Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-based Therapy.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 101
- 试验地点
- 16
- 主要终点
- Efficacy
研究概览
简要总结
In this clinical trial, the investigators want to know if cabazitaxel is more effective than methotrexate for patients with recurrent or metastatic squamous cell carcinoma of the head and neck in palliative treatment.
详细描述
The principal aim is to evaluate the efficacy of cabazitaxel in patients with palliative head and neck previously treated with platinum-based therapy.
The study design is a non comparative randomized phase II trial: ARM 1: cabazitaxel (20 mg/m2, every 3 weeks) versus ARM 2 methotrexate (40 mg/m2, weekly). Cabazitaxel dose will be increased to 25mg/m2 for the second and subsequent cycles, in the absence of non-hematological AE > grade 2 and hematological AE > grade 3 during the first cycle. (maximum 10 cycles). The aim of the randomization is to offer a valid internal control group by avoiding possible selection bias. However, results obtained in the two treatment group will not be formally compared as this is not the objective of a phase II study.
Tumor check-up will be performed every 9 weeks. Treatment will be continued until disease progression or unacceptable toxicities according to the patient or the investigator. A maximum of 10 cycles of cabazitaxel will be given.
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
- 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
- •Recurrent and/or metastatic head and neck squamous cell carcinoma not amenable to curative treatment with surgery and/or chemotherapy and/or radiation.
- •At least one measurable lesion by MRI or CT-scan according to RECIST 1.
- •Progressive disease within 1 year after first line platinum-based chemotherapy given either as a part of the multimodal curative treatment or in the palliative setting.
- •ECOG performance status 0 -2, in stable medical condition
- •Patients must have an expected survival of at least 3 months
- •Paraffin-embedded tumor tissue available for immunohistochemistry but not mandatory
- •Patients must be over 18 years old and must be able to give written informed consent.
- •Women of child-bearing age or sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine within the 7 days prior to enrollment).
- •Patients must have adequate organ function (Hemoglobin ≥ 9 g/100 ml, Neutrophils ≥ 1,500/mm3, Platelets ≥ 100,000/mm3, total bilirubin <1 time the upper limit of normal (ULN) for age, serum alanine aminotransferase (ALT) < 1.5 1.5 x ULN for age, aspartate aminotransferase (AST) < 1.5 ´ ULN for age , serum creatinine <1.5 x ULN for age.
- •Signed informed consent prior to beginning protocol specific procedure.
- •Sexually active patients must use effective contraception during the period of therapy and up to 150 days after the last treatment dose. Acceptable contraception includes, but is not limited to: oral hormone therapy, partner vasectomy, or double barrier contraception (which is defined as a male condom plus spermicide in combination with either a female condom, or diaphragm, or cervical cap or intrauterine device)
排除标准
- •Non-squamous head and neck cancer
- •Nasopharynx cancer
- •More than two lines of chemotherapy for palliative treatment
- •Surgery or investigational drugs or chemotherapy within 4 weeks before study inclusion. Curative radiation therapy (60-70 Gy) within 8 weeks. For palliative radiation therapy (i.e 8 Gy on a painful lesion) no delay is needed.
- •Previous treatment with cabazitaxel
- •Significant active cardiac disease including: uncontrolled high blood pressure according to the CTCAE 4 grading, unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias
- •Other uncontrolled illnesses (active infections requiring antibiotics, bleeding disorders, uncontrolled diabetes ...)
- •Previous malignancy from which the patient has been disease-free for < 5years, as other than SCCHN.
- •Previous treatments with taxanes and/or anti-EGFR therapy are not an exclusion criteria.
- •Active grade > 2 peripheral neuropathy
- •Active grade > 2 stomatitis
- •Known brain or leptomeningeal involvement
- •History of severe hypersensitivity reaction (> grade 3) to polysorbate 80 containing drugs
- •Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A/
- •A one-week washout period is necessary for patients who are already on these treatments.
- •Organic brain syndrome or significant psychiatric abnormality that would preclude participation in the full protocol and follow up.
研究组 & 干预措施
Methotrexate
Methotrexate is the historical control and has been widely used in SCCHN for palliation.
This medication is an antimetabolite and antifolate drug. It acts by inhibiting the metabolism of folic acid.
干预措施: Methotrexate (Drug)
Cabazitaxel
Cabazitaxel (XRP6258) is a new taxoid, which promotes tubulin assembly in vitro and stabilizes microtubules against cold-induced depolymerization as efficiently as docetaxel
干预措施: Cabazitaxel (Drug)
结局指标
主要结局
Efficacy
时间窗: 18 weeks
Determine the efficacy of cabazitaxel in patients with head and neck cancer in terms of progression-free survival rate at 18 weeks.
次要结局
- Safety profile(18 weeks)