PROTECT: On-line Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Dmean to the pelvic bones
研究概览
简要总结
This prospective, multicenter, nonrandomized phase-II-trial investigates in clinical practice the differences between intensity modulated proton therapy (IMPT) and standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) in the effects on dose-volume parameters and treatment-related morbidity for women with locally advanced cervical cancer undergoing chemoradiation.
详细描述
External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a highly effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient's quality of life (QoL) and may affect ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). However, clinical studies evaluating whether IMPT consequently reduces side effects for LACC are lacking. The PROTECT trial is a nonrandomized prospective multicenter phase-II-trial comparing clinical outcomes after IMPT or IMRT/VMAT in LACC. Thirty women aged >18 years with a histological diagnosis of LACC will be included in either the IMPT or IMRT/VMAT group. Treatment includes EBRT (45 Gy in 25 fractions of 1.8 Gy), concurrent five weekly cisplatin (40 mg/m2), and 3D image (MRI)-guided adaptive brachytherapy. The primary endpoint is pelvic bones Dmean and mean bowel V15Gy. Secondary endpoints include dosimetric parameters, oncological outcomes, health-related QoL, immune response, safety, and tolerability. This study provides the first data on the potential of IMPT to reduce OAR dose in clinical practice and improve toxicity and QoL for patients with LACC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histologically confirmed diagnosis of cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, HPV positive or negative) with an indication for curative treatment with primary chemoradiation with concurrent cisplatin followed by 3D image-guided adaptive brachytherapy.
- •Indication to include the common iliac region (minimum 5, maximum 8) or the common iliac and para-aortic regions (minimum 7, maximum 10) into the elective clinical target volume of the external beam radiotherapy.
- •No distant metastasis beyond the para-aortic lymph node chain as determined by diagnostic imaging (CT or PET-CT scan)
- •Age ≥ 18 years
- •Adequate systemic organ function:
- •Creatinine clearance (> 50 cc/min)
- •Adequate bone marrow function : white blood cells (WBCs) ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
- •Patients must be accessible for treatment and follow-up
- •Written informed consent according to the local Ethics Committee requirements
排除标准
- •Small cell cancer, melanoma and other rare histological types of the cervix.
- •History of another primary malignancy that could conceivably be active evaluated by the study physician. Examples of exception include, but are not limited to:
- •Malignancy treated with curative intent and with no known active disease ≥5 years.
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- •Other severe diseases such as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
- •Previous pelvic or abdominal radiotherapy
- •History of active primary immunodeficiency
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn's disease])
- •The use of immunosuppressive drugs at baseline
- •Contraindications for weekly Cisplatin (or Carboplatin)
- •Contraindications for the use of MRI
研究组 & 干预措施
IMRT/VMAT group
This group receives standard of care curative treatment with primary external beam radiation therapy (IMRT/VMAT), combined with chemotherapy, followed by 3D image (MRI)-guided adaptive brachytherapy.
干预措施: Cisplatin (Drug)
IMRT/VMAT group
This group receives standard of care curative treatment with primary external beam radiation therapy (IMRT/VMAT), combined with chemotherapy, followed by 3D image (MRI)-guided adaptive brachytherapy.
干预措施: Brachytherapy (Radiation)
IMPT group
This group receives curative treatment with primary external beam radiation therapy (IMPT), combined with chemotherapy, followed by 3D image (MRI)-guided adaptive brachytherapy.
干预措施: Cisplatin (Drug)
IMPT group
This group receives curative treatment with primary external beam radiation therapy (IMPT), combined with chemotherapy, followed by 3D image (MRI)-guided adaptive brachytherapy.
干预措施: Brachytherapy (Radiation)
结局指标
主要结局
Dmean to the pelvic bones
时间窗: During treatment
Mean dose to the pelvic bones (Gy).
Mean V15Gy to the bowel
时间窗: During treatment
Mean volume of the bowel (cc) receiving 15Gy.
次要结局
- Distant recurrence-free survival(At Month 12 after end of treatment)
- Health-related Quality of Life(At baseline, week 4 of EBRT, end of treatment, and at Month 3, Month 6, Month 9, and Month 12 after end of treatment)
- Safety and tolerability (toxicity)(At baseline, week 4 of EBRT, end of treatment, and at Month 3, Month 6, Month 9, and Month 12 after end of treatment)
- The effect on the local immune system (analyzed with the Nanostring PanCancer IO 360 panel)(At baseline and at the first brachytherapy session)
- The effect on the systemic immune system(At baseline, week 4 of treatment, and at Month 1, Month 2, Month 3, and Month 12 after end of treatment)
- The effect on bone marrow fat fraction(At baseline, for brachytherapy purposes, and at Month 3 and Month 12 after end of treatment.)
- Key dosimetric parameters of the body(During treatment)
- Key dosimetric parameters of the pelvic bones(During treatment)
- Key dosimetric parameter of the kidneys(During treatment)
- Key dosimetric parameters of the bladder(During treatment)
- Key dosimetric parameters of the rectum(During treatment)
- Key dosimetric parameters of the spinal cord(During treatment)
- Other dosimetric parameters of critical organs(During treatment)
- Key dosimetric parameters of the sigmoid(During treatment)
- Key dosimetric parameters of the bowel(During treatment)
- Overall survival(At Month 12 after end of treatment)
- Pelvic recurrence-free survival(At Month 12 after end of treatment)
- Complete response(At Month 3 after end of treatment)
研究者
Carien Creutzberg
prof., dr.
Leiden University Medical Center