A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 131
- 试验地点
- 18
- 主要终点
- Anti-tumor Activity as Measured by Median Progression Free Survival Time
研究概览
简要总结
To compare the anti-tumor activity of everolimus and sunitinib in subjects with metastatic renal cell carcinoma (mRCC) with non-clear cell pathology.
详细描述
This will be an international (USA, Canada, and UK) open-label, outpatient, multicenter, randomized study of treatment with RAD001 (everolimus (Afinitor®) or sunitinib (Sutent®) in subjects with mRCC and non-clear cell histology. Special emphasis is placed on papillary and chromophobe histologies while sarcomatoid clear cell variants, medullary, and collecting duct carcinomas will be excluded (see eligibility). Subjects may continue receiving study drugs until disease progression, unacceptable toxicities, or withdrawal of consent, for a maximum of 24 months. Continuation of study assigned treatment will be allowed beyond 24 months at the discretion of the sponsor. Stratification variables will include histology (papillary vs. chromophobe) and Motzer risk criteria (0, 1-2, and 3). Tumor progression will be assessed locally and by independent review, in strict accordance with Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria measured every 12 weeks. At the time of progression, subjects will be taken off study other than simple administrative mortality follow-up. Primary pathologic samples and plasma/urine angiokine levels at baseline and over time will be collected and stored centrally for biomarker analysis.
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
- •Histologically confirmed advanced Renal Cell Carcinoma (RCC), with non-clear cell pathology.
- •RCC tumor tissue available for correlative sciences, from either primary or metastatic site or both.
- •At the time of screening, at least 4 weeks since prior palliative radiation therapy and/or major surgery, and resolution of all toxic effects of prior therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 4.0) Grade
- •Subject must have radiographic evidence of metastatic disease with at least 1 measurable per RECIST 1.1 criteria (Attachment 1)].
- •Age > 18 years.
- •Adequate laboratory values
- •Karnofsky Performance Status ≥ 60 (Attachment 2).
- •Life expectancy of at least 3 months.
- •Written, signed, dated, and witnessed Institutional Review Board (IRB) or Institutional Ethics Committee (IEC) approved informed consent form (ICF) before any screening procedures are performed.
排除标准
- •Subjects with a history of or active central nervous system (CNS) metastases.
- •Prior systemic therapy for RCC, including mTOR and anti-angiogenic therapy, chemotherapy, biologic or experimental therapy.
- •Subjects with collecting duct, medullary, small cell, oncocytoma, or lymphoma-type pathology.
- •Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.
- •Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the screening visit.
- •Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.
- •Presence of a non-healing wound or ulcer.
- •Grade 3 hemorrhage within the past month.
- •Hypertension with systolic blood pressure of >180 mm Hg and/or diastolic pressure >100 mm Hg.
- •Subjects with American Heart Association (AHA) Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction <50%, or history of unstable angina, myocardial infarction, coronary artery bypass graft, cerebrovascular accident, transient ischemic attack, or pulmonary embolism within 6 months of entry.
- •Diabetes mellitus with glycosylated hemoglobin A1c (HbgA1c) > 10% despite therapy.
- •A history of interstitial pneumonitis.
- •Subjects with active autoimmune disorder(s) being treated with immunosuppressive agents within 4 weeks prior to the screening visit.
- •Subjects receiving immunosuppressive agents and those with chronic viral/bacterial/fungal illnesses such as human immunodeficiency virus (HIV).
- •Patients who have receive immunization with attenuated live vaccines within one week of study entry or during study period.
- •Patients with active infection(s), active antimicrobial therapy or serious intercurrent illness.
- •History of other prior malignancy in past 5 years.
- •Pregnant or nursing women.
- •Major medical/psychiatric illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study, including inability to absorb oral medications and history of noncompliance to medical regimens.
- •Known hypersensitivity to any of the components in everolimus or sunitinib product
- •Subjects taking agents that significantly prolong the QTc interval are not eligible.
- •Proteinuria with a spot urine protein/creatinine ratio >2 or 24 hour urine protein >2 grams per 24 hours.
- •Severely impaired lung function as defined as spirometry and Carbon Monoxide Diffusing Capacity (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air.
- •Advanced liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
研究组 & 干预措施
RAD001
Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.
干预措施: Everolimus (Drug)
Sunitinib
Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
干预措施: Sunitinib (Drug)
结局指标
主要结局
Anti-tumor Activity as Measured by Median Progression Free Survival Time
时间窗: 24 Months
The primary objective will be to compare the anti-tumor activity of everolimus and sunitinib in subjects with mRCC with non-clear cell pathology, as measured by progression-free survival (PFS) following treatment initiation according to RECIST 1.1 criteria. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
次要结局
- Median OS(Up to 40 months)
- Overall Response Rate(24 months)
- Progression Free Survival Rates(6, 12 and 24 months)
- PFS Expressed in Months(24 months)
- Overall Survival Rates(6, 12, 24, 36 months)
- Percentage of Participants With Adverse Events(24 months)
- Change in Quality-of-life(baseline, up to 40 months)
- Percentage of Participants With Stable Disease (SD)(Baseline to 36 months)
- 12 Week Clinical Benefit Rate as Percentage(Baseline to 36 months)
- Best Tumor Shrinkage as a Percentile in Each Arm(24 months)
- Median Duration of Response (CR, PR, and SD)(24 months)
- Time-to-new Metastatic Disease in Each Treatment Arm(36 months)