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Sinonasal TumorsPhase 2NCT02099175

Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Operable Patients

A Phase 2 study testing Cisplatin, Docetaxel and 5-fluorouracil in people with Sinonasal Tumors, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 5 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sinonasal Tumors
What is being tested?
Cisplatin, Docetaxel and 5-fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
5 sitesItaly
Study dates
Nov 2013to Jan 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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);
Show all 16Show fewer
  • 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.
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Italy5 sites

  • Presidio Ospedaliero Spedali Civili di Brescia

    Brescia, BS, 25125

  • Fondazione IRCCS Istituto Nazionale Tumori

    Milan, MI, 20133

  • Azienda Ospedaliera "Maggiore della Carità"

    Novara, 28100

  • IRCCS Policlinico San Matteo

    Pavia, PV, 27100

  • A.O. Ospedale di Circolo e Fondazione Macchi

    Varese, VA, 21100

Other trials in Italy

About this study

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

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.

Read the 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.

Being tested
Cisplatin, Docetaxel, 5-fluorouracil, Etoposide, Adriamycin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CisplatinDrug

    Also called CDDP

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

  • DocetaxelDrug

    Also called Taxotere

    75 mg/m2 - Concentrate for solution for infusion

  • 5-fluorouracilDrug

    Also called Adrucil

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

  • EtoposideDrug

    Also called Vepesid

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

  • AdriamycinDrug

    Also called Doxorubicin

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

  • IfosfamideDrug

    Also called Ifex

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

  • LeucovorinDrug

    Also called Folinic acid

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

  • 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

  • Radiotherapy - Patients not needing ENIRadiation

    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

  • Radiotherapy - Patients needing curative neck irradiationRadiation

    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.

Study groups in NCT02099175
Study groupRoleWhat they receive
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
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: PFS will be assessed at 5 years.

Secondary outcomes (10)

  1. Overall survival (OS)

    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.

    Measured: 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.

  2. Ocular function preservation by visual field tests.

    Ocular function preservation by visual field tests.

    Measured: 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.

  3. Hearing preservation performed by audiogram test.

    Hearing preservation performed by audiogram test

    Measured: 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.

  4. Overall safety profile of the whole treatment.

    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.

    Measured: 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).

  5. Objective Response Rate

    Objective Response Rate (CR and PR by RECIST criteria version 1.1)

    Measured: 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.

  6. Adverse events

    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).

    Measured: 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.

  7. Laboratories abnormalities

    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).

    Measured: 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.

  8. Correlation between radiological response after induction chemotherapy and pathological response in patients undergoing surgery

    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).

    Measured: 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)

  9. Quality of Life Questionnaires: EORTC QLQ-30

    Quality of Life (QoL) according to EORTC QLQ-30.

    Measured: 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)

  10. Quality of Life Questionnaires: EORTC QLQ-HN35

    Quality of Life (QoL) according to EORTC QLQ-HN35

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2014 (estimated)
  2. Study startNov 2013
  3. Primary completionJan 2020
  4. Study completionJan 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02099175
Sponsor's protocol ID
SINTART1
Other IDs
2013-000075-33
Status last verified
Apr 2022
First submitted
14 Mar 2014
Last updated
13 Mar 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cisplatin, Docetaxel and 5-fluorouracil in people with Sinonasal Tumors, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 5 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: PFS will be assessed at 5 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02099175.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2023.

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