A Randomized Phase III Trial of Cisplatin and Tumor Volume Directed Irradiation Followed by Carboplatin and Paclitaxel vs. Carboplatin and Paclitaxel for Optimally Debulked, Advanced Endometrial Carcinoma
试验速览
- 阶段
- 3 期
- 入组人数
- 813
- 试验地点
- 666
- 主要终点
- Number of Participants With Recurrence, Progression or Death
研究概览
简要总结
This randomized phase III trial studies carboplatin and paclitaxel to see how well they work with or without cisplatin and radiation therapy in treating patients with stage I-IVA endometrial cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether carboplatin and paclitaxel are more effective with or without cisplatin and radiation therapy in treating patients with endometrial cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (experimental arm) reduces the rate of recurrence or death (i.e., increases recurrence-free survival) when compared to chemotherapy consisting of carboplatin and paclitaxel for 6 cycles (control arm) in patients with stages III-IVA endometrial carcinoma (< 2 cm residual disease) or patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I or II serous (uterine papillary serous carcinoma [UPSC]) or clear cell endometrial carcinoma and positive cytology.
SECONDARY OBJECTIVES:
I. To determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (experimental arm) reduces the rate of death (i.e., increases survival) when compared to chemotherapy consisting of carboplatin and paclitaxel for 6 cycles (control arm) in patients with stages III-IVA endometrial carcinoma (< 2 cm residual disease) or patients with FIGO 2009 stage I or II serous (UPSC) or clear cell endometrial carcinoma and positive cytology.
II. To compare the regimens with respect to acute and late adverse effects of therapy.
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
- •All patients with surgical stage III or IVA endometrial carcinoma per FIGO 2009 staging criteria including clear cell and serous papillary and undifferentiated carcinoma
- •Surgical stage III disease includes those patients with positive adnexa, parametrial involvement, tumor invading the serosa, positive pelvic and/or para-aortic nodes, or vaginal involvement
- •Surgical stage IVA patients with bladder or bowel mucosal involvement, but no spread outside the pelvis
- •Patients with FIGO 2009 surgical stage I or II endometrial clear cell or serous carcinoma and with positive peritoneal cytology
- •Surgery must have included a hysterectomy and bilateral salpingo-oophorectomy; pelvic lymph node sampling and para-aortic lymph node sampling are optional
- •Patients with a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
- •White blood cell (WBC) >= 3,000/mcl
- •Absolute neutrophil count (ANC) >= 1,500/mcl
- •Platelet count >= 100,000/mcl
- •Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN)
- •Alkaline phosphatase =< 2.5 times ULN
- •Bilirubin =< 1.5 times ULN
- •Creatinine =< institutional ULN
- •Patients who have met the pre-entry requirements; testing values/results must meet eligibility criteria
- •Patients who have signed an approved informed consent and authorization permitting release of personal health information
- •Entry into the study is limited to no more than 8 weeks from the date of surgery
排除标准
- •Patients with carcinosarcoma
- •Patients with recurrent endometrial cancer
- •Patients with residual tumor after surgery (any single site) exceeding 2 cm in maximum dimension
- •Patients who have had pelvic or abdominal radiation therapy
- •Patients with positive pelvic washings as the only extra-uterine disease are NOT eligible if the histology is other than clear cell or papillary serous carcinoma
- •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of active malignancy within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
- •Patients with a history of serious co-morbid illness or uncontrolled illnesses that would preclude protocol therapy
- •Patients with an estimated survival of less than three months
- •Patients with FIGO 2009 stage IVB endometrial cancer
- •Patients with parenchymal liver metastases
- •Patients who have received prior chemotherapy for endometrial cancer
- •Patients with a history of myocardial infarction, unstable angina, or uncontrolled arrhythmia within 3 months from enrollment
研究组 & 干预措施
Arm I (cisplatin, radiation therapy, paclitaxel, carboplatin)
Patients receive cisplatin IV on days 1 and 29. Patients also undergo radiation therapy QD, 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm I (cisplatin, radiation therapy, paclitaxel, carboplatin)
Patients receive cisplatin IV on days 1 and 29. Patients also undergo radiation therapy QD, 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Arm I (cisplatin, radiation therapy, paclitaxel, carboplatin)
Patients receive cisplatin IV on days 1 and 29. Patients also undergo radiation therapy QD, 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Internal Radiation Therapy (Radiation)
Arm I (cisplatin, radiation therapy, paclitaxel, carboplatin)
Patients receive cisplatin IV on days 1 and 29. Patients also undergo radiation therapy QD, 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Arm I (cisplatin, radiation therapy, paclitaxel, carboplatin)
Patients receive cisplatin IV on days 1 and 29. Patients also undergo radiation therapy QD, 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm I (cisplatin, radiation therapy, paclitaxel, carboplatin)
Patients receive cisplatin IV on days 1 and 29. Patients also undergo radiation therapy QD, 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy (Radiation)
Arm II (paclitaxel and carboplatin)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm II (paclitaxel and carboplatin)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Arm II (paclitaxel and carboplatin)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Number of Participants With Recurrence, Progression or Death
时间窗: Disease was to be assessed at baseline, end of treatment and every 6 months for two years, and annually up to 5 years.
Number of participants enrolled with recurrence or progression of disease or death up to date of last contact. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions.
次要结局
- Number of Participants With Acute Adverse Effects as Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version (CTCAE) Version 3.0(Assessed throughout the treatment period and for 21-30 days after discontinuation of treatment)
- Number of Participants With Late Adverse Events as Graded by the NCI CTCAE Version 3.0(Assessed every 6 months for 3 years)
- Overall Survival(From entry into the study to death or the date of last contact, assessed up to 8 years)
- Patient-reported Peripheral Neuropathy Symptoms(Prior to study treatment (baseline), Arm 1: 1 week post completion of radiation therapy, Arm 2: Prior to cycle 3 (6 weeks post starting of study treatment), 18 weeks post the starting of study treatement, 70 weeks post the starting of study treatment)
- Patient-reported Quality of Life (QOL)(Prior to study treatment (baseline), Arm 1: 1 Week post completion of radiation therapy, Arm 2: Prior to cycle 3 (6 weeks post starting of study treatment), 18 weeks post the starting of study treatment, 70 weeks post the starting of study treatment)