Randomized Phase III Trial of Doxorubicin/Cisplatin/Paclitaxel and G-CSF Versus Carboplatin/Paclitaxel in Patients With Stage III &Amp; IV or Recurrent Endometrial Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,381
- 试验地点
- 643
- 主要终点
- Number of Participants Alive at Time of Last Follow-up.
研究概览
简要总结
This randomized phase III trial compares how well two different combination chemotherapy regimens (doxorubicin hydrochloride, cisplatin, and paclitaxel versus carboplatin and paclitaxel) work in treating patients with endometrial cancer that is stage III-IV or has come back (recurrent). Drugs used in chemotherapy such as doxorubicin hydrochloride, cisplatin, paclitaxel, and carboplatin, 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. It is not yet known which combination chemotherapy regimen is more effective in treating endometrial cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine if the combination of carboplatin and paclitaxel (TC) chemotherapy is therapeutically equivalent to the combination of doxorubicin (doxorubicin hydrochloride), cisplatin and paclitaxel (TAP) chemotherapy with regards to survival.
II. To determine if estrogen/progesterone receptor status provides prognostic information in patients treated with chemotherapy.
III. To assess whether combination TC chemotherapy is superior to combination TAP chemotherapy with regards to toxicity profile, specifically neurotoxicity and infection.
IV. To measure differences in patient-reported neurotoxicity and quality of life (QOL) among the regimens.
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
- •Patients must have primary stage III or stage IV or recurrent endometrial carcinoma whose potential for cure by radiation therapy or surgery alone or in combination is very poor; pathological confirmation and estrogen receptor (ER)/progesterone receptor (PR) status of the primary tumor is mandatory; however, the results do not need to be available prior to registration
- •Patients may not have received prior cytotoxic chemotherapy, including chemotherapy used for radiation sensitization; patients may have received prior radiation therapy, hormonal therapy, or therapy with biologic agents, but such therapies must be discontinued prior to entry on this study
- •Patients in whom both radiation and chemotherapy is planned must receive radiation prior to entry on this study; at least four weeks should have elapsed since completion of radiation therapy (RT) involving the whole pelvis or over 50% of the spine
- •Platelets >= 100,000/mcl
- •Granulocytes (absolute neutrophil count [ANC]) >= 1,500/mcl
- •Creatinine =< upper limit of normal (ULN) (Common Toxicity Criteria [CTC] grade 0) or calculated creatinine clearance (Jeliffe Formula) >= 60 ml/min
- •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limits of normal
- •Bilirubin =< institutional upper limits of normal
- •Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
- •Patients must have met the pre-entry requirements
- •Patients must have signed an approved informed consent and authorization permitting release of personal health information
排除标准
- •Patients with a concomitant malignancy other than non-melanoma skin cancer; with the exception of non-melanoma skin cancer, patients with a prior invasive malignancy who have been disease-free for < 5 years or who received prior chemotherapy for that malignancy
- •Patients in whom pathological confirmation and estrogen receptor (ER)/progesterone receptor (PR) status of the tumor is not obtainable
- •Patients for whom radiation therapy is planned during or after study chemotherapy prior to demonstrated progression
- •Patients with concomitant medical illness such as serious uncontrolled infection, uncontrolled angina, or serious peripheral neuropathy, which, in the opinion of the treating physician, make the treatments prescribed on this study unreasonably hazardous for the patient
- •Patients with third degree or complete heart block are not eligible unless a pacemaker is in place; patients on medications which alter cardiac conduction, such as digitalis, beta-blockers, or calcium channel blockers, or who have other conduction abnormalities or cardiac dysfunction may be placed on study at the discretion of the investigator
- •Patients with history of myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure or symptoms suspicious for congestive heart failure are not eligible unless a left ventricular ejection fraction in the past 6 months is documented to be 50% or greater; patients who have had a left ventricular ejection fraction (LVEF) (performed for any reason) of less than 50% in the past 6 months are ineligible
- •Patients whose circumstances will not permit study completion or adequate follow-up
- •Patients who are sensitive to E. coli-derived drug preparations
- •Patients with uterine carcinosarcoma or other non-epithelial uterine malignancies
研究组 & 干预措施
Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)
Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)
Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)
Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Filgrastim (Biological)
Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)
Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)
Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)
Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Pegfilgrastim (Biological)
Arm I (doxorubicin hydrochloride, cisplatin, paclitaxel)
Patients receive doxorubicin hydrochloride IV over approximately 15-30 minutes on day 1, cisplatin IV over 60-90 minutes on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm II (paclitaxel, carboplatin)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm II (paclitaxel, carboplatin)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (paclitaxel, carboplatin)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Arm II (paclitaxel, carboplatin)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 7 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 Alive at Time of Last Follow-up.
时间窗: Patients were assessed during treatment. Following completion of treatment, follow up was assessed every 3 months for 2 years, then every 6 months for 3 years and annually after for a maximum of 10 years.
The time alive in months from study entry to last contact or death.
次要结局
- Number of Participants With Indicated Severity of CTCAE v2 Graded Neurotoxicity and Infection(Assessed throughout the treatment period and for 30 days after discontinuation of treatment.)
- Patient Reported Quality of Life as Measured With the Combination of Physical Well-being (PWB) Subscale and Functional Well-being (FWB) Subscale From the FACT-G(Pre-treatment, 6 weeks post starting treatment (prior to cycle 3), 15 weeks post starting treatment (prior to cycle 6), 26 weeks post starting treatment)
- Number of Participants Alive at Time of Last Follow-up by Estrogen or Progesterone Receptor Status (Positive or Negative)(Patients were assessed during treatment. Following completion of treatment, follow up was assessed every 3 months for 2 years, then every 6 months for 3 years and annually thereafter, for a maximum of 10 years.)
- Patient-reported Neurotoxicity (Ntx) as Measured by the FACT/GOG-Ntx Subscale (Short)(Baseline, 6 weeks post treatment start, 15 weeks post treatment start and 26 weeks post treatment start)