Concentrate for solution for infusion
Docetaxel
75 mg/m2 - Concentrate for solution for infusion
5-fluorouracil
800 mg/m2/day - Concentrate for solution for infusion
Etoposide
150 mg/m2/day - Concentrate for solution for infusion
Adriamycin
20 mg/m2/day - Powder for solution for infusion
Ifosfamide
3000 mg/m2/day - Powder for solution for infusion
Leucovorin
250 mg/m2/day - Powder for solution for infusion
Radiation:
Radiotherapy - Patients needing Elective Nodal Volume (ENI)
LR-PTV: 50.4-54 Gy with 1.8-2 Gy per fraction will be prescribed. This volume will always be treated with photons IMRT. Particle boost with ENI: HR-PTV: carbon ions 18 - 21 Gy (relative biological effectiveness, RBE) in fractions of 3 Gy (RBE) without concomitant chemotherapy IR-PTV: this volume is optional, if used it will receive the first 3 fractions i.e. 9 Gy (RBE) of the boost. Photons boost with ENI. HR-PTV: at least 70 Gy with 2-2.12 Gy per fraction and 66 Gy at 2Gy per fraction in radical setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed.
Radiotherapy - Patients not needing ENI
Treatment with particles. IR-PTV: this volume can be larger or equal to HR-PTV according to individual situations. 50.4-54 Gy with 1.8-2 Gy per fraction will be prescribed to IR-PTV with protontherapy with concomitant chemotherapy. HR-PTV: carbon ions 18 - 21 Gy (RBE) in fractions of 3 Gy (RBE) without concomitant chemotherapy. The first 3 fractions may be given to the bigger IR-PTV. Treatment with photons. HR-PTV: at least 70 Gy with 2-2.12 Gy per fraction and 66 Gy at 2Gy per fraction in radical setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed.
Radiotherapy - Patients needing curative neck irradiation
LR-PTV: 50.4-54 Gy with 1.8-2 Gy per fraction will be prescribed. This volume will always be treated with photons IMRT. Particle boost. HR-PTV: carbon ions 18 - 21 Gy (RBE) in fractions of 3 Gy (RBE) without concomitant chemotherapy IR-PTV: this volume is optional, if used it will receive the first 3 fractions i.e. 9 Gy (RBE) of the boost. Photons boost. HR-PTV: at least 70 Gy with 2-2.12 Gy per fraction and 66 Gy at 2Gy per fraction in radical and postoperative setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed.

Locations

Country Name City State
Italy Presidio Ospedaliero Spedali Civili di Brescia Brescia BS
Italy Fondazione IRCCS Istituto Nazionale Tumori Milano MI
Italy Azienda Ospedaliera "Maggiore della Carità" Novara
Italy IRCCS Policlinico San Matteo Pavia PV
Italy A.O. Ospedale di Circolo e Fondazione Macchi Varese VA

Sponsors (2)

Lead Sponsor Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano Regione Lombardia

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression Free Survival (PFS) Progression Free Survival (PFS) at 5 years, defined as the time from enrollment to progression of disease or death for any cause; last date of follow up will be registered for patients alive not in progression. PFS will be assessed at 5 years.
Secondary Overall survival (OS) Overall survival defined as the time from enrollment (ITT population) or treatment start (PP population) to the date of death from any causes; last date of follow up will be registered for patients alive. Overall survival will be assessed at the following time frames: 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, 60 months, 72 months, 84 months, 96 months.
Secondary Ocular function preservation by visual field tests. Ocular function preservation by visual field tests. At the enrollment. During follow-up after: 3 months, 12 months, 24 months, 36 months, 48 months, 60 months, 72 months, 84 months, 96 months.
Secondary Hearing preservation performed by audiogram test. Hearing preservation performed by audiogram test. At the enrollment. During follow-up after: 3 months, 12 months, 24 months, 36 months, 48 months, 60 months, 72 months, 84 months, 96 months.
Secondary Overall safety profile of the whole treatment. Overall safety profile of the whole treatment characterized by type, severity graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.03), timing and relationship to study therapy of adverse events and laboratory abnormalities collected. From the day of the Informed Consent Form signature through to 90 days after the last dose of the last therapy administered (i.e., radiotherapy and/or chemotherapy).
Secondary Objective Response Rate Objective Response Rate (CR and PR by RECIST criteria version 1.1) After the end of 1st, 3rd and 5th cycle of induction therapy and before the radiotherapy. During f-up at the following time frames: 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, 60 months.
Secondary Adverse events and laboratories abnormalities. Adverse events (characterized by type, severity, timing) and laboratories abnormalities (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.03), induced by radiotherapy (both photon RT and heavy ion RT). During the treatments. F-up at the following time frames: 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, 60 months, 72 months, 84 months, 96 months.