- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02099188
Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors in Inoperable Patients
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
- 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
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Novara, Italy, 28100
- Azienda Ospedaliera "Maggiore della Carità"
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BS
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Brescia, BS, Italy, 25125
- Presidio Ospedaliero Spedali Civili di Brescia
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MI
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Milano, MI, Italy, 20133
- Fondazione IRCCS Istituto Nazionale Tumori
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PV
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Pavia, PV, Italy, 27100
- IRCCS Policlinico San Matteo
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VA
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Varese, VA, Italy, 21100
- A.O. Ospedale di Circolo e Fondazione Macchi
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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;
- Esthesioneuroblastoma with differentiation grade III-IV by Hyams.
- AJCC stage T4b.
- Unresectable 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 limit of normal (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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Multimodality treatment
Squamocellular Carcinoma, Sinonasal Undifferentiated Carcinoma:
Small cell carcinoma neuroendocrine type, Pure neuroendocrine carcinoma and grade III-IV Esthesioneuroblastoma.
Intestinal Type Adenocarcinoma with functional p53.
Followed by radiotherapy |
80 mg/m2 or 33 mg/m2/day or 100 mg/m2 - Concentrate for solution for infusion
Other Names:
75 mg/m2 - Concentrate for solution for infusion
Other Names:
800 mg/m2/day - Concentrate for solution for infusion
Other Names:
150 mg/m2/day - Concentrate for solution for infusion
Other Names:
20 mg/m2/day - Powder for solution for infusion
Other Names:
3000 mg/m2/day - Powder for solution for infusion
Other Names:
250 mg/m2/day - Powder for solution for infusion
Other Names:
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.
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: PFS will be assessed at 5 years.
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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.
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PFS will be assessed at 5 years.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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.
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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.
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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.
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Ocular function preservation by visual field tests.
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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.
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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.
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Hearing preservation performed by audiogram test.
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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.
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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).
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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.
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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).
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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.
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Objective Response Rate (CR and PR by RECIST criteria version 1.1)
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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.
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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.
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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).
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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.
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Collaborators and Investigators
Collaborators
Investigators
- Study Director: Lisa Licitra, MD, Fondazione IRCCS Istituto Nazionale Tumori
- Principal Investigator: Piero Nicolai, MD, Presidi Ospedalieri Spedali Civili di Brescia
- Principal Investigator: Paolo Castelnuovo, MD, A.O. Ospedale di Circolo e Fondazione Macchi
- Principal Investigator: Marco Benazzo, MD, IRCCS Policlinico San Matteo
- Principal Investigator: Letizia Deantonio, MD, Azienda Ospedaliera "Maggiore della Carità"
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Micronutrients
- Antibiotics, Antineoplastic
- Vitamins
- Antidotes
- Vitamin B Complex
- Docetaxel
- Etoposide
- Fluorouracil
- Ifosfamide
- Leucovorin
- Doxorubicin
- Liposomal doxorubicin
Other Study ID Numbers
- SINTART2
- 2013-000580-93 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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