Pirfenidone Versus Placebo as Prophylaxis Against Acute Radiation-induced Lung Injury Following Hypofractionated Radiotherapy in Breast Cancer Patients (PRILI): A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study Evaluating
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Changes in lung injury grading on chest computerized tomography within 3 months after radiotherapy
研究概览
简要总结
The incidence of chest CT manifestations of lung injury after radiotherapy for breast cancer is more than 50%. Although the prognosis and quality of life of patients are rarely affected, it is still necessary to prevent the occurrence of minor radiation lung injury with the use of more novel drugs and subsequent salvage treatment may aggravate the radiation injury. This study intends to conduct a randomized, double-blind, single-center clinical study of pirfenidone versus placebo in the prevention of acute radiation induced lung injury after breast cancer surgery
详细描述
The incidence of chest CT manifestations of lung injury after radiotherapy for breast cancer is more than 50%. Although the prognosis and quality of life of patients are rarely affected, it is still necessary to prevent the occurrence of minor radiation lung injury with the use of more novel drugs and subsequent salvage treatment may aggravate the radiation injury. This study intends to conduct a randomized, double-blind, single-center clinical study of pirfenidone versus placebo in the prevention of acute radiation induced lung injury after breast cancer surgery.In this study, the incidence of grade 1-4 radiation lung injury was expected to be 60% in the radiotherapy alone group (placebo group), and pirfenidone capsules (experimental group) were expected to reduce the incidence of lung injury after radiotherapy to 40%. Bilateral test showed a statistical efficacy of 0.8 (α option 0.05). In this study, two independent rate comparison sample sizes were used to calculate, Binomial Enumeration method was used for 97 patients in both groups, and the expected shedding rate was 10%. 107 patients were needed in each group, and the total sample size was 214. Biological specimens are expected to be obtained from more than 100 patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
The biostatistician (Chen Jinhua), who is not related to the statistical analysis of the data management performed in this experiment, used statistical software on the computer to generate random number tables by simple randomization according to the ratio of 1:1 between the experimental group and the control group. According to the existing random number table, the drug was coded by personnel unrelated to this study under the supervision of the clinical trial institution of the unit, and the random number and drug number assigned by the researcher according to the order of case enrollment were administered. The random number table and drug code are sealed together in the blind base as confidential data, and the blind base is kept in two sealed copies in the drug clinical research institution of the sponsor and the main investigator
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •To be enrolled in this study, patients must meet all of the following inclusion criteria:
- •Breast invasive carcinoma or ductal carcinoma in situ or lobular carcinoma in situ confirmed by histology;
- •Age 18-75, female;
- •The physical state score of the Eastern Tumor Cooperative Group (ECOG) was 0-2;
- •Patients meeting the indications of postoperative radiotherapy and neoadjuvant chemotherapy: clinical stage 3 or above or postoperative ypT3-T4 or N+; Non-neoadjuvant chemotherapy patients: postoperative pathological staging of pT3-T4 or pN2 or above, or positive for upper and lower clavicle and lymph nodes in the internal milk region, or positive for clinical consideration; For patients with pT1-2N1, postoperative adjuvant radiotherapy should be determined based on the patient's age, tumor grade, incisal margin, number of positive lymph nodes, molecular typing, past complications, and patient's intention.
- •Radiotherapy regimen was chest wall + supraclavicular 40Gy/15f after root modification, or whole milk ± upper and lower clavicular 40Gy/15f after breast preservation, tumor bed simultaneous supplement 50Gy/15f;
- •All screening period laboratory tests should be performed in accordance with protocol requirements and within 28 days prior to enrollment. The values of laboratory tests performed by screening must meet the following criteria:
- •blood routine check all meet the following criteria: A. Hb≥90g/L; B. ANC≥1.5×109/L; C. PLT≥70×109/L; biochemical examination all meet the following criteria: TBIL < 1.5× upper limit of normal range (ULN); ALT and AST≤2.5 x ULN; Serum Cr≤1.25×ULN or endogenous creatinine clearance ≥45 mL/min (Cockcroft-Gault formula)
- •Women who are at risk of becoming pregnant must undergo a negative serum pregnancy test within 7 days before the first dose and be willing to use a highly effective method of contraception during the trial period and 120 days after the last dose of the test drug. Male subjects with a partner of a woman of reproductive age should be surgically sterilized or consent to a highly effective method of contraception during the trial period and 120 days after the last test drug administration;
- •The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up.
排除标准
- •Patients with any of the following criteria were not enrolled in this study
- •History and complications A. male breast cancer patients; B. Did not meet the conditions of large segmentation radiotherapy (upper and lower clavicular lymph node metastasis, internal milk lymph node metastasis, the patient refused large segmentation radiotherapy); C. The subject has any active, known, or suspected autoimmune disease. To admit subjects who are in a stable state and do not require systemic immunosuppressive therapy; D. The patient is participating in another clinical study or less than 4 weeks after the end of the previous clinical study; E. Patients with a known or highly suspected history of interstitial pneumonia; Or may interfere with the detection or management of suspected drug-related pulmonary toxicity; F. A history of other malignant tumors; Except in patients who have had potentially curable therapy and have not had disease recurrence for 5 years since treatment began; G. Pregnant women and patients with mental illness; H. Prior treatment with radiotherapy, chemotherapy, etc.; I. Patients with active tuberculosis should be excluded; J. Severe acute or chronic lung infections requiring systemic treatment; K. Patients with obvious blood coughing or daily hemoptysis of half a teaspoon (2.5ml) or more in the 2 months before randomization; L. Patients with heart failure (New York Heart Association standard Class III or IV), poor coronary artery disease control or arrhythmia, or a history of myocardial infarction in the 6 months prior to screening despite receiving appropriate medication.
- •Physical examination and laboratory examination A. A known history of testing positive for human immunodeficiency virus (HIV) or a known history of acquired immunodeficiency syndrome (AIDS); B. untreated active hepatitis (hepatitis B: HBsAg positive with HBV DNA≥ 500 IU/mL; Hepatitis C: HCV RNA positive and abnormal liver function); Combined with hepatitis B and hepatitis C co-infection.
- •As determined by the investigator, the patient may have other factors that may lead to the termination of the study, such as other serious diseases or serious abnormalities in laboratory tests or other factors that may affect the safety of the subjects, or family or social factors such as the collection of test data and samples.
研究组 & 干预措施
Pirfenidone
Patients were given placebo or pirfenidone capsules orally one week before radiotherapy, 200mg/ time, 3 times a day in the first week; 300mg/ time 3 times daily for the second week and 400mg/ time 3 times daily for the third to eighth week. Take it after a meal.
干预措施: Pirfenidone/Placebo (Drug)
Placebo
Patients were given placebo or pirfenidone capsules orally one week before radiotherapy, 200mg/ time, 3 times a day in the first week; 300mg/ time 3 times daily for the second week and 400mg/ time 3 times daily for the third to eighth week. Take it after a meal.
干预措施: Pirfenidone/Placebo (Drug)
结局指标
主要结局
Changes in lung injury grading on chest computerized tomography within 3 months after radiotherapy
时间窗: 4 weeks and 12 weeks after radiotherapy
Kouloulias scale was used to evaluate the changes of lung injury grading in chest computerized tomography within 3 months after radiotherapy. The higher the grading is, the more serious the lung injury is
次要结局
- Relationship between biomarkers and radioactive damage(1 week before medication，4 weeks and 12 weeks after radiotherapy)
- Relationship between biomarkers and therapy(1 week before medication，4 weeks and 12 weeks after radiotherapy)
- security(Every week of the medication，4 weeks and 12 weeks after radiotherapy)
研究者
Yong Yang
Chief physician
Fujian Medical University Union Hospital