Clinical Trials /

Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Operable Patients

NCT02099175

Description:

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.

Related Conditions:
  • Intestinal Type Sinonasal Adenocarcinoma
  • Nasal Cavity and Paranasal Sinus Small Cell Carcinoma
  • Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Olfactory Neuroblastoma
  • Sinonasal Undifferentiated Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: SINTART1
  • SECONDARY ID: 2013-000075-33
  • NCT ID: NCT02099175

Conditions

  • Sinonasal Tumors

Interventions

DrugSynonymsArms
CisplatinMultimodality treatment
DocetaxelMultimodality treatment
5-fluorouracilMultimodality treatment
EtoposideMultimodality treatment
AdriamycinMultimodality treatment
IfosfamideMultimodality treatment
LeucovorinMultimodality treatment

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Multimodality treatmentExperimentalSquamocellular 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
  • Cisplatin
  • Docetaxel
  • 5-fluorouracil
  • Etoposide
  • Adriamycin
  • Ifosfamide
  • Leucovorin

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:PFS will be assessed at 5 years.
Safety Issue:
Description: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 Outcome Measures

Measure:Overall survival (OS)
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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description:Ocular function preservation by visual field tests.
Measure: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.
Safety Issue:
Description:Hearing preservation performed by audiogram test
Measure:Overall safety profile of the whole treatment.
Time Frame: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).
Safety Issue:
Description: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.
Measure:Objective Response Rate
Time Frame: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.
Safety Issue:
Description:Objective Response Rate (CR and PR by RECIST criteria version 1.1)
Measure:Adverse events
Time Frame: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.
Safety Issue:
Description:Adverse events (characterized by type, severity, timing) (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).
Measure:Laboratories abnormalities
Time Frame: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.
Safety Issue:
Description: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).
Measure:Correlation between radiological response after induction chemotherapy and pathological response in patients undergoing surgery
Time Frame: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)
Safety Issue:
Description:Radiological response as per RECIST criteria (version 1.1) after last cycle of induction CT; pathological response defined as obtaining or not a pathologic complete response (i.e., absence of any residual viable tumor cell).
Measure:Quality of Life Questionnaires: EORTC QLQ-30
Time Frame: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)
Safety Issue:
Description:Quality of Life (QoL) according to EORTC QLQ-30.
Measure:Quality of Life Questionnaires: EORTC QLQ-HN35
Time Frame: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)
Safety Issue:
Description:Quality of Life (QoL) according to EORTC QLQ-HN35

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Last Updated