A Phase II, Open Label, Non-randomized Study of Second or Third Line Treatment With the Combination of Sorafenib and Everolimus in Patients Affected by Relapsed and Non-resectable High-grade Osteosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Progression Free Survival rate at 6 months
研究概览
简要总结
This is a trial for patients affected by metastatic or relapsed osteosarcoma which progressed after first or further line treatments. In this trial, all patients will be treated until progression or unacceptable toxicity with sorafenib and everolimus. The treatment with sorafenib and everolimus aimed to obtain a 50% rate of patients free from further progression of the disease after 6 months from study entry.
详细描述
Patients affected by metastatic or relapsed osteosarcoma which progressed after first or further line treatments still have a poor outcome. Standard chemotherapy has limited activity in these patients.
In a previous study in patient affected by relapsed unresectable osteosarcoma, sorafenib alone demonstrated promising activity. In the preclinical setting, everolimus was able to improve the activity of sorafenib. Sorafenib and everolimus, by hitting crucial pathways which are essential for osteosarcoma cell proliferation and survival, with an entirely different approach aimed to overcome the resistance to standard chemotherapy showed by relapsed osteosarcoma. In this trial, all patients will be treated with sorafenib and everolimus at the dosage of 800 mg and 5 mg per day, respectively. Both drugs have to be taken orally. The treatment will be continued until progression or unacceptable toxicities. The objective of the present trial is to obtain a 50% rate of patients alive and free from progression of their disease 6 months after trial enrolment. The disease will be evaluated every 2 months with a CT scan.
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
- •Patients with histologically documented and not surgically resectable or metastatic high-grade osteosarcoma which progressed after first or second line treatments for relapsing disease
- •Measurable disease as defined by RECIST criteria vs. 1.1 (bone lesions are allowed). Baseline evaluations must be completed within 28 days prior to enrollment
- •Eastern Cooperative Oncology Group(ECOG) Performance Status of 0 or
- •ECOG PS 2 patients are eligible if the PS 2 depends solely on orthopedic problems
- •Estimated life expectancy of at least 3months
- •Age≥18 years
- •Adequate bone marrow, liver and renal function: Hemoglobin>9.0g/dl, Absolute neutrophil count>1,500/mm3, Platelet>100,000/μl Total bilirubin<1.5 times the upper limit of normal (ULN), ALT and AST<2.5xULN (<5xULN for patients with liver involvement of their cancer), PT-INR/PTT<1.5xULN, Serum creatinine<2xULN
- •Written informed consent
排除标准
- •Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
- •Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function.
- •History of HIV infection and active clinically serious infections (>grade 2 according to NCI-CTCAE vs. 4.0)
- •Symptomatic metastatic brain or meningeal tumors (unless the patient is >6months from definitive therapy, has a negative imaging study within 4weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
- •Patients with seizure disorders requiring medication
- •Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7days of the start of treatment. Both men and women must use adequate barrier birth control measures during the course of the trial and 8weeks after last dose of study drug
- •Patients with evidence or history of bleeding diathesis
- •Patients undergoing renal dialysis
- •Patients unable to swallow oral medications
- •Uncontrolled diabetes (fasting glucose>2xULN)
- •Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤20mg for adrenal insufficiency). Patients receiving corticosteroids must be on a stable dose for ≥4weeks prior to the first dose of Everolimus. Topical or inhaled corticosteroids are permitted
- •Patients with a history of another malignancy within 5years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer skin or other solid tumors curatively treated with no evidence of disease for ≥3years. Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
- •Anticancer chemotherapy or immunotherapy during the study or within 4weeks of study entry
- •Radiotherapy during study or within 3weeks of start of study drug. (Palliative radiotherapy will be allowed)
- •Major surgery within 4weeks of start of study
- •Investigational drug therapy outside of this trial during or within 4weeks of study entry
- •Prior exposure to the study drugs or their analogues
- •Patients with known hypersensitivity to sorafenib, everolimus or other rapamycin analogs, or to its excipients
- •Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- •A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits
研究组 & 干预措施
sorafenib and everolimus
This is an open label study: all patients will be treated with sorafenib 400 mg twice a day in combination with everolimus 5mg per day
干预措施: Sorafenib (Drug)
sorafenib and everolimus
This is an open label study: all patients will be treated with sorafenib 400 mg twice a day in combination with everolimus 5mg per day
干预措施: Everolimus (Drug)
结局指标
主要结局
Progression Free Survival rate at 6 months
时间窗: 6 months from registration into the study
Progression Free Survival rate at 6 months refers to the rate of patients alive and free from progression of the disease at 6 months from registration into the study. Disease will be assessed every 8 weeks up to 2 years until progression or death whichever came first.
次要结局
- progression free survival(From randomization until progression or death whichever came first up to 2 years)
- overall survival(From randomization until death followed up to 5 years)
- Overall response rate(From randomization until progression or death whichever came first up to 2 years)
- Duration of response(calculated from date of first assessement of non-progression until progression or death whichever came first up to 2 years)
- Non-dimensional pattern of response(calculated from randomization until progression or death whichever came first up to 2 years)
- clinical benefit(evaluated at each visit from randomizzation until progression or death whichever came first up to 2 years)
- Safety(assessed at each visit from randomizzation until 28 days after the last dose of study treatment assumption up to 2 years)