Phase I/II Trial of Cabazitaxel in Adult Patients With Recurrent Malignant Glioma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The goal of Part 1 of this clinical research study is to find the highest tolerable dose of cabazitaxel that can be given to patients with glioblastoma. The goal of Part 2 is to learn if cabazitaxel can help to control glioblastoma. The safety of the study drug will also be studied in both parts.
Cabazitaxel is designed to interfere with the growth of cancer cells by stopping cell division.
详细描述
Study Parts/Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 5 groups of 3-6 participants will be enrolled in Part 1 of the study. After that, up to 44 participants will be enrolled in Part 2.
If you are in Part 1, you will be assigned to a dose level of cabazitaxel based on when you join this study. Up to 5 dose levels of cabazitaxel will be tested. Two (2) dose levels will be given over 60 minutes, and 3 will be given over 30 minutes. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose level of cabazitaxel than the group before it, if no intolerable side effects were seen. Your dose may be lowered if you have side effects.
If you are in Part 2, you will receive cabazitaxel at the highest dose that was tolerated in Part 1.
Study Drug Administration:
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
- •Adults (>/=18 years of age)
- •Karnofsky performance score >/=60
- •Histologically proven WHO grade III and IV malignant gliomas for phase I of the study and supratentorial WHO grade IV malignant glioma (GBM and gliosarcoma) for Phase II.
- •Unequivocal evidence for tumor recurrence or progression by MRI scan.
- •For the phase I portion of the study, any number of prior relapses is permitted, provided all other eligibility criteria are met.
- •For the phase II portion of the study, no more than 2 prior relapses are allowed.
- •Must have failed prior chemo-radiation therapy and must be >/=12 weeks from completion of the chemo-radiation therapy, unless tumor progression has been confirmed by either surgery or by appropriate imaging studies (e.g. PET scan, MR spectroscopy, etc.).
- •Baseline on-study MRI within 14 days prior to registration on stable or decreasing dose of steroids. If the steroid dose is increased between the date of imaging and the initiation of therapy (or at that time), a new baseline MRI is required.
- •Must have recovered from the toxic effects of prior therapy: 4 weeks from any investigational agents, 4 weeks from cytotoxic agents, two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, 3 weeks from bevacizumab (phase I only) and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, cis-retinoic acid, cytostatic agents such as signal transduction inhibitors etc given prior to trial entry as a non-investigational agent etc. (radiosensitizer does not count), at least 2 weeks from prior surgery.
- •Acceptable lab values including absolute neutrophil count >/= 1,500/mm3 , Hemoglobin >/= 8.0 g/dl, Platelet count >/= 100,000/mm3, total bilirubin </= upper limit of normal (ULN), AST (SGOT) </= 1.5 x ULN, ALT (SGPT) </= 1.5 x ULN and Creatinine </= 1.5 x ULN.
- •Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 14 days prior to initiation of therapy.
- •Men and women of childbearing potential must be willing to consent to practice abstinence or using effective contraception while on treatment and for at least 1 month thereafter.
- •No prior malignancies for >/= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast.
- •Must provide informed consent prior to protocol specific procedures.
- •Prior bevacizumab allowed in phase I (washout period of 3 weeks necessary from the last dose).
排除标准
- •Any serious medical condition or laboratory abnormality which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. These would include active infection (including persistent fever), diseases or conditions that obscure toxicity or dangerously alter drug metabolism, serious intercurrent medical illness (e.g. symptomatic congestive heart failure).
- •Any serious medical condition or psychiatric illness that would prevent the subject from providing informed consent.
- •Females who are pregnant or breast feeding.
- •Known hypersensitivity to cabazitaxel or to polysorbate 80 (Prior cabazitaxel allowed if used >3 yr for other malignancies and tolerated well).
- •Prior bevacizumab not allowed for phase II.
- •Concurrent use of other anti-cancer agents or treatments.
- •Patients must not be on enzyme inducing anticonvulsants (EIAED) due to its potential influence on cabazitaxel pharmacology; if the treating physician elects to change the medication to a non-enzyme inducing agent, a 1-week wash out period will be required after stopping EIAED prior to initiation of cabazitaxel.
- •Unable or unwilling to follow study requirements and schedule
- •CYP3A inducing or inhibiting drugs are not permitted. Hepatic enzyme inducing antiepileptic drugs are also hence not permitted while on study. A one-week wash out period after discontinuing such drugs is required prior to initiating treatment with Cabazitaxel.
研究组 & 干预措施
Cabazitaxel
Cabazitaxel by vein on day 1 of each 3 week cycle.
Phase I: Up to 5 dose levels of cabazitaxel tested. Two (2) dose levels will be given over 60 minutes, and 3 will be given over 30 minutes. First group of participants receive the lowest dose level. Each new group receives a higher dose level of cabazitaxel than the group before it, if no intolerable side effects were seen.
Phase II: Cabazitaxel at the highest dose that was tolerated in Phase I.
干预措施: Cabazitaxel (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 3 weeks
The MTD of Cabazitaxel defined as the dose level at which no more than 1 out of 6 subjects experiences DLT. Toxicities graded according to the Common Terminology Criteria for Adverse events (CTCAE) Version 4.0. If multiple toxicities are seen, the presence of DLT should be based on the most severe toxicity experienced.
次要结局
- Progression Free Survival (PFS)(6 months)