A Phase III Trial of Adjuvant Chemotherapy Following Chemoradiation as Primary Treatment for Locally Advanced Cervical Cancer Compared to Chemoradiation Alone: The OUTBACK Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 926
- 试验地点
- 325
- 主要终点
- Overall Survival Rate at 5 Years
研究概览
简要总结
This randomized phase III trial studies how well giving cisplatin and radiation therapy together with or without carboplatin and paclitaxel works in treating patients with cervical cancer has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as cisplatin, carboplatin, and paclitaxel, work in different ways to stop the growth of [cancer/tumor] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. External radiation therapy uses high-energy x rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. It is not yet known whether giving cisplatin and external and internal radiation therapy together with carboplatin and paclitaxel kills more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemoradiation improves overall survival.
SECONDARY OBJECTIVES:
I. To determine the progression-free survival rates. II. To determine acute and long-term toxicities. III. To determine patterns of disease recurrence. IV. To determine the association between radiation protocol compliance and outcomes.
V. To determine patient quality of life, including psycho-sexual health.
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
- •Eligible patients will have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent, in addition to:
- •Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB1 & node positive, IB2, IIA, IIB, IIIB, or IVA disease
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix
- •White blood cells (WBC) >= 3.0 x 10^9/L
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- •Platelet count >= 100 x 10^9/L
- •Bilirubin =< 1.5 times upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x ULN (if both tests are done, both results need to be =< 2.5 x ULN)
- •Creatinine =< ULN (Common Toxicity Criteria [CTC] grade 0) OR calculated creatinine clearance (Cockcroft-Gault formula) >= 60 mL/min OR >= 50 mL/min by ethylenediaminetetraacetic acid (EDTA) creatinine clearance
- •Written informed consent
排除标准
- •Any previous pelvic radiotherapy
- •Para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if biopsy proven, PET positive, or >= 15 mm short-axis diameter on computed tomography [CT])
- •FIGO 2008 stage IIIA disease
- •Patients assessed at presentation as requiring interstitial brachytherapy treatment
- •Patients with bilateral hydronephrosis unless at least one side has been stented and renal function fulfills the required inclusion criteria
- •Previous chemotherapy for this tumor
- •Evidence of distant metastases
- •Prior diagnosis of Crohn's disease or ulcerative colitis
- •Peripheral neuropathy >= grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v]4)
- •Patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy; this includes patients with a prior history of supracervical hysterectomy
- •Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and in situ melanoma, who had (or have) any evidence of the other cancer present within the last 5 years
- •Patients who are pregnant or lactating
- •Any contraindication to the use of cisplatin, carboplatin, or paclitaxel chemotherapy
- •Serious illness or medical condition that precludes the safe administration of the trial treatment including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Patients who are known to be human immunodeficiency virus (HIV) positive
研究组 & 干预措施
Arm I (cisplatin, radiation therapy, brachytherapy)
Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.
干预措施: Brachytherapy (Radiation)
Arm I (cisplatin, radiation therapy, brachytherapy)
Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.
干预措施: Cisplatin (Drug)
Arm I (cisplatin, radiation therapy, brachytherapy)
Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.
干预措施: External Beam Radiation Therapy (Radiation)
Arm I (cisplatin, radiation therapy, brachytherapy)
Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.
干预措施: Quality-of-Life Assessment (Other)
Arm II (cisplatin, radiation therapy, brachytherapy, chemo)
Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Brachytherapy (Radiation)
Arm II (cisplatin, radiation therapy, brachytherapy, chemo)
Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour 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 II (cisplatin, radiation therapy, brachytherapy, chemo)
Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour 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 II (cisplatin, radiation therapy, brachytherapy, chemo)
Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: External Beam Radiation Therapy (Radiation)
Arm II (cisplatin, radiation therapy, brachytherapy, chemo)
Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour 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 II (cisplatin, radiation therapy, brachytherapy, chemo)
Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour 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)
结局指标
主要结局
Overall Survival Rate at 5 Years
时间窗: 5 years from study randomization
Estimate for probability of overall survival at 5 years by Kaplan-Meier method, where overall survival is defined as the time from randomization to time of death due to any cause or the date of last contact, whichever occurs first.
次要结局
- Number of Participants With Adverse Events (Grade 3 or Higher) in First Year(1 year after randomization)
- Progression-free Survival Rate at 5 Years(5 years from study randomization)
- Radiation Protocol Compliance(Average duration of 7 weeks)
- Quality of Life for Global Health Status(Baseline and 12 months)
- Patterns of Disease Recurrence(through study completion an average of 60 months)