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.
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
Drug | Synonyms | Arms |
---|
Cisplatin | | Multimodality treatment |
Docetaxel | | Multimodality treatment |
5-fluorouracil | | Multimodality treatment |
Etoposide | | Multimodality treatment |
Adriamycin | | Multimodality treatment |
Ifosfamide | | Multimodality treatment |
Leucovorin | | Multimodality 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
Name | Type | Description | Interventions |
---|
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.
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 |
Last Updated
October 23, 2019