Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Inoperable Patients

NCT ID: NCT02099188

Last Updated: 2023-03-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2024-01-31

Brief Summary

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.

Conditions

Unresectable Sinonasal Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Multimodality treatment

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

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

75 mg/m2 - Concentrate for solution for infusion

5-fluorouracil

Intervention Type: DRUG

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

Etoposide

Intervention Type: DRUG

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

Adriamycin

Intervention Type: DRUG

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

Ifosfamide

Intervention Type: DRUG

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

Leucovorin

Intervention Type: DRUG

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

Radiotherapy - Patients needing Elective Nodal Volume (ENI)

Intervention Type: 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 with ENI:

HR-PTV: carbon ions 18 - 21 Gy (relative biological effectiveness, 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 setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed.

Radiotherapy - Patients not needing ENI

Intervention Type: 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 setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed.

Radiotherapy - Patients needing curative neck irradiation

Intervention Type: 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.

Interventions

Cisplatin

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

Intervention Type: DRUG

Docetaxel

75 mg/m2 - Concentrate for solution for infusion

Intervention Type: DRUG

5-fluorouracil

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

Intervention Type: DRUG

Etoposide

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

Intervention Type: DRUG

Adriamycin

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

Intervention Type: DRUG

Ifosfamide

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

Intervention Type: DRUG

Leucovorin

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

Intervention Type: DRUG

Radiotherapy - Patients needing Elective Nodal Volume (ENI)

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 with ENI:

HR-PTV: carbon ions 18 - 21 Gy (relative biological effectiveness, 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 setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed.

Intervention Type: RADIATION

Radiotherapy - Patients not needing ENI

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 setting will be prescribed. IR-PTV: 59.4-60 Gy with 1.8 Gy-2 Gy per fraction will be prescribed.

Intervention Type: RADIATION

Radiotherapy - Patients needing curative neck irradiation

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.

Intervention Type: RADIATION

Other Intervention Names

CDDP; Taxotere; Adrucil; Vepesid; Doxorubicin; Ifex; Folinic acid

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regione Lombardia

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa Licitra, MD

Role: STUDY_DIRECTOR

Fondazione IRCCS ISTITUTO NAZIONALE TUMORI

Piero Nicolai, MD

Role: PRINCIPAL_INVESTIGATOR

Presidi Ospedalieri Spedali Civili di Brescia

Paolo Castelnuovo, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Ospedale di Circolo e Fondazione Macchi

Marco Benazzo, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Policlinico San Matteo

Letizia Deantonio, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera "Maggiore della Carità"

Locations

Presidio Ospedaliero Spedali Civili di Brescia

Brescia, BS, Italy

Fondazione IRCCS Istituto Nazionale Tumori

Milan, MI, Italy

IRCCS Policlinico San Matteo

Pavia, PV, Italy

A.O. Ospedale di Circolo e Fondazione Macchi

Varese, VA, Italy

Azienda Ospedaliera "Maggiore della Carità"

Novara, , Italy

Countries

Italy

Other Identifiers

2013-000580-93

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SINTART2

Identifier Type: -

Identifier Source: org_study_id