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
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Cisplatin (Drug)
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
干预措施: Docetaxel (Drug)
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
干预措施: 5-fluorouracil (Drug)
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
干预措施: Etoposide (Drug)
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
干预措施: Adriamycin (Drug)
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
干预措施: Ifosfamide (Drug)
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
干预措施: Leucovorin (Drug)
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
干预措施: Radiotherapy - Patients needing Elective Nodal Volume (ENI) (Radiation)
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
干预措施: Radiotherapy - Patients not needing ENI (Radiation)
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
干预措施: Radiotherapy - Patients needing curative neck irradiation (Radiation)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: PFS will be assessed at 5 years.
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.
次要结局
- 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.)
- Adverse events and laboratories abnormalities.(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.)
- Overall safety profile of the whole treatment.(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).)
- 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.)
- 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.)
- Objective Response Rate(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.)