Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Operable Patients

NCT02099175 | Unknown Phase 2 DMC

• 2 other identifiers: SINTART12013-000075-33
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 5

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.

Conditions

Sinonasal Tumors

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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

  PFS will be assessed at 5 years.

Secondary Outcomes (10)

• Overall survival (OS)

  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.

• Ocular function preservation by visual field tests.

  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.

• Hearing preservation performed by audiogram test.

  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.

• Overall safety profile of the whole treatment.

  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).

• Objective Response Rate

  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.

Study Arms (1)

Multimodality treatment

EXPERIMENTAL

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

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

Interventions

Cisplatin DRUG

80 mg/m2 or 33 mg/m2 or 100 mg/m2 - Concentrate for solution for infusion.

Also known as: CDDP

Multimodality treatment

Docetaxel DRUG

75 mg/m2 - Concentrate for solution for infusion

Also known as: Taxotere

Multimodality treatment

5-fluorouracil DRUG

800 mg/m2/day - Concentrate for solution for infusion

Also known as: Adrucil

Multimodality treatment

Etoposide DRUG

150 mg/m2/day - Concentrate for solution for infusion

Also known as: Vepesid

Multimodality treatment

Adriamycin DRUG

20 mg/m2/day - Powder for solution for infusion

Also known as: Doxorubicin

Multimodality treatment

Ifosfamide DRUG

3000 mg/m2/day - Powder for solution for infusion

Also known as: Ifex

Multimodality treatment

Leucovorin DRUG

250 mg/m2/day - Powder for solution for infusion

Also known as: Folinic acid

Multimodality treatment

Radiotherapy - Patients needing Elective Nodal Volume (ENI) RADIATION

1. Particle boost with ENI: HR-PTV: carbon ions 18 - 21 Gy (RBE) in fractions of 3 Gy (RBE) without concomitant chemotherapy IR-PTV: this volume is optional, if used it will receive the first 3 fractions i.e. 9 Gy (RBE) of the boost. 2. Photons boost with ENI: HR-PTV: at least 70 Gy with 2-2.12 Gy per fraction and 66 Gy at 2Gy per fraction in radical and postoperative setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed

Multimodality treatment

Radiotherapy - Patients not needing ENI RADIATION

1. Treatment with particles IR-PTV: this volume can be larger or equal to HR-PTV according to individual situations. 50.4-54 Gy with 1.8-2 Gy per fraction will be prescribed to IR-PTV with protontherapy with concomitant chemotherapy. HR-PTV: carbon ions 18 - 21 Gy (RBE) in fractions of 3 Gy (RBE) without concomitant chemotherapy. The first 3 fractions may be given to the bigger IR-PTV. 2. Treatment with photons. HR-PTV: at least 70 Gy with 2-2.12 Gy per fraction and 66 Gy at 2Gy per fraction in radical and postoperative setting will be prescribed. IR-PTV: 54-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed

Multimodality treatment

Radiotherapy - Patients needing curative neck irradiation RADIATION

LR-PTV: 50.4-54 Gy with 1.8-2 Gy per fraction will be prescribed. This volume will always be treated with photons IMRT. 1. Particle boost: HR-PTV: carbon ions 18 - 21 Gy (RBE) in fractions of 3 Gy (RBE) without concomitant chemotherapy IR-PTV: this volume is optional, if used it will receive the first 3 fractions i.e. 9 Gy (RBE) of the boost. 2. Photons boost. HR-PTV: at least 70 Gy with 2-2.12 Gy per fraction and 66 Gy at 2Gy per fraction in radical and postoperative setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed. Concomitant chemotherapy will be administered only in case of radiotherapy with photon beams exclusively.

Multimodality treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• Regione Lombardia: collaborator

Study Sites (5)

Presidio Ospedaliero Spedali Civili di Brescia

Brescia, BS, 25125, Italy

Location

Fondazione IRCCS Istituto Nazionale Tumori

Milan, MI, 20133, Italy

Location

IRCCS Policlinico San Matteo

Pavia, PV, 27100, Italy

Location

A.O. Ospedale di Circolo e Fondazione Macchi

Varese, VA, 21100, Italy

Location

Azienda Ospedaliera "Maggiore della Carità"

Novara, 28100, Italy

Location

MeSH Terms

Interventions

Cisplatin; Docetaxel; Fluorouracil; Etoposide; Doxorubicin; Ifosfamide; Leucovorin

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Lisa Licitra, MD

  Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

  STUDY DIRECTOR

• Piero Nicolai, MD

  Presidio Ospedaliero Spedali Civili di Brescia

  PRINCIPAL INVESTIGATOR

• Paolo Calstelnuovo, MD

  A.O. Ospedale di Circolo e Fondazione Macchi

  PRINCIPAL INVESTIGATOR

• Marco Benazzo, MD

  IRCCS Policlinico San Matteo

  PRINCIPAL INVESTIGATOR

• Andrea Sponghini, MD

  Azienda Ospedaliera "Maggiore della Carità"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2014
• First Posted: March 28, 2014
• Study Start: November 1, 2013
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2024
• Last Updated: March 13, 2023

Record last verified: 2022-04

Locations

IT (5)