Unresectable Sinonasal Tumors
Conditions
Brief 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.
Detailed 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.
Interventions
DRUGCisplatin
80 mg/m2 or 33 mg/m2/day or 100 mg/m2 - Concentrate for solution for infusion
DRUGDocetaxel
75 mg/m2 - Concentrate for solution for infusion
DRUG5-fluorouracil
800 mg/m2/day - Concentrate for solution for infusion
DRUGEtoposide
150 mg/m2/day - Concentrate for solution for infusion
DRUGAdriamycin
20 mg/m2/day - Powder for solution for infusion
DRUGIfosfamide
3000 mg/m2/day - Powder for solution for infusion
DRUGLeucovorin
250 mg/m2/day - Powder for solution for infusion
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. 1. 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. 2. 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.
1. 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. 2. 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.
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. 1. 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. 2. 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.
Sponsors
Regione Lombardia
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | PFS will be assessed at 5 years. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Ocular function preservation by visual field tests. |
| 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. | Hearing preservation performed by audiogram test. |
| Overall survival (OS) | 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. | 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. |
| Objective Response Rate | 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. | Objective Response Rate (CR and PR by RECIST criteria version 1.1) |
| Adverse events and laboratories abnormalities. | 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. | 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). |
| Overall safety profile of the whole treatment. | 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). | 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. |
Countries
Italy
Outcome results
None listed