A Pilot Phase II Trial of Adjuvant Radiation Therapy "Sandwiched" Between Ifosfamide in Patients With Mixed Mesodermal Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Cycles With Hematologic Toxicities
研究概览
简要总结
The optimal sequence and /or modality for adjuvant therapy in the management of Mixed Mesodermal Tumors (MMT) clearly remains to be established. The rationale for the protocol is to "sandwich" pelvic radiation with chemotherapy to decrease distant metastasis.
The proposed study will sandwich radiation between the two most active chemotherapeutic agents for MMT identified to date (ifosfamide/cisplatin). By doing so, we attempt to decrease both local and distant recurrence, which may translate into an improved progression free interval and possibly even extend survival.
详细描述
Uterine sarcomas account for only 2-4% of uterine malignancies, yet they are responsible for 26% of uterine cancer deaths. Mixed mesodermal tumors (MMT), previously known as carcinosarcoma, are the most common of the uterine sarcomas in the United States. Prognosis for these patients is generally grim due to the propensity for early metastatic disease. Patterns of spread are by both hematogenous and lymphatic dissemination. It has been noted that 66% of patients with disease clinically confined to the uterus have nodal metastasis at the time of diagnosis. The majority of patients will die with both wide spread intra-abdominal and pelvic disease within two years of diagnosis.
Adjuvant pelvic radiation therapy has been advantageous in controlling local recurrence. One study reports 26% local recurrence in patients treated with surgery alone versus 14% recurrence in patients treated with surgery and adjuvant pelvic radiation. Although adjuvant radiation shows a benefit in improving local control, it has not been found to impact survival. This finding is likely attributed to the high incidence of distant metastasis (85%) known to occur with disease recurrence.
Multiple chemotherapeutic agents have been evaluated in the management of advanced, persistent or recurrent uterine MMT. Response to single agent therapy has been less than 35% with the most active agents identified being ifosfamide (response rate = 34.8%) and cisplatin (response rate 17.9%. The use of chemotherapy in the adjuvant setting has been explored as a means of attempting to impact the incidence of distant metastasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 documented mixed mesodermal tumor (MMT) of uterus with no visible residual disease.
- •Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node sampling.
- •Surgical staging should be completed 6 weeks ± 7 days prior to enrollment.
- •Age >= 18 years.
- •Written voluntary informed consent.
排除标准
- •Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values:
- •Total serum bilirubin >1.5mg/dl
- •History of chronic or active hepatitis
- •Serum creatinine >2.0 mg/dl
- •Platelets <100,000/mm3
- •Absolute neutrophil count (ANC) <1500/mm3
- •Hemoglobin <8.0 g/dl (the patient may be transfused prior to study entry)
- •Patient has severe or uncontrolled medical disease (eg. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
- •Patient has been treated with myelosuppressive chemotherapy within three weeks prior to study entry.
- •Patients with any prior chemotherapy or radiotherapy for pelvic malignancy.
- •Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at time of study entry.
- •Patient has a uterine sarcoma other then mixed mesodermal tumor (MMT).
研究组 & 干预措施
Ifosfamide with or without cisplatin
Participants with surgically staged carcinosarcoma (CS) with no gross residual disease were initially administered ifosfamide (1.2 g/m2/day for 5 days) with cisplatin (20 mg/m2/day for 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin with cisplatin (20 mg/m2/day for 5 days) evrey 3 weeks. cisplatin added toxicity without additional efficacy, so mid-study, cisplatin was eliminated.
干预措施: Ifosfamide (Drug)
Ifosfamide with or without cisplatin
Participants with surgically staged carcinosarcoma (CS) with no gross residual disease were initially administered ifosfamide (1.2 g/m2/day for 5 days) with cisplatin (20 mg/m2/day for 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin with cisplatin (20 mg/m2/day for 5 days) evrey 3 weeks. cisplatin added toxicity without additional efficacy, so mid-study, cisplatin was eliminated.
干预措施: Radiation Therapy (Device)
Ifosfamide with or without cisplatin
Participants with surgically staged carcinosarcoma (CS) with no gross residual disease were initially administered ifosfamide (1.2 g/m2/day for 5 days) with cisplatin (20 mg/m2/day for 5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin with cisplatin (20 mg/m2/day for 5 days) evrey 3 weeks. cisplatin added toxicity without additional efficacy, so mid-study, cisplatin was eliminated.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Cycles With Hematologic Toxicities
时间窗: 2 years
Out of 162 planned cycles, a total of 138 cycles (85%) were administered. Number of cycles during which participants with grades 3 and 4 experienced hematologic toxicities are reported. Most of the toxicities were self-limiting.
次要结局
未报告次要终点
研究者
Mark H. Einstein
Director, Clinical Research for Women's Health
Montefiore Medical Center