Phase II/III Clinical Trial of Intensity Modulated Radiation Therapy With Concurrent Cisplatin for Stage I-IVA Cervical Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 7
- 主要终点
- Primary Event (Acute Hematologic or GI Toxicity)
研究概览
简要总结
The purpose of this study is to find out whether patients with cervical cancer treated with PET-guided Bone Marrow Sparing IMRT have less side effects with equal cancer control compared to standard radiation techniques (IMRT). The hypothesis is that PET-guided Bone Marrow Sparing IMRT will reduce acute hematologic and gastrointestinal toxicity and increase chemotherapy tolerance for cervical cancer patients treated with concurrent cisplatin.
详细描述
Multiple randomized controlled trials have established concurrent cisplatin-based chemoradiotherapy as the standard of care for locally advanced cervical cancer [3-8]. The addition of concurrent cisplatin to radiotherapy (RT) increases pelvic control, disease-free survival (DFS) and overall survival; however, 5-year DFS and overall survival are still only approximately 60% and 5-year pelvic failure is approximately 30%. Moreover, acute gastrointestinal (GI) and hematologic toxicity are increased. Approximately 30% of patients will experience acute grade ≥ 3 toxicity, predominantly GI and hematologic. Methods to reduce toxicity during chemoradiotherapy, particularly gastrointestinal and hematologic, could mitigate this toxicity and take advantage of the therapeutic benefits of intensive concurrent chemotherapy.
Intensity modulated radiation therapy (IMRT) is a modern RT technique that differs from conventional techniques in many ways. First, patients undergo computed tomography (CT) simulation so that customized target volumes can be defined 3-dimensionally. IMRT treatment planning involves multiple beam angles and uses computerized inverse treatment planning optimization algorithms to identify dose distributions and intensity patterns that conform dose to the target, reducing radiation dose to surrounding tissues. IMRT delivery is typically accomplished with the use of multileaf collimators, which involve small motorized leaflets (collimators) that move in and out of the beam path, modulating the dose intensity.
PET-guided Bone Marrow Sparing IMRT is designed to spare hematopoietically active subregions of the pelvic bone marrow using quantitative image segmentation. Previous studies indicate this approach can reduce toxicity and improve chemotherapy tolerance, which may improve outcomes and help optimized delivery of cytotoxic chemotherapy.
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
- •Biopsy-proven, invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
- •Biopsy result positive for carcinoma within 60 days prior to registration
- •FIGO clinical stage I-IVA disease, based on standard diagnostic workup, including:History/physical examination and/or Examination under anesthesia (if indicated)
- •If the patient is status post hysterectomy, one or more of the following conditions must be present: positive lymph nodes, positive margins, parametrial invasion, or non-radical surgery (i.e., simple hysterectomy).
- •If the patient is inoperable, one or more of the following conditions must be present: clinical stage IB2-IVA, positive lymph nodes on nodal sampling or frozen section, and/or parametrial invasion
- •Within 42 days prior to registration, the patient must have any of the following, if clinically indicated: examination under anesthesia, cystoscopy, sigmoidoscopy, rigid proctoscopy, or colonoscopy.
- •X-ray (PA and lateral), CT scan, or PET/CT scan of the chest within 42 days prior to registration;
- •CT scan, MRI, or PET/CT of the pelvis within 42 days prior to registration;
- •Karnofsky Performance Status 60-100
- •Absolute neutrophil count (ANC) ≥ 1500 cells/mm3; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable); Creatinine clearance ≥ 50 mg/dl; Bilirubin < 1.5 mg/dl; WBC ≥ 3,000/μl; ALT/AST < 3 x ULN; INR ≤ 1.5
- •Negative serum pregnancy test for women of child-bearing potential
排除标准
- •Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years;
- •Prior systemic chemotherapy within the past three years
- •Prior radiotherapy to the pelvis or abdomen that would result in overlap of radiation therapy fields;
- •Para-aortic, inguinal, or gross (unresected) pelvic nodal metastasis. Gross pelvic nodal metastasis is defined as either: Radiographic evidence of nodal metastasis on CT or MRI (node having short axis diameter > 1 cm)OR Radiographic evidence of nodal metastasis on diagnostic FDG-PET or PET/CT scan (abnormally increased FDG uptake as determined and documented by the radiologist)OR Biopsy-proven metastasis (e.g. needle biopsy) in undissected node
- •Distant metastasis
- •Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
- •Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- •Uncontrolled diabetes, defined as diabetes mellitus, which in the opinion of any of the patient's physicians requires an immediate change in management;
- •Uncompensated heart disease or uncontrolled high blood pressure
- •Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition
研究组 & 干预措施
IMRT with concurrent cisplatin 40 mg/m2
Intensity-modulated Radiation Therapy (IMRT) with concurrent cisplatin 40 mg/m2
干预措施: Cisplatin (Drug)
IMRT with concurrent cisplatin 40 mg/m2
Intensity-modulated Radiation Therapy (IMRT) with concurrent cisplatin 40 mg/m2
干预措施: IMRT (Radiation)
PET-guided Bone Marrow-Sparing IMRT
PET-guided Bone Marrow-Sparing IMRT with concurrent cisplatin 40 mg/m2
干预措施: PET-guided Bone Marrow-Sparing Intensity Modulated Radiation Therapy (IMRT) (Radiation)
PET-guided Bone Marrow-Sparing IMRT
PET-guided Bone Marrow-Sparing IMRT with concurrent cisplatin 40 mg/m2
干预措施: Cisplatin (Drug)
结局指标
主要结局
Primary Event (Acute Hematologic or GI Toxicity)
时间窗: Up to 30 days post radiation, about one month
Acute grade \>= 3 neutropenia or clinically significant \>=2 diarrhea or any grade \>=3 GI toxicity
次要结局
- Progression-free Survival(Up to 36 Months post treatment, a total of about 38 months)
- Acute Adverse Events(Up to 30 days post-treatment, about one month)
研究者
Loren Mell, MD
Associate Professor, Director Division of Clinical and Translational Research, Department of Radiation Medicine and Applied Sciences.
University of California, San Diego