Docetaxel, Irinotecan, Recurrent, Refractory, Bone and Soft Tissue Sarcomas
试验速览
- 阶段
- 2 期
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- CT or MRI image of tumor
研究概览
简要总结
The purpose of this study is to estimate the control rate (CR,PR,SD) of docetaxel and irinotecan (DI) combination chemotherapy for recurrent or refractory bone and soft tissue sarcomas.Al so, this study is to evaluate the toxicity profile of Docetaxel and Irinotecan (DI) combination chemotherapy.
详细描述
Treatment setting:Hospitalization is preferred, but treatment on the outpatient base is allowed.
Regimen and premedication
- Regimen Docetaxel 100 mg/m2 mixed in D5W or N/S IV over 60 min: Day 1 Irinotecan 80 mg/m2 mixed in D5W IV over 90 min: Days 1 and 8
- Premedications Dexamethasone 3 mg/m2 PO or IV 12 hours and 1 hour prior to docetaxel administration. A third dose of dexamethasone will be given 8 hours following docetaxel infusion. Patients should not be treated with docetaxel if they did not start the PO premedication the previous day. Parenteral pheniramine maleate may be given prior to docetaxel if patient has had a previous hypersensitivity to the agent. If used, pheniramine maleate (1 mg/kg IV) should be administered 30 minutes prior to infusion and every six hours thereafter, as needed.
Treatment interval and overall treatment period : Therapy consists of 3-week cycles comprising weekly treatment for 2 weeks (docetaxel on D1 and irinotecan on D1 and D8) followed by 1-week rest, and will be continued in the absence of disease progression or unacceptable toxicity. Maximal number of cycles is twelve, however, additional cycles may be employed only when at least PR is maintained and patients want to take more.
Treatment modifications : Toxicity is evaluated according to common terminology criteria for adverse events v3.0 (CTCAE) of the National Cancer Institute.
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
- 5 Years 至 49 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic diagnosis of rhabdomyosarcoma, liposarcoma, leiomyosarcoma, malignant fibrous histiocytoma, angiosarcoma, fibrosarcoma, malignant hemangiopericytoma, desmoplastic small round cell tumor, epitheloid sarcoma, clear cell sarcoma, synovial sarcoma, extraskeletal chondrosarcoma, alveolar soft part sarcoma, sarcoma not otherwise specified, malignant peripheral nerve sheath tumor, osteogenic sarcoma, Ewing's sarcoma/PPNET
- •One or more prior chemotherapy: Refractory tumors are defined as non-responsiveness to one or two regimens. In children less than 18 years, ifosfamide/carboplatin/etoposide (ICE) or VICE (vincristine + ICE) chemotherapy is recommended as a prior salvage regimen but is not mandatory.
- •Non-resectable recurrent or refractory rhabdomyosarcoma, liposarcoma, leiomyosarcoma, malignant fibrous histiocytoma, angiosarcoma, fibrosarcoma, malignant hemangiopericytoma, desmoplastic small round cell tumor, epitheloid sarcoma, clear cell sarcoma, synovial sarcoma, extraskeletal chondrosarcoma, alveolar soft part sarcoma, sarcoma not otherwise specified, malignant peripheral nerve sheath tumor, osteogenic sarcoma, Ewing's sarcoma/PPNET
- •Debulking surgery for non-resectable tumors is allowed when remained mass post-debulking is measurable enough to evaluate the response to DI.
- •Disease status must be that of measurable disease defined as:
- •Lesions that can be accurately measured in at least one dimension with longest diameter >20mm using conventional techniques or >10mm with spiral CT scan.
- •Age less than 50 years
- •Predicted life expectancy of more than 8 weeks
- •Performance status: ECOG 0-2 or Karnofsky ≥ 50% for patients more than 10 years of age, and Lansky ≥ 50% for children equal or less than 10 years of age.
- •Adequate major organ function defined as; Hematopoietic function: ANC> 750/μL, platelet count>75,000/μL (If peripheral blood counts are inadequate due to bone marrow infiltration, then following a bone marrow biopsy to document disease, the patient will be eligible for study, but will be inevaluable for hematological toxicity. Patients with no increase in the infiltration of the marrow on follow-up marrow exams may receive further therapy with inadequate blood counts if they have recovered from all non-hematologic toxicities.) Hepatic function: bilirubin <1.5 mg/dL, AST/ALT levels <2.5 X UNL Renal function: creatinine <1.5 X UNL for age (Table 3) or GFR ≥ 50 ml/min/1.73m2
- •Patients must not receive any other anti-cancer agents or other investigational agents during the course of this investigation or within 3 weeks prior to study entry. At least 8 weeks must have elapsed since administration of extended radiotherapy or nitrosurea. Evaluable lesions must not have any radiotherapy within 8 weeks of the start of this protocol. Previously irradiated lesions that are used to evaluate tumor response must have shown evidence of an interim increase in size. For patients who have had stem cell transplant, they must have evidence of stable engraftment without the need for significant blood product support or cytokine therapy.
- •Patients and/or their parents or legal guardians should sign a written informed consent.
排除标准
- •Patients who have received either prior docetaxel or irinotecan.
- •Patients who are taking anticonvulsants.
- •Patients with uncontrolled infections.
- •Women of childbearing age must not be pregnant or lactating.
- •Inadequate cardiovascular function
- •Other malignancy within the past 3 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
- •Psychiatric disorder that would preclude compliance
研究组 & 干预措施
Docetaxel and Irinotecan (DI)
Combination chemotherapy of Docetaxel and Irinotecan (DI) in recurrent or refractory bone and soft tissue sarcomas.
Docetaxel and Irinotecan (DI) have different biologic targets, mode of action and mechanism of resistance. Preclinical studies have demonstrated an additive or synergistic effect of irinotecan and taxanes when used in combination in human.
Docetaxel 100 mg/m2 mixed in D5W or N/S IV over 60 min: Day 1 Irinotecan 80 mg/m2 mixed in D5W IV over 90 min: Days 1 and 8 Therapy consists of 3-week cycles comprising weekly treatment for 2 weeks (docetaxel on D1 and irinotecan on D1 and D8) followed by 1-week rest, and will be continued in the absence of disease progression or unacceptable toxicity.
干预措施: Docetaxel (Taxotere) (Drug)
Docetaxel and Irinotecan (DI)
Combination chemotherapy of Docetaxel and Irinotecan (DI) in recurrent or refractory bone and soft tissue sarcomas.
Docetaxel and Irinotecan (DI) have different biologic targets, mode of action and mechanism of resistance. Preclinical studies have demonstrated an additive or synergistic effect of irinotecan and taxanes when used in combination in human.
Docetaxel 100 mg/m2 mixed in D5W or N/S IV over 60 min: Day 1 Irinotecan 80 mg/m2 mixed in D5W IV over 90 min: Days 1 and 8 Therapy consists of 3-week cycles comprising weekly treatment for 2 weeks (docetaxel on D1 and irinotecan on D1 and D8) followed by 1-week rest, and will be continued in the absence of disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
结局指标
主要结局
CT or MRI image of tumor
时间窗: 2 cycles after chemotherapy (6 weeks, 1cycle = 3 weeks)
次要结局
未报告次要终点
研究者
Byung-Kiu Park
Head of Center for Pediatric Oncology
National Cancer Center, Korea