Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 149
- 试验地点
- 3
- 主要终点
- Median Progression-Free Survival (PFS)
研究概览
简要总结
In this research study the investigators are looking to see if the combination of docetaxel plus Vandetanib is effective in the treatment of metastatic transitional cell carcinoma (TCC). Docetaxel is a chemotherapy drug that kills cancer cells that are dividing. It is widely used in TCC. Vandetanib is a drug that is believed to stop new blood vessels from forming around cancer cells. The combination of docetaxel and Vandetanib has been studied in people with lung cancer and found to be helpful in killing cancer cells. Thus, this study is looking at people with TCC, to see if the combination of docetaxel plus Vandetanib is better or worse then docetaxel alone.
详细描述
- Because no one knows which of the study options is best, and all of the options are considered equally likely to work, participants will be randomized into one of two study groups: docetaxel plus Vandetanib or docetaxel plus placebo.
- Each treatment cycle lasts three weeks during which time the participant will be taking Vandetanib or placebo once a day, every day. On Day 1 of each cycle (a cycle is 21 days), participants will receive docetaxel as an infusion through a vein in the arm over one hour.
- On Day 1 of every cycle the following tests and procedures will be performed: physical exam and blood tests. On day 1 and on Day 8 of the first cycle only, participants will have an ECG. Every 6-9 weeks (every 2 to 3 cycles), the participants tumor will be assessed by x-ray, CT scan, bone scan, and/or MRI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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 or cytologically confirmed TCC. Mixed histologies are allowed as long as the predominant histology is TCC.
- •Must have received chemotherapy treatment for TCC and have stage IV TCC at the time of study entry. 1-3 prior systemic chemotherapeutic or investigational treatment regimens for TCC are allowed. Patient with more regimens than the ones allowed may be included at the discretion of the Overall Principal Investigator if it is felt that the regimen has shown minimal activity and toxicity and will not influence prior or subsequent therapies. Specifically, participants must meet one or more of the following criteria: a) Progression after treatment with a regimen that includes a platinum salt (e.g. carboplatin or cisplatin) for Stage IV disease OR b) Disease recurrence within two years (from the date of last dose of chemotherapy or surgery until day the informed consent is signed) after neoadjuvant or adjuvant treatment with a regimen that includes a platinum salt.
- •Measurable or evaluable disease, as defined by RECIST. If all sites of measurable or evaluable disease have been irradiated, one site must have demonstrated growth after irradiation.
- •Adequate contraceptive method for subjects with reproductive potential (females with reproductive potential must have a negative serum pregnancy test within 7 days of study entry).
- •ECOG PS 0 or 1
- •18 years of age or older
排除标准
- •History of treatment of TCC (in any setting-neoadjuvant, adjuvant or for metastatic disease) with docetaxel. Patients treated with prior paclitaxel (Taxol) are eligible.
- •History of treatment with a VEGF-axis active agent, including antibodies to VEGF, antibodies to VEGF receptors, or VEGF receptor tyrosine kinase inhibitors.
- •Laboratory results as outlined in the protocol
- •Evidence of uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
- •Clinically significant cardiac event such as myocardial infarction; NHYA classification of heart disease >2 within three months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia
- •History of arrhythmia, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation which is symptomatic or requires treatment (CTCAE Grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
- •Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication.
- •Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.
- •Presence of left bundle branch block (LBBB)
- •QTc with Bazett's correction that is unmeasurable, or 480 msec or greater on screening ECG. If a subject has a QTc of 480msec or greater on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the subject to be eligible for the study.
- •Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function.
- •Hypertension not controlled by medical therapy
- •Currently active diarrhea
- •Women who are currently pregnant or breast feeding
- •Receipt of any investigational agent, chemotherapy or radiation therapy within 21 days prior to Study Day 1
- •Any unresolved non-hematologic toxicity greater than CTCAE grade 1 from previous anti-cancer therapy (other than alopecia).
- •Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy.
- •Grade 2 or greater peripheral neuropathy
- •Previous or current malignancies within the last 3 years, with the exception of in situ carcinoma of the cervix, adequately treated carcinoma of the skin, small renal masses, and adequately treated localized prostate cancer. Other cancers that are highly likely to be cured (cure rate of 75% or greater) may be included at the discretion of the Overall Principal Investigator.
- •History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.
研究组 & 干预措施
Placebo and Docetaxel
Placebo orally and docetaxel intravenously
干预措施: Placebo (Drug)
vandetanib & Docetaxel
vandetanib orally and Docetaxel intravenously
干预措施: Docetaxel (Drug)
vandetanib & Docetaxel
vandetanib orally and Docetaxel intravenously
干预措施: vandetanib (Drug)
Placebo and Docetaxel
Placebo orally and docetaxel intravenously
干预措施: Docetaxel (Drug)
结局指标
主要结局
Median Progression-Free Survival (PFS)
时间窗: Disease evaluations occurred at week 6 and 12 and thereafter every 3 cycles/9 weeks on treatment and every 3 months in follow-up. Participants were followed until PD, death or lost to follow-up. Median survival follow-up was 12 months (range 1-26).
PFS based on the Kaplan-Meier method is defined as the time between randomization and documented disease progression (PD) per RECIST 1.0 criteria or death, or is censored at time of last disease assessment. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
次要结局
- Median Overall Survival(Off treatment, patients were followed for survival information every 6 months (±1 month) until death,up to 2 years after discontinuing therapy, or until lost to follow-up. Median survival follow-up for the study cohort was 12 months (95% CI: 9-18 months).)
- Grade 3-5 Toxicity Rate(Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort approximated 2 cycles (range 1-31).)
- Objective Response Rate(Disease evaluations occurred at week 6 and 12 and thereafter every 3 cycles/9 weeks on treatment. Median treatment duration for this study cohort approximated 2 cycles (range 1-31).)
研究者
Toni Choueiri, MD
Assistant Professor of Medicine, Harvard Medical School
Dana-Farber Cancer Institute