A Phase I Study of Doxorubicin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Intraoperative Brachytherapy for Unresectable or Refractory Pelvic and Abdominal Rhabdomyosarcoma and Undifferentiated Sarcomas in Children
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Maximum Tolerated Dose (MTD) of Doxorubicin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of heated doxorubicin that can be given to patients during surgery with abdominal tumors. The safety of this drug will also be studied.
详细描述
Surgery and Study Drug Administration:
If participant is found to be eligible to take part in this study, surgery will be performed to try to remove as many tumors from participant's abdomen as possible. The surgery is not being performed specifically for this research study and would be performed as part of participant's standard of care treatment even if participant didn't take part in this study. Participant will be given a separate consent form to sign that explains the details and risks of the abdominal surgery in more detail.
During the surgery, if it is decided that all of the tumors can be removed, the abdomen will be closed with a plastic tube left in place. Then, the abdominal wash will begin. During the wash, a pump that is connected to the plastic tube pushes the heated doxorubicin into the abdomen and then pulls it out to recirculate the doxorubicin. The heated doxorubicin will be recirculated in and out of the abdomen over 90 minutes while the surgeon gently presses on the abdomen to help the doxorubicin reach all areas in the abdomen. The plastic tube that the heated doxorubicin will be pumped through will stay in place after the surgery to drain the extra fluid. These are the same plastic tubes that would be present even if participant did not agree to take part in this study.
There is a chance that the surgeon may decide during the surgery that the abdominal wash will not be performed, for example if the disease has spread to or attached to certain organs. If this occurs, as many of the tumors will be removed as possible, followed by brachytherapy and the implantation of radioactive seeds. To perform brachytherapy, straws loaded with radioactive seeds will be inserted into the abdominal area. The radiation will then take place in the operating room over about 20 minutes. The straws will be removed before ending the surgery. Participant may be able to return for the abdominal wash procedure 4 weeks after the seeds have been implanted.
Pharmacokinetic Testing:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 1-6 years inclusive
- •Histologically proven RMS (with fusion status) or undifferentiated sarcoma of the pelvis or abdomen, group 3 (as defined by the IRS, intergroup rhabdomyosarcoma study group staging system seen in addendum 1)
- •Radiologic workup must demonstrate that the disease is confined to the abdominal cavity and/or is not metabolically active on PET (Positron Emission Tomography scan), outside of the abdominal cavity.
- •Patients must have a minimum expected duration of survival of greater than 6 weeks as determined and documented by the attending surgeon or medical oncologist.
- •Patients must not have any systemic illness which precludes them from being an operative candidate as determined by anesthesia preoperative evaluation. This includes but is not limited to, sepsis, liver failure, renal failure, cardiovascular failure, pulmonary failure.
- •Patients must have fully intact mental status and normal neurologic abilities. Intact mental status is defined by 'the capacity to identify and recall one's identity and place in time and space. Assessment of mental status and documentation of fully intact mental status by pediatric criteria, will be completed using physical and mental exam by the referring doctor or oncologist.
- •Patients must have adequate renal function defined as creatinine clearance or radioisotope GFR (glomerular filtration rate) >/=70mL/min/1.73m^2 or a serum creatinine based on age/gender less than the listed value in the table below: 1 to <2 years 0.6mg/dL for both males and females, 2 to <6 years 0.8mg/dL for both males and females, 6 to <10 years 1.0mg/dL for both males and females
- •Patients will be eligible if the WBC (white blood cell count) is ≥2000/µl or ANC (absolute neutrophil count) is ≥1,500 and platelets are ≥ 100,000/mm3
- •Patients will be eligible if serum total bilirubin and liver enzymes are ≤ 2 times the upper limit of normal
- •Patients must be recovered from any toxicity from all prior chemotherapy, immunotherapy, or radiotherapy and be at least 14 days past the date of their last treatment
排除标准
- •Patients will be ineligible if they have any concomitant cardiopulmonary disease which would place them at unacceptable risk for a major surgical procedure
- •Patients will be ineligible if they have disease outside of the abdominal cavity which is uncontrolled or PET avid.
- •Patients will be ineligible if they have a baseline neurologic toxicity of Grade 3 or greater.
研究组 & 干预措施
Resectable Intra-Abdominal/Pelvic Tumors
Participants receive complete surgical tumor resection with no gross residual disease, followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) using Doxorubicin.
干预措施: Abdominal Surgery (Procedure)
Resectable Intra-Abdominal/Pelvic Tumors
Participants receive complete surgical tumor resection with no gross residual disease, followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) using Doxorubicin.
干预措施: Doxorubicin (Drug)
Unresectable Intra-Abdominal/Pelvic Tumors
Participants receive debulking surgery followed by intra-operative radiation (IORT) in the form of brachytherapy to the gross residual pelvic tumor sites.
Participants have the option of returning for HIPEC 4 weeks (or more) after IORT, if active disease remains.
干预措施: Abdominal Surgery (Procedure)
Unresectable Intra-Abdominal/Pelvic Tumors
Participants receive debulking surgery followed by intra-operative radiation (IORT) in the form of brachytherapy to the gross residual pelvic tumor sites.
Participants have the option of returning for HIPEC 4 weeks (or more) after IORT, if active disease remains.
干预措施: Intra-Operative Radiation (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Doxorubicin and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
时间窗: 1 day
MTD defined as the highest dose in which 1 or fewer patients in 6 treated experience a dose limiting toxicity (DLT). Hematologic DLT defined as Grade IV neutropenia, anemia, or thrombocytopenia per Common Toxicity Criteria. Non-hematologic DLT is any Grade III or IV non-hematologic toxicity excluding Grade III nausea or vomiting, Grade III hepatic toxicity which returns to Grade I within two weeks of the HIPEC, or before hospital discharge, or Grade III fever occurring after the HIPEC per Common Toxicity Criteria.
次要结局
- Progression of Disease(6 months)