Determination of Tumor Response Rate by RECIST and FDG-PET Criteria to Dacarbazine in Metastatic Soft Tissue and Bone Sarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Best Anatomical Tumor Response
研究概览
简要总结
The purpose of this study is to determine the overall best tumor response rate to dacarbazine given until disease progression as assessed by RECIST criteria, CT and clinical exams in patients with metastatic sarcomas.
详细描述
The two reasons why dacarbazine was eliminated from treatment options for patients with metastatic sarcoma included inability to effectively address the drug's major toxicities (emesis and neutropenia) and the prevailing opinion that the drug was less effective than other chemotherapeutic agents.
Specific Aim #1: The primary endpoint of this study is to determine the overall best tumor anatomic response rate (CR- complete response, PR - partial response, SD - stable disease, or PD - progressive disease) to dacarbazine given until disease progression as assessed by RECIST criteria using CT and clinical examination in patients with metastatic sarcoma.
The prevailing opinion that dacarbazine was less effective than other chemotherapeutic agents in this setting was not based on data from controlled randomized clinical trials. Indeed, we are not aware of a single randomized trial that was conducted and reported which compared the anti-tumor activity of single agent dacarbazine to that of other active single agents in this patient population. However, phase two trials clearly established that dacarbazine had anti-tumor activity in the treatment of metastatic sarcoma, and our personal experience at this institution has confirmed that this is true. In addition, randomized trials demonstrated that the addition of dacarbazine to doxorubicin increased tumor response rates over doxorubicin alone.12 The literature supports the conclusion that dacarbazine has anti-tumor activity in the treatment of metastatic sarcoma.
Historically, in most studies, tumor response to dacarbazine was assessed by WHO criteria. However, current assessment of tumor response usually is based on RECIST criteria, which differ from the WHO criteria, as shown:
Studies have not been performed to determine the tumor anatomic response rate of single agent dacarbazine using RECIST criteria. This study will determine the tumor anatomic response rate as assessed by RECIST criteria to dacarbazine in patients with metastatic sarcoma. Modern methods of CT scans will be used to assess tumor response which contrasts with the earlier methods to assess tumor response to dacarbazine used in most of the published reports. These methods included physical examination and conventional X-ray or first generation, lower resolution CT scans. The current methods of radiologic assessment of tumor response are superior to those used over 15 years ago. The latest generation of CT scans more accurately measure and image a tumor mass, which may better assess tumor response to therapy.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven diagnosis of soft tissue or bone sarcoma
- •Metastatic or locally recurrent and unresectable sarcoma which progressed after one or more prior chemotherapy regimens (excluding adjuvant chemotherapy).
- •At least one measurable tumor lesion (by CT scan) At least one FDG avid (SUV ≥ 3) tumor lesion (by PET/CT) which must have been performed at this institution. At least one of these target lesions must be ≥ 1.5 cm in smallest dimension as measured on the baseline CT
- •Age greater than 18 yrs old
- •ECOG Performance Status of 0-2
- •Baseline ANC ≥ 1000/uL, Hgb ≥ 8 Gr/dL, platelets ≥ 100,000/ dL.
- •Baseline serum creatinine </= 2.0 mg/dL
- •Baseline serum total bilirubin </= 2.0, AST or ALT < 3x ULN
- •No active infection
- •Signed Informed Consent by patient or legally authorized representative
排除标准
- •Current pregnancy or breast feeding.
- •A serious uncontrolled medical disorder that in the opinion of the Investigator would impair the ability of the subject to receive protocol therapy.
- •Chemotherapy, radiation therapy, or investigational agents given with the last 21 days.
- •Investigational agents given with the last 30 days
- •Uncontrolled diabetes mellitus. (Subjects with a fasting blood glucose > 200 at time of PET scanning may need to reschedule to another day after consulting with appropriate physicians.)
研究组 & 干预措施
Dacarbazine
Dacarbazine 850 mg/m^2 IV Day 1 of each 21 day cycle.
干预措施: Dacarbazine (Drug)
结局指标
主要结局
Best Anatomical Tumor Response
时间窗: After completion of 3 cycles
* Complete response (CR): disappearance of all target lesions, disappearance of all non-target lesions, normalization of tumor level marker * Partial response (PR): at least 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD, persistence of one or more non-target lesion and/or maintenance of tumor marker level above the upper limits of normal * Stable disease (SD): neither sufficient shrinkage in target lesions to qualify for PR nor sufficient increase to qualify for progressive disease taking as references the smallest sum LD since the treatment started, persistence of one or more non-target lesion and/or maintenance of tumor marker level above the normal limits of normal * Progressive disease (PD): at least 20% increase in the sum of the LD of target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
次要结局
- Rate of Nausea/Emesis (Any Grade)(Completion of 6 cycles of treatment (18 weeks))
- Rate of Neutropenia (Grade 3/4)(Completion of 6 cycles of treatment (18 weeks))
- Overall Tumor Metabolic Response(After completion of 3 cycles)
- Overall Disease Control Rate(12 months)
- Overall Survival(Until completion of follow-up or patient death (estimated to be 1 year))
- Correlate the Time to Progression With Best Anatomic Response(Completion of follow-up (estimated to be 1 year))
- Correlate Time to Progression With Best Metabolic Response(Completion of follow-up (estimated to be 1 year))
- Correlate the Tumor Metabolic Response Rate With the Tumor Anatomic Response Rate(After completion of 3 cycles)
- Time to Progression (TTP)(Until completion of follow-up (estimated to be 1 year))
- Correlate Overall Survival With Best Anatomic Response(Completion of follow-up (estimated to be 1 year))
- Correlate Overall Survival With Best Metabolic Response(Completion of follow-up (estimated to be 1 year))
- Comparison of the SUV at up to 3 Tumor Sites(Baseline and after every three cycles of treatment (up to 1 year))