A Phase II Clinical Trial to Evaluate the Potential of Concomitant Chemoradiotherapy With Gemcitabine in Patients With Locally Advanced Carcinoma of Cervix and Renal Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Glomerular Filtration Rate
研究概览
简要总结
From the global burden of Cervical Cancer (CC), 85% occurs in developing countries, representing 12% of cancer in women. In Mexico CC ranks second in incidence and mortality among women. The National Institute of Cancer in Mexico (lNCAN) receives annually about 500 patients with CC, 80% of which are diagnosed with locally advanced disease. Furthermore, 10 to 20% of these present kidney deterioration. The main reason for kidney disease is ureteral obstruction, other causes include age and comorbidities, such as diabetes and hypertension. The standard treatment for locally advanced disease consists in concomitant chemo-radiotherapy based on cisplatin (QT-RT), followed by brachytherapy, with an absolute benefit of 10%. However, the use of cisplatin in patients with renal disease may be questionable, considering it is a nephrotoxic treatment. Given that renal dysfunction limits the standard treatment efficiency because of the widely known nephrotoxicity of cisplatin, in most Cancer Centers of our country, patients with renal dysfunction receive only radiation therapy, even though it has proven less effective than concomitant QT-RT, limiting disease-free and overall survival of these patients. Venook et al. used gemcitabine as a radiosensitizer in patients with cancer and renal dysfunction. Our group, has observed encouraging results using gemcitabine as an alternative to cisplatin in concomitant treatment with radiotherapy, in CC patients with renal insufficiency. 89% of patients had complete response and improvement in renal function, with an enhanced creatinine clearance after treatment. Therefore, it is necessary to explore the safety of gemcitabine as an alternative treatment for CC patients with locally advanced disease and renal deterioration. We propose this clinical trial to assess the safety of treatment with gemcitabine and specifically on renal function in patients with renal deterioration. It is important to take into consideration that CC in advanced stages produces pain, transvaginal fetid discharge and general discomfort. It also causes side effects secondary to renal failure such as nausea, vomiting, fatigue, anemia, among others. These effects have a significant impact on the quality of life of these patients. Cancer treatment and its side effects, besides the implications of a nephrostomy catheter or ileostomy bag, determine the deterioration in the quality of life of the patient, during and sometimes after treatment. Thus it is of utmost importance to evaluate the factors that could help improve the quality of life of patients and explore the factors that deteriorate it. This clinical trial aims to generate scientific evidence to help make the best decisions concerning the treatment of patients with cervical cancer and renal impairment, and the impact on their quality of life.
详细描述
In Mexico, cervical cancer (CC) is the second most frequent cause of death among women, with a mortality rate of 4000 women/year. Concerning the treatment of these patients, there is evidence about the benefit of addition of chemotherapy to radiotherapy in patients with locally advanced CC, with an absolute benefit of 10% in overall survival and a significant reduction in local recurrence. Cisplatin is currently the standard treatment for CC. Evidence supports that the benefit of chemotherapy is achieved in those patients who receive at least 3 cycles of cisplatin at a dosage of 40mg/m2 weekly. The side effects of cisplatin include nephrotoxicity, neurotoxicity, nausea and vomiting, ototoxicity, electrolyte disturbance, and hemolytic anemia. For this reason, the choice of using cisplatin as a radiosensitizer requires careful consideration of the renal function of the patient, prior to the initiation of treatment. The glomerular filtration rate deteriorates with age and many patients have comorbid medical illnesses that further compromise the kidney. Gemcitabine has been tested as a single agent in CC for its radiosensitizing properties. Clinical profit has been reported along with reasonable tolerance to gemcitabine during radiotherapy. So it can be considered a good alternative treatment for the management of patients with ureteral obstruction and possible renal failure. Even though gemcitabine is well tolerated, the dosage for these patients should be considered with caution, since a specific dosage has not yet been recommended for cancer patients with renal dysfunction.
Our aim is to evaluate the safety of chemo-radiotherapy (QT-RT) concomitant with gemcitabine in patients with locally advanced cervical cancer IB2-IVA and renal deterioration. Our particular objectives are the following:
- Evaluate the renal function before, during and after treatment with QT-RT concomitant with gemcitabine.
- Assess the safety of concomitant QT-RT with gemcitabine, according to the common toxicity criteria in CTCEA v4.0.
- Determine the objective and clinical response rate after treatment with QT-RT concomitant with gemcitabine.
- Determine the incidence of percutaneous nephrostomy procedure.
- Evaluate the clinical and cabinet criteria established by the protocol for the application of percutaneous nephrostomy or double J catheter and its impact on renal function.
- Evaluate the patients' quality of life.
- Determine the frequency of complications during and after treatment with QT-RT concomitant with gemcitabine.
Our aim is based on the following hypothesis. Patients with locally advanced CC IB2-IVA and renal dysfunction, that receive concomitant QT-RT with gemcitabine, tolerate the combination with a glomerular filtration rate of >60ml/min/1.73m2, show limited toxicity (Grade l-lll) and a response rate of at least 70%.
Methods.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Gemcitabine
Gemcitabine doses: 300 mg/m2/week for 6 weeks.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Glomerular Filtration Rate
时间窗: During and every 3 months after completing concomitant QT/RT treatment, for the first two years, and every 6 months for the following 3 years.
Safety of gemcitabine regarding renal function will be assessed through glomerular filtration rate. An improvement of 10 ml/min/1.73m2 as compared to basal glomerular rate is expected by the end of treatment.
次要结局
- Toxicity of gemcitabine in patients with carcinoma of cervix and renal disease(During and every 3 months after completing concomitant QT/RT treatment, for the first two years, and every 6 months for the following 3 years.)
研究者
Lucely Cetina Pérez
MD, Master of Science
National Institute of Cancerología