A Phase III Trial of Pelvic Radiation Therapy Versus Vaginal Cuff Brachytherapy Followed by Paclitaxel/Carboplatin Chemotherapy in Patients With High Risk, Early Stage Endometrial Carcinoma
试验速览
- 阶段
- 3 期
- 入组人数
- 601
- 试验地点
- 538
- 主要终点
- Number of Participants With Recurrence or Death Events at Primary Analysis
研究概览
简要总结
This randomized phase III trial studies pelvic radiation therapy to see how well it works compared with vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with high-risk stage I or stage II endometrial cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Implant radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Drugs used in chemotherapy, such as 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 whether pelvic radiation therapy alone is more effective than vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with endometrial cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine if treatment with vaginal cuff brachytherapy followed by three cycles of chemotherapy reduces the rate of recurrence or death (i.e. increases recurrence-free survival) when compared to pelvic radiation therapy.
SECONDARY OBJECTIVES:
I. To compare survival between the two treatment groups. II. To compare patterns of failure between the two treatment groups. III. To compare physical functioning, fatigue and neurotoxicity between the two treatment groups.
IV. To examine associations between primary comorbid illnesses and obesity on survival, fatigue and physical functioning.
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
- •To be considered eligible to participate in this trial, all patients must have undergone hysterectomy; bilateral salpingo-oophorectomy (open or laparoscopic approach) is strongly encouraged
- •Peritoneal cytology should be obtained on entering the peritoneal cavity, as described in the Gynecologic Oncology Group (GOG) Surgical Procedures Manual (https://gogmember.gog.org/manuals/pdf/surgman.pdf); pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged (as staged patients enrolled on GOG-0210-molecular markers in endometrial carcinoma are eligible for this study)
- •The procedures may be performed via laparotomy or laparoscopy (including robot-assisted) as per the surgeon?s preference; the surgeon must record in the operative report whether a lymphadenectomy was performed (see link above to Surgical Procedures Manual) or not; a specific number of lymph nodes removed will not be utilized for eligibility, but the operative report should reflect that the procedure performed was consistent with the procedures described in the GOG Surgical Manual
- •If either a bilateral salpingo-oophorectomy or nodal dissection was not performed, post-operative pre-treatment computed tomography (CT)/magnetic resonance imaging (MRI) is required and must not demonstrate evidence suggestive of metastatic disease (adnexa, nodes, intraperitoneal disease); post-operative, pre-treatment CT/MRI must be performed if a pelvic and para-aortic nodal dissection was not performed
- •For the purposes of description, patients will be staged according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system; eligibility is defined based on clinical-pathologic features; patients with endometrial carcinoma (endometrioid types) confined to the corpus uteri or with endocervical glandular involvement fitting one of the following high-intermediate risk factor categories:
- •Age >= 70 years with one risk factor
- •Age >= 50 with 2 risk factors
- •Age >= 18 years with 3 risk factors
- •Risk factors: grade 2 or 3 tumor, (+) lymphovascular space invasion, outer ? myometrial invasion; patients with these risk criteria may be enrolled with either positive or negative cytology
- •Patients with stage II endometrial carcinoma (any histology) with cervical stromal invasion (occult or gross involvement), with or without high-intermediate risk factors
- •Patients with serous or clear cell histology (with or without other high-intermediate risk factors) are eligible provided the disease is uterine-confined (with or without cervical stromal invasion or endocervical glandular involvement), and with peritoneal cytology negative for malignancy
- •Patients must have GOG performance status 0, 1, or 2
- •Absolute neutrophil count (ANC) >= 1,500/mcl (equivalent to Common Toxicity Criteria [CTCAE version [v] 3.0] grade 1)
- •Platelets >= 100,000/mcl (CTCAE v3.0 grade 0-1)
- •Serum creatinine =< institutional upper limit normal (ULN), CTCAE v 3.0 grade 0
- •Note: If serum creatinine > ULN, a 24-hour creatinine clearance must be collected and must be > 50 mL/min
- •Bilirubin =< 1.5 x ULN (CTCAE v3.0 grade 1)
- •Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x ULN (CTCAE grade 0-1)
- •Alkaline phosphatase =< 2.5 x ULN (CTCAE grade 0-1)
- •Neuropathy (sensory and motor) =< CTCAE v3.0 grade 1
- •Patients who have met the pre-entry requirements; testing values/results must meet eligibility criteria
- •Patients must have signed an approved informed consent and authorization permitting release of personal health information
排除标准
- •Patients who have already received non-surgical therapy for endometrial cancer including chemotherapy, radiation (example, pre-operative or post-operative brachytherapy), hormonal or biologic therapy
- •Patients identified with pathologically confirmed spread of cancer beyond the uterus and cervix to pelvic or para-aortic lymph nodes, adnexal structures, and/or other anatomic sites, or patients with serous or clear cell histology and with positive cytologic washings
- •Patients with nodal (for patients who did not have nodal dissection performed) or distant disease determined based on imaging studies; patients with suspicious nodes that have been biopsied (re-staging operation, fine needle aspiration [FNA]) and are pathologically negative will be eligible
- •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last 5 years; patients are excluded if their previous cancer treatment contraindicates this protocol therapy; specifically, patients who have received prior radiotherapy directed to treat disease within the abdominal cavity or pelvis are excluded
- •Prior radiation of localized cancer of the breast, head and neck, thyroid, or skin is permitted, provided that it was completed more than 5 years prior to registration, and the patient remains free of recurrent or metastatic disease
- •Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than 5 years prior to registration, and the patient remains free of recurrent or metastatic disease
- •Patients who have contraindications to pelvic radiation therapy (RT) (e.g. pelvic kidney, connective tissue disease, inflammatory bowel disease, etc.) should be screened in advance and not be considered eligible for the trial
- •Patients with recurrent endometrial cancer
- •Patients with surgical or clinical, FIGO 2009 stage III or IV endometrial carcinoma
- •Patients with non-epithelial uterine malignancies such as uterine carcinosarcoma or leiomyosarcoma
研究组 & 干预措施
Arm I (pelvic radiation therapy)
Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Arm I (pelvic radiation therapy)
Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Arm I (pelvic radiation therapy)
Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
干预措施: Internal Radiation Therapy (Radiation)
Arm I (pelvic radiation therapy)
Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (pelvic radiation therapy)
Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
干预措施: Quality-of-Life Assessment (Other)
Arm I (pelvic radiation therapy)
Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
干预措施: Questionnaire Administration (Other)
Arm II (brachytherapy, paclitaxel, carboplatin)
Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm II (brachytherapy, paclitaxel, carboplatin)
Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Internal Radiation Therapy (Radiation)
Arm II (brachytherapy, paclitaxel, carboplatin)
Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (brachytherapy, paclitaxel, carboplatin)
Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Arm II (brachytherapy, paclitaxel, carboplatin)
Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm II (brachytherapy, paclitaxel, carboplatin)
Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Number of Participants With Recurrence or Death Events at Primary Analysis
时间窗: Within 4 weeks after completing or discontinuing study therapy, then every 6 months for 2 years, then annually for 3 years, then as clinically indicated, assessed up to 10 years
Recurrence-Free Survival is the period from study entry until disease recurrence, death, or date of last contact
次要结局
- Patient-reported Quality of Life(Prior to study treatment (baseline), 4 weeks post the starting of study treatment, 10-11 weeks post the starting of study treatment, 8 months post the starting of study treatment, 14 months post the starting of study treatment)
- Number of Participants With Death Events(Overall survival is measured from study enrollment for up to 10 years.)
- Number of Participants With Sites of Recurrence(Within 4 weeks after completing or discontinuing study therapy, then every 6 months for 2 years, then annually for 3 years, then as clinically indicated thereafter, up to 10 years)
- Patient Reported Fatigue(Prior to study treatment (baseline), 4 weeks post the starting of study treatment, 10-11 weeks post the starting of study treatment, 8 months post the starting of study treatment, 14 months post the starting of study treatment)
- Patient-reported Neurotoxicity(Prior to study treatment (baseline), 4 weeks post the starting of study treatment, 10-11 weeks post the starting of study treatment, 8 months post the starting of study treatment, 14 months post the starting of study treatment.)