A Single Arm, Open-label Multicenter Phase II Trial of Everolimus in Patients With Relapsed/Refractory Germ Cell Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 8
- 主要终点
- Progression-free rate at 12 weeks
研究概览
简要总结
The purpose of this study is to determine whether the drug everolimus is effective in the treatment of patients with relapsed cancer of the testis. This is a phase II study where all patients will receive the study drug (everolimus 10 mg daily). The primary endpoint of the study is the rate of patients that have no progressive disease after 12 weeks of treatment. Twenty-five evaluable patients will be treated in this study.
详细描述
Rationale
Patients with metastatic germ cell cancer and relapse after two or more courses of cisplatin-based chemotherapy or after high-dose chemotherapy have a poor prognosis and few treatment options. Everolimus is a derivative of rapamycin and acts as a signal transduction inhibitor. Its target is mTOR (mammalian target of rapamycin), a key protein kinase regulating cell growth, proliferation and survival. The mTOR pathway activity is modulated by the PI3K1AKT pathway and is known to be deregulated in numerous human cancers, including germ cell tumors. Everolimus is being investigated as an anticancer agent based on its potential to act:
- Directly on tumor cells by inhibiting tumor cell growth and proliferation
- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity
Study design
An open-label, single arm, non-randomized, single stage phase II study. Screening phase: Baseline evaluations will be performed within 2 weeks before the first dose of study drug. Treatment phase: All patients will receive everolimus until disease progression (by RECIST or tumor markers) or unacceptable toxicity or study discontinuation for other reasons. A treatment cycle consists of 3 weeks. Dose reductions and dose interruptions (for up to 2 weeks) are allowed for intolerable toxicity. Follow-up phase: All patients will be followed for survival.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients >= 18 years old.
- •Patients with histologically proven seminomatous or non-seminomatous germ cell cancer
- •Disease progression during cisplatin-based chemotherapy or
- •Disease progression or relapse after high-dose chemotherapy or
- •Disease progression or relapse after at least 2 different cisplatin-based regimens and contraindications for high-dose chemotherapy.
- •Patients must have received prior combination chemotherapy with gemcitabine, oxaliplatin and paclitaxel (GOP). Prior treatment with a combination of two of these drugs is allowed in case of contraindications for GOP.
- •Disease progression at study entry: progressive disease according to RECIST criteria in baseline examinations or tumor marker increase > 25% within 4 weeks before study entry.
- •ECOG performance status <=
- •Life expectancy >= 3 months.
- •Adequate bone marrow function: absolute neutrophil count >= 1.5 x 109/1, platelets >= 75 x 109/1, hemoglobin >= 9 g/dl.
- •Adequate liver function: serum bilirubin: <= 1.5x ULN, ALT and AST <= 2.5x ULN. For patients with known liver metastases: AST and ALT <= 5x ULN.
- •Adequate renal function: serum creatinine <= 2.0x ULN.
- •Patients must be surgically sterile or must agree to use effective contraception during study treatment.
- •Signed written informed consent.
排除标准
- •Systemic antitumor treatment within 21 days before study entry.
- •Simultaneous radiotherapy of the only target lesion(s).
- •Patients who have undergone major surgery within 4 weeks prior to starting study drug (e.g. intra-thoracic, intra-abdominal, or intra-pelvic) or significant traumatic injury, or who have not recovered from the side effects of any of the above
- •Patients who have previously received mTOR inhibitors (sirolimus, temsirolimus, everolimus).
- •Patients receiving chronic systemic treatment with corticosteroids (dose of >= 20 mg/day methylprednisone equivalent) or another immunosuppressive agent.
- •Patients with unstable angina pectoris, myocardial infarction <= 6 months prior to first study treatment, congestive heart failure NYHA III-IV or serious uncontrolled cardiac arrhythmias.
- •Patients with severely impaired lung function: spirometry or DLCO < 50% of the normal predicted value.
- •Uncontrolled diabetes: fasting serum glucose > 2.0x ULN.
- •Patients with an active or uncontrolled infection, incl. chronic Hepatitis B or C
- •Patients who have a history of another primary malignancy and are off treatment for <= 3 years, with the exception of non-melanoma skin cancer.
- •Patients who have participated in another clinical trial within 30 days before study entry.
- •Other serious medical conditions that could impair the ability of the patient to participate in the study.
- •Patients unwilling or unable to comply with the protocol.
研究组 & 干预措施
Everolimus 10 mg daily
干预措施: Everolimus (Drug)
结局指标
主要结局
Progression-free rate at 12 weeks
时间窗: 12 weeks
Percentage of patients that have not progressed after 12 weeks of treatment.
次要结局
- Overall survival(12 months)
- Objective response rate(6 months)
- Safety profile(6 months)