Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Inoperable Patients

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Status and phase: Unknown; Phase 2

Conditions: Unresectable Sinonasal Tumors

Treatments: Radiation: Radiotherapy - Patients needing curative neck irradiation; Drug: 5-fluorouracil; Drug: Cisplatin; Radiation: Radiotherapy - Patients not needing ENI; Drug: Docetaxel; Drug: Leucovorin; Drug: Adriamycin; Radiation: Radiotherapy - Patients needing Elective Nodal Volume (ENI); Drug: Ifosfamide; Drug: Etoposide

Study type: Interventional

Funder types: Other

Identifiers

NCT02099188

SINTART2

2013-000580-93 (EudraCT Number)

Details and patient eligibility

About

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.

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. 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.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 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. * 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:

Drug: Etoposide

Radiation: Radiotherapy - Patients needing curative neck irradiation

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

Drug: Ifosfamide

Drug: Adriamycin

Drug: Leucovorin

Drug: Docetaxel

Radiation: Radiotherapy - Patients not needing ENI

Drug: 5-fluorouracil

Drug: Cisplatin