Phase III Trial of Laryngeal Preservation Comparing Induction Chemotherapy With Cisplatin, 5-fluorouracil and Docetaxel (TPF) Followed by Radiotherapy and Concomitant Administration of Radiotherapy With Cisplatin
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 256
- 试验地点
- 1
- 主要终点
- free survival
研究概览
简要总结
This study compare the survival without laryngeal dysfunction 2 years after the end of treatment, obtained by chemotherapy followed by radiotherapy or chemotherapy with cisplatin administrated during radiotherapy.
详细描述
In patients with tumors classified as T3 or T4 larynx and hypopharynx, the usually recommended treatment was total laryngectomy.This intervention allows to obtain locoregional disease control in 75% of cases, without laryngectomy
TPF arm followed by radiotherapy was validated in a Phase III (GORTEC 2000-01), it will be the standard treatment.
The RTOG study concluded that chemotherapy administrated during radiotherapy became a standard of laryngeal preservation.
Taking together all these considerations, it is necessary to perform a direct comparison in a randomized trial to further test this hypothesis. Chemotherapy followed by radiotherapy will be the standard arm. It hopes to increase the survival rate from 52% to 65% in the experimental arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Squamous cell carcinoma of the larynx or hypopharynx, histologically proven, locally advanced:
- •T2 not accessible to a supra-cricoid partial laryngectomy or not,
- •T3 without massive infiltration by endolarynx transglottic injury,
- •N0 to N2c
- •No distant metastasis
- •No associated cancer or earlier
- •Patients Previously Untreated
- •Age> 18 years and <75 years
- •PS 0 or 1 according to WHO
- •Tumor volume assessable by RECIST.
- •Absence of distant metastasis, confirmed by chest TDM, abdominal ultrasound (or TDM) in case of abnormal liver function and bone scan if local symptoms.
- •Absence of any participation in a clinical trial within 30 days prior to inclusion.
- •Absence of any concomitant cancer treatment.
- •Absence of any chronic treatment ( ≥3 months) with a daily corticosteroid dose is ≥20 mg / day of methylprednisolone or equivalent.
- •Hematological function: neutrophils ≥1.5 x 109 / L, platelets ≥100 x 109 / l, hemoglobin ≥10 g / dl (or 6.2 mmol / l).
- •Hepatic function: normal total bilirubin; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN (LNS) of each center; alkaline phosphatase ≤ 5 x LNS.
- •Renal function: serum creatinine ≤ 120 mol / l (1.4 mg / dl); if creatinine > 120 mol / l, creatinine clearance should be ≥ 60 ml / min.
- •calculated creatinine clearance (Crockcroft formula) or measured ≥ 60 ml / min
- •Estimated life expectancy ≥ 3 months
- •Weight loss less than 10% over the last 3 months
- •Patient has given its written consent before any specific procedure of the Protocol.
- •Women and men of childbearing age should have accepted a medically effective contraception during the treatment period and at least 6 months after discontinuation of study treatments (Docetaxel, 5-Fluorouracil and Cisplatin. If pregnancy is declared by a patient or partner of a patient, it must be followed to know the evolution of pregnancy.
排除标准
- •transglottic T3 with massive infiltration of hemilarynx or T4 with massive cartilaginous tumor lysis or reverse cricoarythénoïdenne region or posterior hypopharyngeal wall
- •tumor requiring the completion of an immediately tracheotomy.
- •Tumour available immediately to partial surgery.
- •tumor requiring circular hypopharyngectomie
- •N3 nodal injury
- •Vaccination against yellow fever recent or anticipated
- •Deficit known dihydropyrimidine dehydrogenase (DPD)
- •Other malignancies within 5 years prior to randomization, with the exception of adequately treated basal skin cancer and carcinoma in situ of the cervix.
- •Patients with AST or ALT> 1.5xULN associated with alkaline phosphatase > 2.5x LNS will not be eligible for testing.
- •symptomatic neuropathy grade ≥2 with NCI-CTC.
- •Clinical alteration of hearing function.
- •Other concomitant serious medical conditions (partial list):
- •Unstable cardiac disease despite treatment.
- •Myocardial infarction within 6 months prior to trial entry.
- •Neurological or psychiatric history such as dementia, seizures;
- •Severe uncontrolled infection.
- •Significant gastrointestinal abnormalities, including those that require parenteral nutrition, active peptic ulcer disease and a history of surgical procedures affecting absorption
- •Obstructive pulmonary disease requiring hospitalization in the year before inclusion.
- •Unstable diabetes or other cons-indications to corticosteroids.
- •Significant ophthalmologic abnormality.
- •Moderate or severe eczema.
- •Allergy to iodine.
- •Hypersensitivity to Docetaxel, Cisplatin or at one of their excipients.
- •Concomitant use of phenytoin, carbamazepine, barbiturates and rifampicin.
- •Presence, selection, psychological factors, family, social or geographical may alter patient compliance with the study protocol and follow-up, a criterion of non-inclusion. These factors should be discussed with the patient before inclusion in the trial.
- •Pregnant or nursing women.
- •Patient (male or female) of childbearing age not taking adequate contraceptive measures.
- •Patient deprived of their liberty, without guardianship or curatorship.
研究组 & 干预措施
TPF followed by radiotherapy
Induction chemotherapy by Docetaxel 75 mg/m² day 1,cisplatin 75 mg/m² day 1 and 5 fluorouracil 750mg/m²(day 1 to day 5) 3 cycles day1, day 22, day 43 followed (for responders or stable disease patients) by radiotherapy
Radiotherapy ;70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
干预措施: Docetaxel (Drug)
TPF followed by radiotherapy
Induction chemotherapy by Docetaxel 75 mg/m² day 1,cisplatin 75 mg/m² day 1 and 5 fluorouracil 750mg/m²(day 1 to day 5) 3 cycles day1, day 22, day 43 followed (for responders or stable disease patients) by radiotherapy
Radiotherapy ;70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
干预措施: Cisplatin (Drug)
TPF followed by radiotherapy
Induction chemotherapy by Docetaxel 75 mg/m² day 1,cisplatin 75 mg/m² day 1 and 5 fluorouracil 750mg/m²(day 1 to day 5) 3 cycles day1, day 22, day 43 followed (for responders or stable disease patients) by radiotherapy
Radiotherapy ;70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
干预措施: Fluorouracil (Drug)
TPF followed by radiotherapy
Induction chemotherapy by Docetaxel 75 mg/m² day 1,cisplatin 75 mg/m² day 1 and 5 fluorouracil 750mg/m²(day 1 to day 5) 3 cycles day1, day 22, day 43 followed (for responders or stable disease patients) by radiotherapy
Radiotherapy ;70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
干预措施: radiotherapy (Radiation)
Cisplatin and radiotherapy
Drug and radiation • Cisplatin: 100 mg / m² administered IV at J1, J22 and J43 of radiotherapy
. Radiotherapy 70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
干预措施: Cisplatin (Drug)
Cisplatin and radiotherapy
Drug and radiation • Cisplatin: 100 mg / m² administered IV at J1, J22 and J43 of radiotherapy
. Radiotherapy 70 gray fractionization: 2Gy/day, 5days/week, for 7 weeks.
干预措施: radiotherapy (Radiation)
结局指标
主要结局
free survival
时间窗: 24 months after treatment initiation
Minimum time between randomization and the occurrence of events such as: death, total laryngectomy, tracheotomy.
次要结局
- Overall survival(60 months)
- Progression free survival(60 months)
- Larynx Preservation(24 months after treatment initiation)
- Feasibility of salvage surgery(60 months after randomization)