Clinical Trials /

Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Inoperable Patients

NCT02099188

Description:

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.

Related Conditions:
  • Intestinal Type Sinonasal Adenocarcinoma
  • Nasal Cavity and Paranasal Sinus Neuroendocrine Carcinoma
  • Nasal Cavity and Paranasal Sinus Small Cell Neuroendocrine 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 Inoperable Patients
  • Official Title: Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors: Phase II Study of Chemotherapy, Photon and Heavy Ion Radiotherapy Integration for More Effective and Less Toxic Treatment in Inoperable Patients

Clinical Trial IDs

  • ORG STUDY ID: SINTART2
  • SECONDARY ID: 2013-000580-93
  • NCT ID: NCT02099188

Conditions

  • Unresectable 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, 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.
    

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. 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.

          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.
      
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 through 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: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.
Safety Issue:
Description:Objective Response Rate (CR and PR by RECIST criteria version 1.1)
Measure:Adverse events and laboratories abnormalities.
Time Frame: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.
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

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