NCT01974258撤回1 期
A PHASE Ib, OPEN-LABEL STUDY EVALUATING THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF ONARTUZUMAB IN COMBINATION WITH VEMURAFENIB AND/OR COBIMETINIB IN PATIENTS WITH ADVANCED SOLID MALIGNANCIES
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Safety: Incidence of adverse events (AE)
研究概览
简要总结
This study will evaluate the maximum tolerated dose and dose-limiting toxicities of vemurafenib and/or cobimetinib when used with onartuzumab in cancer patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Adult patients >/= 18 years of age.
- •Patients with histologically confirmed, BRAFV600-mutant, unresectable, locally advanced or metastatic solid malignancies. OR
- •Patients with a histologically confirmed, KRAS-mutant, Stage IV colorectal adenocarcinoma, or KRAS-mutant metastatic non-small-cell lung carcinoma. OR
- •Patients with histologically confirmed BRAFV600-mutant unresectable Stage IIIC or Stage IV metastatic melanoma.
- •Valid MET IHC test result.
- •Measurable disease per Response Evaluation Criteria in Solid Tumors v1.1
- •ECOG performance status of 0 or
- •For BRAFV600-mutant cancers:
- •Previously untreated for their melanoma or previously treated for their melanoma but without prior exposure to any HGF, MET, BRAF, or MEK inhibitor therapy
- •BRAFV600-mutant solid malignancies other than melanoma for which standard therapy does not exist has proven to be ineffective or intolerable or is considered inappropriate.
- •Patients must not have had prior exposure to HGF, MET, BRAF, or MEK inhibitor therapy.
- •For KRAS-mutant cancers:
- •mCRC patients must have received therapeutic regimens including oxaliplatin, irinotecan, 5-FU, and bevacizumab, or determined to be ineligible for these treatments. Patients must not have had prior exposure to HGF, MET, BRAF, or MEK inhibitor therapy.
- •Metastatic NSCLC patients must have received platinum-based doublet chemotherapy or determined to be ineligible for this regimen. Patients must not have had prior exposure to HGF, MET, BRAF, or MEK inhibitor therapy.
- •Consent to provide tumor tissue for biomarker analyses.
- •Life expectancy >/= 12 weeks.
- •Fully recovery from the effects of any major surgery or significant traumatic injury within 14 days from the first dose of study treatment.
- •Adequate hematologic and end organ function, as defined by clinical laboratory results.
- •Use of effective form(s) of contraception as defined by protocol during the course of this study and for at least 6 months after study drug discontinuation.
排除标准
- •Palliative radiotherapy or experimental therapy within 28 days prior to first dose of study drug treatment.
- •Major surgical procedure or significant traumatic injury from 28 days prior to first dose of study drug treatment until end of study.
- •History of another malignancy in the previous 5 years, unless cured by surgery alone and continuously disease free. Exceptions include appropriately treated cervical carcinoma in situ, non-melanoma skin carcinoma, Stage I uterine cancer, localized prostate cancer that has been treated surgically and is presumed cured, or other malignancies with an expected curative outcome.
- •Brain metastasis or spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated central nervous system (CNS) metastases or spinal cord compression without evidence of clinically stable disease for more than 14 days.
- •Note: Patients with treated CNS metastases who are asymptomatic and on a stable dose of corticosteroids for more than 14 days prior to Cycle 1 Day 1 are eligible.
- •For patients given cobimetinib: Evidence of visible retinal pathology that is considered a risk factor for neurosensory detachment, retinal vein occlusion, or neovascular macular degeneration, or of conditions that are risk factors for retinal vein occlusion.
- •Current or history of clinically significant cardiac or pulmonary dysfunction.
- •Lack of recovery to Grade 1 or better from adverse events due to investigational or other agents administered more than 28 days prior to enrollment, except for alopecia.
- •Current severe, uncontrolled systemic disease.
- •Inability or unwillingness to swallow pills.
- •History of malabsorption or other condition that would interfere with gastrointestinal absorption of study drug.
- •History of clinically significant liver disease, current alcohol abuse, or known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).
- •Severe (Grade 3 and above) active infection at enrollment, or other serious underlying medical conditions.
- •Required medication known to cause edema and/or cardiac failure.
- •Active autoimmune disease.
- •Uncontrolled ascites requiring weekly, large-volume paracentesis for 3 consecutive weeks prior to enrollment.
研究组 & 干预措施
Dose-expansion: onartuzumab + vemurafenib + cobimetinib
Experimental
干预措施: Onartuzumab (Drug)
Dose-expansion: onartuzumab + cobimetinib
Experimental
干预措施: Cobimetinib (Drug)
Dose-expansion: onartuzumab + cobimetinib
Experimental
干预措施: Onartuzumab (Drug)
Dose-expansion: onartuzumab + vemurafenib
Experimental
干预措施: Onartuzumab (Drug)
Dose-expansion: onartuzumab + vemurafenib
Experimental
干预措施: Vemurafenib (Drug)
Dose-expansion: onartuzumab + vemurafenib + cobimetinib
Experimental
干预措施: Cobimetinib (Drug)
Dose-expansion: onartuzumab + vemurafenib + cobimetinib
Experimental
干预措施: Vemurafenib (Drug)
Dose-finding: onartuzumab + vemurafenib + cobimetinib
Experimental
干预措施: Cobimetinib (Drug)
Dose-finding: onartuzumab + vemurafenib + cobimetinib
Experimental
干预措施: Onartuzumab (Drug)
Dose-finding: onartuzumab + vemurafenib + cobimetinib
Experimental
干预措施: Vemurafenib (Drug)
结局指标
主要结局
Safety: Incidence of adverse events (AE)
时间窗: 24 to 36 months
Safety: Incidence of anti-therapeutic antibodies against onartuzumab.
时间窗: 24 to 36 months
Safety: Incidence of dose-limiting toxicities (DLTs) of vermurafenib and/or cobimetinib used in combination with onartuzumab.
时间窗: 24 to 36 months
次要结局
- Efficacy: Overall response rate(24 to 36 months)
- Efficacy: Overall survival(24 to 36 months)
- Pharmacokinetics: Maximum concentration (Cmax) of onartuzumab(24 to 36 months)
- Efficacy: Duration of response(24 to 36 months)
- Pharmacokinetics: Maximum concentration (Cmax) of vemurafenib(24 to 36 months)
- Pharmacokinetics: Maximum concentration (Cmax) of cobimetinib(24 to 36 months)
- Efficacy: Progression-free survival(24 to 36 months)
研究者
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