Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Operable Patients

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Status and phase

Unknown

Phase 2

Conditions

Sinonasal Tumors

Treatments

Drug: Leucovorin

Radiation: Radiotherapy - Patients needing Elective Nodal Volume (ENI)

Drug: Docetaxel

Drug: Adriamycin

Radiation: Radiotherapy - Patients needing curative neck irradiation

Drug: Etoposide

Drug: 5-fluorouracil

Drug: Cisplatin

Radiation: Radiotherapy - Patients not needing ENI

Drug: Ifosfamide

Study type

Interventional

Funder types

Other

Identifiers

NCT02099175

2013-000075-33 (EudraCT Number)

SINTART1

Details and patient eligibility

About

Sinonasal tumors are rare diseases, so no standard treatment for such aggressive tumors has been reported, given rarity, absence of prospective study and heterogeneity of histologies and stages of diseases. This study proposes innovative integration of multiple modality of treatment depending by histology, molecular profile and response to induction CT. Moreover, such strategies allows the use of latest technology with greater biological effectiveness and reduction of toxicities.

Full 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. In this scenario, multimodality treatment seems the best approach, even if there is lack of prospective data.

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.

In addition, heavy ion therapy may produce less toxic side effects in a particularly critical area exposed to late RT toxicities and potentially can help in organ preservation strategies when exenteratio orbitae is requested.

Enrollment

41 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed and dated IEC-approved Informed Consent
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 The inclusion of the maxillary sinus carcinomas is reserved only in cases requiring exenteratio orbitae for a radical surgery.
AJCC stage II-III-IVa with the exception of Esthesioneuroblastoma and Intestinal Type Ethmoid Adenocarcinoma where stage III-IV only will be included.
Resectable disease.
ECOG performance status 0-2.
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 normal limit (ULN).
Polychemotherapy treatment clinical feasibility as per Investigator's Judgment.
Male or female patients ≥ 18 years of age.
Negative pregnancy test (if female in reproductive years).
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

Previous radiotherapy or chemotherapy for head and neck district tumors (surgical treatment relapses are admitted).
Metastatic disease.
Cardiac, pulmonary, infective, neurological disease or any other medical condition that could interfere with treatment.
Unable and unwilling to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol.
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).
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.
Current or concomitant enrollment in another therapeutic clinical trial.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

41 participants in 1 patient group

Multimodality treatment

Experimental group

Description:

Squamocellular Carcinoma, Sinonasal Undifferentiated Carcinoma: * Docetaxel at 75 mg/m2 as IV infusion on Day 1 q3w * Cisplatin at 80 mg/m2 as IV infusion on Day 1 q3w * 5-fluorouracil at 800 mg/m2/day as IV infusion from Day 1 to Day 4 q3w Small cell carcinoma neuroendocrine type, Pure neuroendocrine carcinoma and grade III-IV Esthesioneuroblastoma: First Cycle and every other cycle: * Cisplatin at 33 mg/m2/day as IV infusion from Day 1 to Day 3 q3w * Etoposide at 150 mg/m2/day as IV infusion from Day 1 to Day 3 q3w Second Cycle and every other cycle: * Adriamycin at 20 mg/m2/day as IV infusion from Day 1 to Day 3 q3w * Ifosfamide at 3000 mg/m2/day as IV infusion from Day 1 to Day 3 q3w Intestinal Type Adenocarcinoma with functional p53: * Leucovorin\* at 250 mg/m2/day as IV infusion from Day 1 to Day 5 q3w * Cisplatin at 100 mg/m2 as IV infusion on Day 2 q3w * 5-fluorouracil at 800 mg/m2/day as IV infusion from Day 2 to Day 5 q3w Followed by Radiotherapy

Treatment: