Clinical trial NCT02099175: Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Operable Patients
Official title: Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors: Phase II Study of Chemotherapy, Surgery, Photon and Heavy Ion Radiotherapy Integration for More Effective and Less Toxic Treatment in Operable Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Sinonasal Tumors
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
Collaborators: name: Regione Lombardia
First posted: 2014-03-28
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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. 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.

Eligibility criteria: 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 The inclusion of the maxillary sinus carcinomas is reserved only in cases requiring exenteratio orbitae for a radical surgery.
3. AJCC stage II-III-IVa with the exception of Esthesioneuroblastoma and Intestinal Type Ethmoid Adenocarcinoma where stage III-IV only will be included.
4. Resectable 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 normal limit (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.
7. Current or concomitant enrollment in another therapeutic clinical trial.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: PFS will be assessed at 5 years.
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 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.
measure: Ocular function preservation by visual field tests.
timeFrame: 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.
measure: Hearing preservation performed by audiogram test.
timeFrame: 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.
measure: Overall safety profile of the whole treatment.
timeFrame: from the day of the Informed Consent Form signature up to 90 days after the last dose of the last therapy administered (i.e., radiotherapy and/or chemotherapy).
measure: Objective Response Rate
timeFrame: At the enrollment, at 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.
measure: Adverse events
timeFrame: During the treatments and at follow-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.
measure: Laboratories abnormalities
timeFrame: During the treatments and at follow-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.
measure: Correlation between radiological response after induction chemotherapy and pathological response in patients undergoing surgery
timeFrame: Radiological response assessed after the cycle 5 of induction chemotherapy (each cycle is 21 days); pathological response assessed after surgery (from +21days to +35 days after end of cycle 5)
measure: Quality of Life Questionnaires: EORTC QLQ-30
timeFrame: At pretreatment, after last cycle of induction chemotherapy, after surgery, at the end of treatment and during the follow-up (3,12 and 24 months)
measure: Quality of Life Questionnaires: EORTC QLQ-HN35
timeFrame: At pretreatment, after last cycle of induction chemotherapy, after surgery, at the end of treatment and during the follow-up (3,12 and 24 months)
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: Presidio Ospedaliero Spedali Civili di Brescia
state: BS
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
state: MI
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
state: PV
city: Varese
country: Italy
facility: A.O. Ospedale di Circolo e Fondazione Macchi
state: VA
city: Novara
country: Italy
facility: Azienda Ospedaliera "Maggiore della Carità"
Study officials:
affiliation: Fondazione IRCCS ISTITUTO NAZIONALE TUMORI
name: Lisa Licitra, MD
role: STUDY_DIRECTOR
affiliation: Presidio Ospedaliero Spedali Civili di Brescia
name: Piero Nicolai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Ospedale di Circolo e Fondazione Macchi
name: Paolo Calstelnuovo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Policlinico San Matteo
name: Marco Benazzo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera "Maggiore della Carità"
name: Andrea Sponghini, MD
role: PRINCIPAL_INVESTIGATOR
References: