Induction Versus Adjuvant Gemcitabine/Cisplatin in Locally Advanced Non-metastatic Nasopharyngeal Carcinoma: A Randomized Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Loco regional control rates (LCR)
研究概览
简要总结
The standard of care for locally advanced nasopharyngeal carcinoma is radical chemoradiation(CRT).Recent advances in radiation techniques and supportive measures resulted in improvemnent of locoregional control and quality of life.However distant failure is still the main challenging reason of poor survival
Addition of systemic therapy to concurrent CRT is widely used and accepted as an option to reduce these failures ,however selection of chemotherapy regimen and timing in relation to CRT is controversial.
Doublet and triplet chemotherapy regimens using cisplatin and 5FU are throughly investigated in this setting.Inspite of significant improvement in disease free survival and overall survival they were poorly tolerated.Hence,minority of patients in the daily practice could tolerate those studied regimens as propsed.
Recently, in multicenter randomized trial, Zhang and his group investigated gemcitabine and cisplatin as induction chemotherapy (ICT) added to CRT.It showed improvement in recurrence free survival and overall survival.More importantly 96.7% of the experimental arm completed the treatment protocol.
This was further confirmed by an updated network of meta analysis by Bongiovanni et al.Again the question of "when" is still valid.Our proposal is to compare tolerable regimen in induction versus adjuvant settings.
详细描述
Background
Nasopharyngeal carcinoma (NPC) is one of the cancers which shows significant geographic prevalence variation. Worldwide, there were 130,000 new cases in 2018.As a non-endemic region, only 35 new cases were diagnosed in Kuwait in the same year. Nevertheless, it accounts for 1.3% of cancer related mortality in Kuwait.
Radical radiotherapy (RT) is the mainstay treatment of NPC for decades. A high cure rate can be achieved for patients with early-stage. The breakthrough in the management of NPC came with the intergroup study 009 which showed significant improved progression free survival with adding chemotherapy (CTH) to the radiation.
As compared to RT alone, concurrent chemoradiation (CRT), showed significant improvement in 10-year overall survival and progression free survival in meta-analysis of nasopharyngeal carcinoma (MAC-NPC) collaborative group. Addition of systemic therapy to concurrent CRT was the proposed solution to treatment failures; whether in the induction (ICT) or adjuvant (ACT) settings. However, ICT or ACT in NPC remains controversial; largely due to inconsistent results of several prospective randomized trials.
The above-mentioned MAC-NPC group reviewed six clinical trials in which CRT followed by ACT was compared with RT alone (administrated without concurrent or adjuvant chemotherapy). Overall survival (OS) was significantly improved compared with RT alone (10-year overall survival 57% versus 43.1%, HR 0.65, 95% CI 0.56-0.76), as well as 10-year progression-free survival; PFS (53.2% versus 38.5%).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly histologically confirmed Nasopharyngeal carcinoma (according to World Health Organization (WHO)
- •The patient has stage III except T3N0 or IVA disease (according to 8th American Joint Committee on Cancer staging system)
- •WHO performance status 0-1 .
- •The patient must have achieved lawful age to provide informed consent according to local or national law .
- •Laboratory values performed within 14 days prior to concurrent chemotherapy should be as follows: i) Absolute neutrophil count (ANC) ≥ 1500/mm ii) Platelet count ≥ 100.000/mm iii) Hemoglobin ≥ 8g/dl iv) Urea and serum creatinine ≤ 1.5 mg/dl. (for cisplatin) v) Creatinine clearance ≥ 60 ml/min. (for cisplatin) vi) SGOT and SGPT ≤ 2 × upper limit of laboratory normal
- •Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
排除标准
- •Age ≥70 or <18
- •The patient has evidence of distant metastatic disease.
- •The patient has received prior systemic chemotherapy within the last three years.
- •The patient has undergone previous surgery for the tumor, other than biopsy.
- •The patient has received prior radiation therapy to the head or neck
- •The patient is pregnant or breast feeding.
- •The patient has a medical (e.g. renal impairment) or psychological condition that would not permit the patient to complete the trial or sign informed consent.
- •Has known history of Human Immunodeficiency Virus (HIV)
- •Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy,
- •Has a history of severe hypersensitivity reaction to Cisplatin, Gemcitabine or radiotherapy or their analogs
- •Unstable cardiac disease requiring treatment.
研究组 & 干预措施
Adjuvant Arm
Patients will receive radical CRT followed by three cycles of AC Gemcitabin/Cisplatin
干预措施: Gemcitabin/cisplatin (Drug)
Induction Arm
patients will receive three cycles of IC Gemcitabin/Cisplatin followed by radical CRT
干预措施: Gemcitabin/cisplatin (Drug)
结局指标
主要结局
Loco regional control rates (LCR)
时间窗: 3-5 years
Defined as the time from the date of randomization to 1st failure in nasopharynx or neck lymph nodes
Progression free survival (PFS)
时间窗: 3-5 Years
Defined as the time from the date of randomization to 1st failure locally or systemically
Acute and late toxicity assessment
时间窗: 3-5 years
Incidence of acute toxicity is calculated for each adverse event respectively, and severity evaluated on based of common terminology criteria for adverse event (CTCAE)
Late radiation toxicity
时间窗: 5-7 years
assessed using the radiation therapy oncology group and Europe organization for research and treatment of cancer late radiation morbidity scoring scheme
次要结局
- Distance Metastasis free survival (DMFS)(5 years)
- Overall Survival (OS)(5 years)
研究者
Shereen Issa
Dr Shereen Issa, MD
Kuwait Cancer Control Center