An Open-Label Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of Aldoxorubicin in Subjects With Unresectable Glioblastoma Whose Tumors Have Progressed Following Prior Treatment With Surgery, Radiation and Temozolomide
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 4
- 主要终点
- Objective Response Rate (Complete Response and Partial Response)
研究概览
简要总结
This is a pilot study to determine the efficacy and safety of aldoxorubicin in subjects with glioblastoma who have progressed following surgery and prior treatments.
详细描述
This is a second line open-labeled pilot phase 2 study in subjects with glioblastoma whose tumors have progressed following prior treatment with surgery, radiation and Temozolomide. Patients who have received avastin as a second-line treatment are not eligible for this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Age 18 years or older; male or female
- •Histologically or cytologically confirmed unresectable GBM. Subjects with recurrent disease whose prior pathology demonstrated GBM will not need to be re-biopsied. Subjects with prior low-grade glioma or anaplastic glioma are eligible if histological assessment demonstrates transformation into GBM.
- •Cancer progression after treatment with the following: surgery, radiation therapy and temozolomide as first line treatment with no other therapy prior to tumor recurrence.
- •Radiographic progression by RANO Working Group Criteria will be confirmed by Imaging Endpoints, a central imaging vendor.
- •By tumor biopsy if conducted within 4 weeks of randomization.
- •An interval of at least 12 weeks after last dose of radiation and temozolomide is required, unless cancer progression is proven by diagnostic tumor biopsy. If temozolomide is being used in a maintenance phase, there must be a 28-day washout period prior to Randomization.
- •Stable or decreasing dose of corticosteroids for at least 7 days prior to randomization.
- •Capable of providing informed consent and complying with trial procedures.
- •Karnofsky Performance Status 70 or above.
- •ECOG performance status 0-
- •Life expectancy 8 or more weeks.
- •Measurable tumor lesions according to RANO working Group Criteria.
- •a. In the case that there is "non-measurable" disease due to a radical surgical resection during screening, the subject still qualifies if Inclusion #3(b) is met.
- •Women must not be able to become pregnant for the duration of the study.
- •Women of childbearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
- •Geographically accessible to site, i.e. the ability to come to the study site for each scheduled appointment and evaluation.
排除标准
- •Prior exposure to the an anthracycline.
- •Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, radiation and temozolomide.
- •Prior treatment with bevacizumab or an experimental anti-angiogenic agent.
- •Palliative surgery and/or radiation treatment less than 4 weeks to randomization.
- •Exposure to any investigational agent within 30 days of Randomization.
- •History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for 3 or more years.
- •Laboratory values: screening serum creatinine > 1.5xULN, ALT > 2.5xULN, total bilirubin > 1.5xULN, ANC < 1500/mm3, platelet concentrations < 100,000/mm3, absolute lymphocyte count < 1000/mm3, hematocrit level < 27% for females or < 30% for males, serum albumin ≤ 2.5 g/dL, PT/INR 1.5xULN or >3xULN on anticoagulant with no evidence of active bleeding.
- •Evidence of CNS hemorrhage CTCAE ≥ grade 2 on baseline MRI.
- •Clinically evident congestive heart failure > class II of the NYHA guidelines.
- •Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrythmias classified as Lown III, IV or V.
- •History or signs of active coronary artery disease with or without angina pectoris.
- •Serious myocardial dysfunction defined as ultrasound-determined LVEF < 45% of predicted institutional normal value.
- •Baseline ATc>470 msec and/or previous history of QT prolongation.
- •Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or anti-fungals.
- •History of HIV infection.
- •Major surgery, except diagnostic tumor biopsy, within 4 weeks of randomization.
- •Any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
- •Any condition that is unstable and could jeopardize the subject's participation in the study.
研究组 & 干预措施
250 mg/m2 aldoxorubicin
Subjects received 250 mg/m2 aldoxorubicin IV.
干预措施: 250 mg/m2 aldoxorubicin (Drug)
350 mg/m2 aldoxorubicin
Subjects received 350 mg/m2 aldoxorubicin IV.
干预措施: 350 mg/m2 aldoxorubicin (Drug)
结局指标
主要结局
Objective Response Rate (Complete Response and Partial Response)
时间窗: up to 6 months
ORR was defined as the proportion of patients with objective CR or PR by RANO working group criteria. CR: required all the following: complete disappearance of all enhancing measurable/ non-measurable disease sustained for at least 4 weeks; no new lesions; stable or improved non-enhancing (T2/FLAIR) lesions; patients must be off corticosteroids (or on physiologic replacement doses only); and stable or improved clinically. Patients with non-measurable disease only cannot have a CR. PR: Requires all of the following: ≥50% decrease compared with baseline sustained for at least 4 weeks; no PD of non-measurable disease; no new lesions; stable or improved non-enhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at the time of the baseline scan; and stable or improved clinically. Patients with non-measurable disease only can't have a PR.
次要结局
未报告次要终点