Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Inoperable Patients

Phase 2UnknownNCT02099188

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano27 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Unresectable Sinonasal Tumors

Interventions

CisplatinDRUG

80 mg/m2 or 33 mg/m2/day or 100 mg/m2 - Concentrate for solution for infusion

DocetaxelDRUG

75 mg/m2 - Concentrate for solution for infusion

5-fluorouracilDRUG

800 mg/m2/day - Concentrate for solution for infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (5)

Presidio Ospedaliero Spedali Civili di Brescia

Brescia, BS, Italy

Fondazione IRCCS Istituto Nazionale Tumori

Milan, MI, Italy

IRCCS Policlinico San Matteo

Pavia, PV, Italy

A.O. Ospedale di Circolo e Fondazione Macchi

Varese, VA, Italy

Outcomes

Primary Outcomes

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.

Time frame: PFS will be assessed at 5 years.

Secondary Outcomes

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.

Time frame: 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.

Ocular function preservation by visual field tests.

Time frame: 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.

Hearing preservation performed by audiogram test.

Time frame: 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.

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.

Time frame: 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).

Data from ClinicalTrials.gov

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