NCT02724878已完成2 期
Phase II Study of Atezolizumab + Bevacizumab in Patients With Advanced Non-Clear Cell 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
- 入组人数
- 65
- 试验地点
- 4
- 主要终点
- Best Overall Response Rate
研究概览
简要总结
This research study is studying the combination of Atezolizumab and Bevacizumab as a possible treatment for Advanced Non-Clear Cell Kidney Cancer.
详细描述
This research study is a Phase II clinical trial. In this research the investigators are studying the combination of Atezolizumab with Bevacizumab. Participants will receive both vascular endothelial targeted therapy and immunotherapy.
The FDA (the U.S. Food and Drug Administration) has not approved Atezolizumab for Advanced Non-Clear Cell Kidney Cancer, but it has been approved for other uses.
The FDA has approved Bevacizumab with Interferon (IFNα) as a treatment option for Advanced Kidney Cancer.
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
- •Age ≥ 18 years.
- •Unresectable advanced or metastatic non-clear cell RCC to include but not limited to:
- •Papillary RCC, any type
- •Unclassified RCC
- •Translocation RCC
- •Chromophobe RCC
- •Collecting duct RCC
- •Medulary RCC
- •Clear cell RCC or any histology with > 20% sarcomatoid features will be eligible.
- •Other non-clear cell histologies that are not included above need to be discussed with the PI.
- •Request for formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens if available and willingness of the participant to undergo mandatory fresh tumor biopsy unless determined medically unsafe or not feasible. A note from the study team should be provided documenting availability of tissue. If a target lesion is biopsied at screening, this lesion must be followed as non-target lesion after the biopsy unless it is the patient's only target lesion. If there is only one target lesion, it should be followed as a target lesion regardless.
- •The archival specimen should contain adequate viable tumor tissue.
- •The specimen may consist of a tissue block (preferred and should contain the highest grade of tumor) or at least 30 unstained serial sections. Fine-needle aspiration, brushings, cell pellet from pleural effusion, bone marrow aspirate/biopsy are not acceptable.
- •Fresh tumor biopsy at progression will be required in cases where patients experience relapse after an initial response if medically safe.
- •Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.
- •ECOG performance status ≤ 2 (See Appendix A).
- •Adequate hematologic and end-organ function as defined by the following laboratory results obtained within 28 days prior to the first study treatment:
- •Absolute neutrophil count (ANC) ≥ 1500 cells/uL.
- •Lymphocyte count ≥ 500/uL.
- •Platelet count ≥ 100,000/uL.
- •Hemoglobin ≥ 9 g/dL (patients may be transfused to meet this criterion).
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions: Patients with documented liver metastases should have AST and ALT ≤ 5 x ULN.
- •Serum bilirubin ≤ 2.0 x ULN with the following exception: Patients with known Gilbert's disease should have a serum bilirubin ≤ 3 x ULN.
- •Creatinine clearance ≥ 30 mL/min as calculated by Cockcroft-Gault equation.
- •For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective forms of contraception and to continue its use 6 months after the last dose of atezolizumab or bevacizumab.
- •Signed informed consent form.
- •Ability and capacity to comply with study and follow-up procedures.
- •Exclusion Criteria
- •Prior treatment with CD137 agonists, anti- cytotoxic T-lymphocyte-associated protein 4, anti-PD-1, or anti-PDL1 therapeutic antibody or pathway targeting agents.
- •Prior IFNα or IL-2 is allowed following 4 week washout from treatment end date.
- •Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 4 weeks of enrollment.
- •Prior therapy with bevacizuamab.
- •Thrombologic event within 3 weeks of treatment start date, unless stable on anticoagulation with LMWH or Factor Xa inhibitor for at least 2 weeks.
- •Treatment with systemic immunosuppressive medications including but not limited to: prednisone, dexamethasone, cyclosporin, azathioprine, methotrexate, thalidomide, anti- tumor necrosis factor (TNF) agents, hydroxychloroquine within 2 weeks of first study dose.
- •Patients who have received acute, low-dose systemic immunosuppressant medications may be enrolled.
- •Patients with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled.
- •The use of inhaled, topical intraocular, or intra articular corticosteroids or, mineralocorticoids are allowed.
- •Radiotherapy for RCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to the initiation of study treatment. Stability must be confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) imaging and/or treating investigator determination.
- •Malignancies other than RCC within 2 years of first study treatment with the exception of those with negligible risk of metastases or death (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma, or other malignancy not deemed to impact that patients 5-year life expectancy).
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
- •Known hypersensitivity to any component of the atezolizumab product.
- •History of autoimmune disease including: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on thyroid replacement hormone or those with autoimmune dermatologic conditions not requiring the use of prednisone > 10 mg or equivalent are eligible.
- •History of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in the radiation field is permitted.
- •Positive test for HIV (test to be performed within 28 days of first treatment start).
- •Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening). Patients with past/resolved HBV infection (defined as having negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. A negative HBA DNA test must be obtained in patients with positive hepatitis B core antibody prior to Cycle 1 Day
- •Active hepatitis C infection. Patients positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
- •Infection requiring receipt of therapeutic oral or IV anti-microbials within 2 weeks of first study treatment. Patients receiving routine anti-microbial prophylaxis (for dental extractions/procedures) are eligible.
- •Significant cardiovascular disease such as New York Heart Association (NYHA) class II or greater, myocardial infarction within the previous 3 months of first study treatment, unstable arrhythmias, unstable angina. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist when appropriate.
- •Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowed.
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排除标准
- 未提供
研究组 & 干预措施
Bevacizumab And Atezolizumab Combination
Experimental
1200 mg of Atezolizumab intravenously x 3 weeks
15 mg/kg of Bevacizumab intravenously x 3 weeks.
One cycle will be 3 weeks in duration.
干预措施: Bevacizumab (Drug)
Bevacizumab And Atezolizumab Combination
Experimental
1200 mg of Atezolizumab intravenously x 3 weeks
15 mg/kg of Bevacizumab intravenously x 3 weeks.
One cycle will be 3 weeks in duration.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Best Overall Response Rate
时间窗: Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. The median (range) of treatment time was 9.5 (1-42) cycles, thus participants were assessed up to ~32 months .
The best overall response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesion: (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.
次要结局
- Median Progression Free Survival(Participants followed for up to 32 months.)
- 1-Year Overall Survival(1 year)
- Best Overall Response Rate by Histological Subtypes(Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. The median (range) of treatment time was 9.5 (1-42) cycles, thus participants were assessed up to ~32 months)
- Percentage of Participants With Treatment-related Adverse Events(Adverse events are measured continuously on treatment and up to thirty days after going off treatment (up to ~32 months).)
- 6-Month Progression-Free Survival by International Metastatic Renal Cell Carcinoma Risk Group(6 months)
- 1-Year Overall Survival by International Metastatic Renal Cell Carcinoma Risk Group(1 year)
- Duration of Response(Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. Off-treatment, patients are followed every 6 months for up to two year. Participants were followed up to 32 months.)
- Immune Related Best Overall Response Rate(Measured every 6 weeks while on treatment. Off-treatment, patients are followed every 6 months for up to two year. Participants were followed up to 32 months.)
- Mean Function Assessment of Cancer Therapy-Kidney Symptom Index-19 Score(Assessed at baseline, week 3, week 5, week 7, week 9, and end of therapy.)
- Brief Fatigue Inventory Score - Items 1-3(Assessed at baseline, week 9, week 15, week 21, week 27, and end of therapy.)
- 6-Month Progression-Free Survival by Histological Subgroups(6 months)
- 1-Year Overall Survival by Sarcomatoid Differentiation(1 year)
- 1-Year Overall Survival by Histological Subgroup(1 year)
- 6-Month Progression-Free Survival by Sarcomatoid Differentiation(6 months)
- Objective Response Rate by Sarcomatoid Differentiation(Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. The median (range) of treatment time was 9.5 (1-42) cycles, thus participants were assessed up to ~32 months .)
- Objective Response Rate by International Metastatic Renal Cell Carcinoma Risk Group(Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. The median (range) of treatment time was 9.5 (1-42) cycles, thus participants were assessed up to ~32 months .)
- 6-Month Progression-Free Survival by Prior Systemic Therapy(6 months)
- 1-Year Overall Survival by Prior Systemic Therapy(1 year)
- Objective Response Rate by Prior Systemic Therapy(Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. The median (range) of treatment time was 9.5 (1-42) cycles, thus participants were assessed up to ~32 months .)
研究者
Toni Choueiri, MD
Toni K. Choueiri, MD
Dana-Farber Cancer Institute
研究点 (4)
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