Radiotherapy Plus Concomitant Temozolomide for Refractory Pituitary Adenomas，A Randomized，Double-blind, Placebo-controlled Phase II Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 150
- 主要终点
- Tumor size
研究概览
简要总结
The purpose of this study was to determine whether radiotherapy combined with Temozolomide is more effective than radiotherapy alone in the treatment of patients with refractory pituitary adenomas. The Basic treatment was Radiotherapy over a period of six weeks, for a total dose of 54 Gy. The150 participants were randomized to use either radiotherapy plus Temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), or radiotherapy plus placebo for 6 weeks. After a 4-week break, followed by six cycles of placebo or adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was Objective Response rate, the second end point was PFS. Greater response was anticipated in patients treated with Temozolomide+ radiotherapy than radiotherapy alone.
详细描述
The purpose of this study was to determine whether radiotherapy combined with Temozolomide is more effective than radiotherapy alone in the treatment of patients with refractory pituitary adenomas. The Basic treatment was Radiotherapy, which is consisted of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday through Friday) over a period of six weeks, for a total dose of 54 Gy. The150 participants were randomized to use either radiotherapy plus Temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), or radiotherapy plus placebo for 6 weeks. After a 4-week break, patients were then to receive up to six cycles of adjuvant temozolomide or placebo according to the standard 5-day schedule every 28 days. The dose was 150 mg per square meter for the first cycle and was increased to 200 mg per square meter beginning with the second cycle, so long as there were no hematologic toxic effects followed by six cycles of placebo or adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was Objective Response rate, the second end point was PFS. Greater response was anticipated in patients treated with Temozolomide+ radiotherapy than radiotherapy alone.
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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Minimum Age: 18 Years Maximum Age: 80 Years
- •Age ≥18 years, regardless of gender;
- •Meet the diagnostic criteria for refractory pituitary tumors;
- •The tumor showed invasive growth on imaging and rapid growth, Ki-67 labeling index ≥3%;
- •The tumor recurred within a short period of time (< 6months) after total resection;
- •The tumor continues to grow after surgery and medical therapy;
- •Systemic examination showed no metastases in the cranial canal or other systems throughout the body.
- •Clinicopathological diagnosis of pituitary adenoma, and pathological tissue (wax or frozen tissue) can be obtained;
- •Expected survival time ≥ 6 months;
- •KPS score ≥70 points;
- •Subjects who were able to read, understand, and sign written informed consent prior to participating in the study and were willing to comply with protocol requirements.
排除标准
- •Participants cannot participate in this study if they meet any of the following conditions:
- •Subjects participated in clinical studies of other drugs or medical devices within 3 months before screening.
- •Known to be allergic to temozolomide capsules;
- •Have been diagnosed with pituitary carcinoma or have other malignant tumors;
- •Have received radiation therapy for Sella region;
- •Those with severe acute and chronic diseases in various systems, whose conditions have not been effectively controlled, and whose conditions are unstable, including but not limited to:
- •Patients with cardiac insufficiency (NYHA cardiac function grade ≥ 2), patients with severe heart disease such as cardiomyopathy, coronary heart disease, severe arrhythmia, etc. that are not effectively controlled;
- •Severe active infections,
- •Uncontrollable diabetes, hypertension / hypotension, cerebrovascular disease, gastric ulcer, respiratory disease, active autoimmune disease, etc .;
- •History of any other diseases that the researcher judges to be unsuitable for the trial, etc .;
- •For hepatic and renal insufficiency, hematological indicators: total bilirubin> 1.5 × ULN, ALT, AST> 2.5 × ULN; serum creatinine> 2 × ULN;
- •Those with a neutrophil count of less than 1.5 × 109 / L, or a platelet count of less than 100 × 109 / L, or an HGB of less than 90g / L;
- •Hepatitis B surface antigen, anti-HCV, anti-HIV or syphilis antibody positive;
- •Those who need to take valproic acid and drugs that can cause bone marrow depression during the application or research period;
- •pregnant or lactating women or those planning to become pregnant;
- •People with history of difficulty in drawing blood;
- •People with a history of bleeding disorders;
- •Subjects had a history of drug use or smoking and alcohol abuse within 6 months before enrollment;
- •Researchers do not consider it appropriate to participate in the trial.
研究组 & 干预措施
Radiotherapy plus temozolomide
Undergoing fractionated radiotherapy at a dose of 2 Gy per fraction given once daily five days per week for a total dose of 54 Gy, plus continuous daily temozolomide (75 mg per square meter of body-surface area per day), followed by six cycles of adjuvant temozolomide.
干预措施: Radiotherapy plus temozolomide (Drug)
Radiotherapy plus placebo
Radiotherapy treatment alone undergoing fractionated radiotherapy, total 54 Gy, 2GyX27, received placebo.
干预措施: Radiotherapy plus placebo (Other)
结局指标
主要结局
Tumor size
时间窗: Four weeks after concurrent chemoradiotherapy, patients were then to receive three cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. At the end of Cycle 3 (each cycle is 28 days)
A tumor response was defned as a decrease of more than 30% of the largest tumor diameter or stable in Tumor volume
次要结局
- Hormonal responses(Four weeks after concurrent chemoradiotherapy, patients were then to receive three cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. At the end of Cycle 3 (each cycle is 28 days))