NCT00117637已完成2 期
A Randomised, Open-label, Multi-centre Phase II Study of BAY43-9006 (Sorafenib) Versus Standard Treatment With Interferon Alpha-2a in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 189
- 主要终点
- Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period
研究概览
简要总结
The purpose of the study is to:
- Find out if patients receiving BAY43-9006 will live longer without tumor progression than those receiving standard therapy with interferon alpha-2a
- Find out if a higher dose of BAY43-9006 can inhibit tumor progression in patients who progressed during standard dose treatment with BAY43-9006, and for how long these patients live without progression
- Find out how long patients live without progression who receive BAY43-9006 after failing to respond to standard therapy with interferon alpha-2a
- Find out in how many percent of patients BAY43-9006 prevents the growth of or shrinks kidney tumors and/or their metastases depending on treatment and dosage
- Find out if BAY43-9006 has any effect on the quality of life of patients with kidney cancer
- Find out the level of BAY43-9006 in the blood once per month and any changes in this level
- Find out whether BAY43-9006 effects are associated with specific biomarkers
详细描述
Analyses on Biomarkers were exploratory and assessed as tertiary objective of the trial.
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
- •Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
- •Male or female patients >= 18 years of age
- •Patients who have a life expectancy of at least 12 weeks
- •Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (Renal Cell Carcinoma) histologically or cytologically documented
- •Patients must have undergone prior (at the time of primary diagnosis) complete surgical excision of primary RCC tumor
- •Patients must have had no prior systemic therapy for advanced RCC. Prior systemic therapy is defined as any treatment with a chemotherapy agent (or regimen), an immunotherapy agent (or regimen) or an investigational treatment agent (or regimen) against the renal cell carcinoma. Megestrol acetate or medroxyprogesterone will constitute as a prior systemic therapy
- •Patients who have at least one uni-dimensional measurable lesion by CT (Computed tomography)-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST)
- •Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate bone marrow, liver , and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening
- •Hemoglobin >9.0 g/l
- •Absolute neutrophil count ( ANC)>1,500/mm3
- •Platelets> or = 100,000/ul
- •Total bilirubin < 1.5 x the upper limit of normal
- •ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
- •Amylase and lipase < 1.5 x the upper limit of normal
- •Serum creatinine < 2.0 x the upper limit of normal
- •PT (Prothrombin Time) or INR (International Normalized Ratio) and PTT (Partial Thromboplastin Time) < 1.5 x upper limit of normal (patients who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate. For patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care)
排除标准
- •Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta [Noninvasive papillary carcinoma], Tis [Carcinoma in situ: "flat tumor"]&T1 [Tumor invades subepithelial connective tissue]) or any cancer curatively treated > 5 years prior to study entry
- •Complete renal shut-down requiring hemo- or peritoneal dialysis
- •History of cardiac disease : congestive heart failure > NYHA (New York Heart Association) class 2: active cardiovascular disease( MI (Distant metastasis) more than 6 months prior to study entry is allowed); cardiac arrhythmia requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
- •Active clinically serious bacterial or fungal infections (>= grade 2 NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), Version 3)
- •Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
- •Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to this brain tumour site at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies (head CT or MRI at screening always required)
- •Patients with seizure disorder requiring medication (such as steroid anti-epileptics)
- •History of organ allograft
- •Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- •Known or suspected allergy to the investigational agent or any agent given in association with this trial
- •Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
- •Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial
研究组 & 干预措施
First Sorafenib (Nexavar, BAY43-9006) 400 mg then 600 mg
Experimental
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
干预措施: Sorafenib (Nexavar, BAY43-9006) (Drug)
First Interferon then Sorafenib (Nexavar, BAY43-9006) 400 mg
Active Comparator
Interferon (IFN) α-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period.After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
干预措施: Interferon (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period
时间窗: From randomization of the first subject until 15 months later, assessed every 8 weeks
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
次要结局
- Disease Control (DC) According to Independent Central Review for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Overall Survival (OS)(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Average of All Trough Plasma Concentrations(From start of treatment of the first subject until 15 months later assessed every 4 weeks.)
- Duration of Response According to the Independent Radiological Review for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Disease Control (DC) According to the Investigator Assessment for the First Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Tumor Response According to the Independent Radiological Review for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Tumor Response According to the Investigator Assessment for the First Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Time to Response According to the Investigator Assessment for the First Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks)
- Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Tumor Response According to the Investigator Assessment for the Second Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Progression Free Survival According to the Investigator Assessment (Second Intervention Period)(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks)
- Slope - Change in Trough Concentration/Cycle(From start of treatment of the first subject until 15 months later assessed every 4 weeks.)
- Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks)
- Duration of Response According to the Investigator Assessment for the First Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Duration of Response According to the Investigator Assessment for the Second Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks)
- Time to Response According to the Independent Radiological Review for the First Intervention Period(From randomization of the first subject until 15 months later, assessed every 8 weeks)
- Time to Response According to the Investigator Assessment for the Second Intervention Period(From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks)
研究者
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