A Pilot Phase II Two-Arm, Randomized Clinical Trial of Concomitant Immunotherapy (With Interferon-Alpha and Retinoic Acid) and Radiation Therapy for the Treatment of Advanced Cervical Cancer in India
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 209
- 试验地点
- 1
- 主要终点
- Survival
研究概览
简要总结
The study objective:
- To evaluate the response and survival rates after treating stage III cervical cancer with retinoic acid and interferon-α combined with radiotherapy in the study group.
- To evaluate the response and survival rates after treating stage III cervical cancer patients with concomitant cisplatin and radiotherapy in the control group.
- To evaluate the safety and tolerability of the combination of retinoic acid, interferon-α and radiation therapy compared with concomitant chemo-radiation therapy.
- To determine if there is an immune response to Human Papillomavirus (HPV) by estimating serum IgG1 and IgG2 antibodies against E7 proteins of HPV types 16 and 18 before and after treatment.
The study hypothesis:
- The response rates and survival rates of retinoic acid and interferon-α combination with radiation will be better than chemo-radiation to treat stage III cervical cancer.
- Treatment with the retinoic acid, interferon-α and radiation combination therapy will be less toxic and better tolerated than chemo-radiation therapy.
详细描述
A total of 200 women with confirmed diagnosis of invasive cervical cancer, stage III, will be recruited into the study. The patients will be recruited from the Gynecologic Oncology Department of the Chittaranjan National Cancer Institute that registers more than 600 cases of cancer of the cervix per year. Computer-generated numbers will randomize patients into the two treatment arms.
This trial is designed to treat stage III cervical cancer patients with concomitant immunotherapy (with cis-retinoic acid and interferon-α) and radiotherapy in the study arm.
Cancer of the uterine cervix is the second most common cancer among women worldwide and is the cause of the largest number of cancer-related deaths among women in the developing countries. In India, cervical cancer is the commonest cancer among women (126,000 new cases, 71,000 deaths in 2000), accounting for more than a quarter of the global burden of cervical cancer (471,000 new cases and 233,000 deaths).1,2 In contrast, in the U.S., although, there were only 12,200 new cases of cervical cancer and 4,100 deaths in 2003, the United States spends $5 billion per year screening and treating cervical cancer and precancerous lesions.
Advanced cervical cancer is relatively rare in the developed world because of routine PAP testing. However, in a developing country like India, because of the absence of any population based cervical cancer screening programs (HPV testing, PAP smears), nearly 80% of the patients are initially detected at stage III or higher. Cisplatin-based chemotherapy administered along with surgery and radiation is the recommended treatment for advanced cervical cancer in the US and other developed countries.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Advanced cervical cancer
排除标准
- •Previously treated for cancer of the cervix
- •Karnofsky Performance Score less than 50
- •Renal dysfunction ( Serum creatinine > 2.0mg/dl)
- •Hepatic dysfunction (Serum bilirubin> 2.0 mg/dl, transaminases > 1.5 times normal)
- •Pregnant or lactating women: Women will be tested by pregnancy test for possibility of existing pregnancy. Those that meet criteria of trial will be asked to promise that they don't become pregnant; barrier contraception will be recommended.
研究组 & 干预措施
Group A
Treatment consists of Interferon, given as a sub-cutaneous injection, 3 times per week for 4 weeks, 20 mg Retinoic Acid tablets, 2 times a day for 30 days. starting from the first day of radiation.
干预措施: Interferon, Retinoic Acid and radiation (Drug)
Group B
Treatment consists of radiation and chemotherapy using Cisplatin. Cisplatin, given intravenously, will be administered on the first day of each week, mixed with saline solution, before and after the Cisplatin infusion.
Radiation will be given for a few minutes daily, five days a week, for approximately 5 weeks.
Two weeks after completion of external radiotherapy, subject will receive internal radiation (brachytherapy) once a week for two weeks. For this internal radiation a specially designed instrument will be inserted into the vagina that will be connected to a machine for a few minutes.
干预措施: Cisplatin and radiation (Drug)
结局指标
主要结局
Survival
时间窗: 3 years or death
Overall survival curves will be computed using the method of Kaplan and Meyer. The difference in survival between the two groups will be compared by log rank test with the O'Brien-Fleming boundaries to control for alpha spending at a planned interim analysis (50% of the total accrual).
次要结局
- Response rate(3 years or death)
- Overall toxicity(3 years or death)
- Determine immune response to Human Papillomavirus HPV(3 years to death)