NCT01672892已完成3 期
A Randomized Phase III Study of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer (TIME-C)
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 289
- 试验地点
- 137
- 主要终点
- Acute Gastrointestinal Toxicity, as Measured by Change in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score at 5 Weeks From the Start of Pelvic Radiation
研究概览
简要总结
RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.
PURPOSE: This randomized phase III trial is studying two different methods of radiation and their side effects and comparing how well they work in treating endometrial and cervical cancer after surgery.
详细描述
OBJECTIVES:
Primary
- To determine if pelvic intensity-modulated radiation therapy (IMRT) reduces acute gastrointestinal toxicity in the 5th week (after 23-25 fractions) of pelvic radiation as measured with the expanded prostate cancer index composite (EPIC) instrument.
Secondary
- To determine if grade 2+ gastrointestinal toxicity (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v. 4.0]) is reduced with IMRT compared to conventional whole-pelvis radiation therapy (WPRT).
- To determine if grade 2+ hematologic toxicity (CTCAE v. 4.0) is reduced with IMRT compared to conventional WPRT.
- To determine if urinary toxicity is reduced with IMRT using the EPIC urinary domain.
- To validate EPIC bowel and urinary domains in women undergoing either IMRT pelvic radiation treatment or four-field pelvic radiation treatment for endometrial or cervical cancer.
- To assess the impact of pelvic IMRT on quality of life using the Functional Assessment of Cancer Therapy-General (FACT-G) with cervix subscale.
- To determine if there is any difference in local-regional control, disease-free survival, and overall survival between patients treated with IMRT as compared to conventional WPRT.
- To perform a health-utilities analysis to measure the financial impact of pelvic IMRT via the EQ-5D instrument.
- To identify molecular predictors of radiation toxicity and novel circulating cancer biomarkers.
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
- •Pathologically proven diagnosis of endometrial or cervical cancer.
- •Patients must have undergone a hysterectomy (total abdominal hysterectomy, vaginal hysterectomy or radical hysterectomy or total laparoscopic hysterectomy) for carcinoma of the cervix or endometrium within 49 days prior to registration. Performance of a bilateral salpingooophorectomy will be at the treating surgeon's discretion.
- •Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
- •3.1 History/physical examination within 45 days prior to registration;
- •3.2 CT, MRI or positron emission tomography - computed tomography (PET-CT) including the abdomen and pelvis should be performed for initial radiological staging. This may be performed pre- or post-surgery within 90 days prior to registration. Imaging performed post-operatively should show no evidence of residual disease. Any evidence of malignancy identified on pre-operative imaging should have been completely resected surgically prior to protocol treatment.
- •3.3 Chest CT or chest x-ray must be performed within 90 days prior to registration (unless a PET-CT has been performed)
- •Zubrod Performance Status 0-2
- •Complete blood count (CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:
- •6.1 Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
- •6.2 Platelets ≥ 100,000 cells/mm3;
- •6.3 Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
- •For patients receiving chemotherapy:
- •7.1 Within 14 days prior to registration, serum creatinine ≤ 1.5 mg/dL and calculated creatinine clearance ≥ 50 cc/min. Both tests must be within these limits. The creatinine clearance should be calculated using the Cockcroft-Gault formula: (See Section 7.3.1) 7.2 Aspartate aminotransferase (AST) ≤ 2 x upper limit of normal (ULN) 7.3 Bilirubin ≤ 2 x ULN 7.4 Alkaline phosphatase, Mg, blood urea nitrogen (BUN) and electrolytes must be obtained and recorded 8 Endometrial Cancer: 8.1 Patients with the following histologic features are eligible for pelvic radiation therapy without weekly cisplatin:
- •<50% myometrial invasion, grade 3 adenocarcinoma without uterine serous carcinoma (USC) or clear cell histology
- •≥50% myometrial invasion grade 1-2 adenocarcinoma without USC or clear cell histology 8.2 Patients with the following histologic features may be treated with pelvic radiation with or without weekly cisplatin. The decision to add weekly cisplatin for these patients is at the treating physician's discretion:
- •≥50% myometrial invasion, grade 3 including USC and clear cell carcinoma.
- •International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrial cancer of any grade including USC and clear cell carcinoma.
- •FIGO 2009 IIIC1 (pelvic lymph node positive only, para-aortic nodes negative if removed) including USC and clear cell carcinoma. Note: If para-aortic nodes are not removed, CT abdomen or PET CT must demonstrate no evidence of lymphadenopathy.
- •Cervical Cancer: 9.1 Patients with the following pathology findings may be treated with pelvic radiation with or without weekly cisplatin at the treating physician's discretion. The decision to add weekly cisplatin for these patients is at the treating physician's discretion. 9.1.1 Patients with intermediate risk features including two of the following histologic findings after radical hysterectomy:
- •1/3 or more stromal invasion
- •Lymph-vascular space invasion
- •Large clinical tumor diameter (> 4 cm) 9.1.2 Patients with cervical cancer treated with a simple hysterectomy with negative margins 9.2 Patients with any of the following criteria following radical hysterectomy are eligible for this study and must receive weekly cisplatin:
- •Positive resected pelvic nodes and para-aortic nodes negative if removed. Note: If para-aortic nodes are not removed, CT abdomen or PET CT must demonstrate no evidence of lymphadenopathy.
- •Microscopic parametrial invasion with negative margins.
- •Patient must provide study specific informed consent prior to study entry.
- •Willingness and ability to complete the bowel and urinary domains of the EPIC prior to registration
排除标准
- •Patients with para-aortic nodal disease or who require extended field radiotherapy beyond the pelvis.
- •Patients with histology consisting of endometrial stromal sarcoma, leiomyosarcoma or malignant mixed mullerian mixed tumor (MMMT or carcinosarcoma)
- •Patients who exceed the weight/size limits of the treatment table or CT scanner.
- •Mental status changes or bladder control problems that make the patient unable to comply with bladder-filling instructions.
- •Patients with evidence of metastatic disease outside of the pelvis.
- •Patients with positive or close (< 3 mm) resection margins
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
- •Prior radiation therapy to the pelvis
- •Patients with active inflammatory bowel disease. 10 Severe, active co-morbidity, defined as follows:
- •10.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- •10.2 Transmural myocardial infarction within the last 6 months
- •10.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- •10.4 Other major medical illness which requires hospitalization or precludes study therapy at the time of registration
- •10.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however,that laboratory test coagulation parameters are not required for entry into this protocol
- •10.6 Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients.
- •Patients with prior treatment with platinum-based chemotherapy
- •Women who are breastfeeding
研究组 & 干预措施
Intensity-Modulated Radiation Therapy
Experimental
intensity-modulated radiation therapy (IMRT) to the pelvis of either 45 Gy or 50.4 Gy
干预措施: Standard radiation therapy (Radiation)
Standard Radiation Therapy
Active Comparator
Standard radiation therapy (4-field) to the pelvis of either 45 Gy or 50.4 Gy
干预措施: intensity-modulated radiation therapy (Radiation)
结局指标
主要结局
Acute Gastrointestinal Toxicity, as Measured by Change in Expanded Prostate Cancer Index Composite (EPIC) Bowel Domain Score at 5 Weeks From the Start of Pelvic Radiation
时间窗: Baseline and week 5 of RT
The primary endpoint is change in acute GI toxicity, as measured by the EPIC bowel domain, from baseline to 5 weeks after the first fraction of radiation is delivered. The EPIC has four domains (bowel, urinary, sexual, and hormonal) that have been validated separately, which allows use of only the domains of interest. The EPIC bowel domain consists of 14 items and has a function subscale (7 items) and bother subscale (7 items). For each domain, responses form a Likert scale and multi-item scale scores are transformed linearly to a 0-100 scale, where higher scores correspond to better quality of life. At least 80% of the items in a domain or subscale of the domain must be completed in order to compute the score. Change was calculated as follow-up score - baseline score so a negative change score indicates a decline in function.
次要结局
- Mean Change From Baseline in EPIC Bowel and Urinary Domain (Validation - Sensitivity to Treatment)(Baseline and week 5 of RT)
- Urinary Toxicity, as Measured by Change in EPIC Urinary Domain(Baseline, week 3 and 5 of RT, and 4-6 weeks after RT)
- Overall Survival(From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.)
- Identification of Molecular Predictors of Radiation Toxicity and Novel Circulating Cancer Biomarkers(Outcome measure will not be analyzed)
- Spearman's Correlation Coefficient for EPIC Bowel Domain vs. Urinary Domains (Validation - Conceptual Independence)(Baseline and week 5 of RT)
- Pearson Correlation Coefficient for EPIC Bowel and Urinary Domains vs. FACT-G Total Score (Validation - Criterion Validity)(Baseline and week 5 of RT)
- Quality of Life, as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Cx (Cervix) Subscale(Before study start, Week 5 of RT, 4-6 Weeks after RT, 1 year from start of RT and 3 years from start of RT)
- Health Utilities, as Measured by Change From Baseline in EQ-5D(Baseline, week 5 of RT, 4-6 weeks after RT)
- Percentage of Patients With Acute Grade 2+ GI Toxicity at 5 Weeks From the Start of Treatment(Baseline to Week 5 of RT)
- Disease-free Survival(From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.)
- Local-regional Recurrence(From randomization to last follow-up. Maximum follow-up at time of analysis was 37.8 months.)
- Standardized Cronbach's Alpha for EPIC Bowel and Urinary Domains (Validation - Internal Consistency Reliability)(Baseline and week 5 of RT)
研究者
研究点 (137)
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