NCT01936363已完成2 期
Phase II Randomized Double Blind Placebo Controlled Trial of Combination of Pimasertib With SAR245409 or of Pimasertib With SAR245409 Placebo in Subjects With Previously Treated Unresectable Low Grade Ovarian Cancer
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
- EMD Serono
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Objective Tumor Response
研究概览
简要总结
This is a double blind, randomized, placebo-controlled, 2-arm, Phase 2 trial investigating the efficacy and safety of combination therapy of pimasertib plus SAR245409 and pimasertib placebo administered once per day compared to pimasertib administered twice per day plus SAR245409 placebo administered once per day in participants with previously treated unresectable low-grade serous ovarian or peritoneal carcinoma or serous borderline ovarian or peritoneal tumors.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •The female participant had a diagnosis of one of the following: a) low-grade serous ovarian or peritoneal carcinoma, or grade 1 serous ovarian or peritoneal carcinoma or well-differentiated serous ovarian or peritoneal carcinoma or b) serous borderline ovarian or peritoneal tumor, ovarian or peritoneal tumor of low-malignant potential, ovarian or peritoneal atypical proliferative serous tumor that recurs as low grade serous carcinoma or has invasive peritoneal implants
- •The participant had at least one prior line of systemic therapy and had a tumor, which was not amenable to potentially curative surgical resection
- •The participant had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •The participant had read and understood the written informed consent form (ICF) and was willing and able to gave informed consent, fully understood the requirements of the trial and was willing to comply with all trial visits and assessments, including completion of patient-reported measures. Consent must be given before any trial related activities
- •Women of childbearing potential must had a negative serum pregnancy test at the screening visit
- •Women of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to screening, during and at least 3 months after the last dose of trial medication
- •Other protocol defined inclusion criteria may apply
排除标准
- •The participant had previously been treated with a PI3K inhibitor and taken off treatment due to treatment related AEs
- •The participant had been previously treated with a Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor
- •Any anti-cancer therapy or treatment incorporating chemotherapy, immunotherapy, hormonal therapy, or biologic therapy within 28 days of the start of trial treatment or within 5 times the half-life of such treatment, whichever was shorter. Treatment with nitrosoureas or mitomycin C were exceptions to this for which a treatment interval of at least 6 weeks was required
- •The participant had not recovered from toxicity due to prior therapy to baseline level or National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) Grade 1 or less (except alopecia). Residual chemotherapy-induced neuropathy grade less than equal to (<=) 2 was permitted
- •The participant had poor organ and marrow function as defined in the protocol
- •The participant had creatine phosphokinase (CPK) elevation NCI CTCAE grade greater than equal to (>=) 2, and/or a previous history of myositis or rhabdomyolysis
- •The participant had difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the trial drug. Participants requiring total parenteral nutrition were to be excluded
- •The participant had a history of delayed healing/open wounds or diabetic ulcers
- •The participant had a history of congestive heart failure, unstable angina, myocardial infarction, cardiac conduction abnormalities including Fridericia corrected QT interval (QTcF) prolongation of > 480 milliseconds (ms) or a pacemaker, clinically relevant impaired cardiovascular function (New York Heart Association (NYHA) class III/IV) or stroke within 3 months prior to enrollment
- •The participant had a history of retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), uveitis or retinal vein occlusion (RVO), or had other relevant abnormalities identified on screening ophthalmologic examination, which might increase the risk of serous retinal detachment (SRD) or RVO
- •The participant had a history of uncontrolled intercurrent illness including but not limited to an active infection, hypertension, or uncontrolled diabetes (e.g. glycosylated hemoglobin >= 8 percent [%]) that would limit compliance with treatment requirements
- •Any previous malignancy treated with curative intent and the participant had been disease free for less than 5 years prior to randomization, with exception of carcinoma-in-situ of the cervix, squamous carcinoma of the skin, basal cell carcinoma of the skin
- •Other protocol defined exclusion criteria may apply
研究组 & 干预措施
Pimasertib (once daily) plus SAR245409
Experimental
干预措施: Pimasertib once daily (Drug)
Pimasertib (once daily) plus SAR245409
Experimental
干预措施: Pimasertib placebo (Drug)
Pimasertib (once daily) plus SAR245409
Experimental
干预措施: SAR245409 (Drug)
Pimasertib (twice daily) plus SAR245409 placebo
Experimental
干预措施: SAR245409 placebo (Drug)
Pimasertib (twice daily) plus SAR245409 placebo
Experimental
干预措施: Pimasertib twice daily (Drug)
结局指标
主要结局
Objective Tumor Response
时间窗: From randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months
Objective tumor response was defined as the presence of at least one Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to more than (\<) 10 millimeter (mm). Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Progression-Free Survival(Time from randomization until first observation of progressive disease or death, assessed up to 52 months)
- Percentage of Participants With Disease Control(Randomization until disease progression or death assessed every 8 weeks up to week 32, and thereafter every 12 weeks up to 52 months)
- Overall Survival(Time from randomization until death, assessed up to 52 months)
- Health Related Quality of Life (HrQoL) Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)(Baseline up to disease progression or withdrawal, assessed up to 52 months)
- Health Related Quality of Life (HrQoL) Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Ovarian-Specific Module Quality of Life Questionnaire Ovarian Cancer Module (QLQ-OV28)(Baseline up to disease progression or withdrawal, assessed up to 52 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation of Treatment and Death(First dose of study drug up to 52 months)
- Maximum Plasma Concentration (Cmax) After Dose of Pimasertib and SAR245409(Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43)
- Area Under the Curve (AUC) After Dose of Pimasertib and SAR245409(Pre-dose Hour 0.5, 1.5, 4.5 8 post dose on Day 15, 29, 43)
- Molecular Alterations in MAPK and/or PI3K Signaling Pathway Components/Modulators in Tumor Tissue and Blood(Screening visit (day -28 to 1))
研究者
研究点 (1)
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