A Single Arm, Single Stage Phase II Trial of GSK1120212 and GSK2141795 in Persistent or Recurrent Cervical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Response Rate for the Combination of GSK1120212 (Trametinib) and GSK2141795 in Patients With Recurrent or Persistent Cervical Cancer.
研究概览
简要总结
This research study is evaluating the combination of two drugs called GSK1120212 (trametinib) and GSK2141795 as a possible treatment for recurrent or persistent cervical cancer. Trametinib and GSK2141795 are drugs that may stop cancer cells from growing. Trametinib is a MEK inhibitor - it blocks a protein called MEK that is commonly overactive in tumor cells. GSK2141795 is an AKT inhibitor which blocks a pathway in cancer cells that is commonly overactive in tumor cells called the PI3kinase pathway. In this research study, the investigator is looking to see whether the combination of Trametinib and GSK2141795 is useful in treating recurrent and persistent cervical cancer.
Additionally, the investigator is looking to see if participants whose tumors contain a particular genetic make-up will have better response to combination trametinib and GSK2141795. Participants' tumors will be tested for mutations in genes which could make some cancers more susceptible to trametinib and GSK2141795.
详细描述
Before the research starts (screening): The participant will be asked to undergo some screening tests or procedures to find out if they can be in the research study. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that the participant does not take part in the research study. If the participant has had some of these tests or procedures recently, they may or may not have to be repeated.
- A medical history, which includes questions about the participant's health, current medications, and any allergies.
- Physical exam, including height and weight
- An eye exam, by an eye specialist
- Performance status, the investigator will ask the participant questions about how they are able to carry on with your usual activities.
- Vital signs, including blood pressure, pulse, body temperature and respiratory rate
- An assessment of the participant's tumor by CT (Computerized Tomography) scan or MRI (Magnetic Resonance Imaging), of their chest, stomach area, and pelvis.
- Blood tests (approximately 2-3 tablespoons) including hematology, chemistry, liver function, kidney function, blood sugar levels, blood clotting levels
- Electrocardiogram (EKG), a test to check the participant's heart's rhythm
- Echocardiogram (ECHO), a test to check the participant's heart's structure and function.
- Serum pregnancy test if the participant are capable of becoming pregnant
If the results of the above tests show that the participant is eligible to participate in the research study, the participant will begin the study treatment. If the participant does not meet the eligibility criteria, the participant will not be able to participate in this research study.
If these tests show that the participant is eligible to participate in the research study, the participant will begin the study treatment. If the participant does not meet the eligibility criteria, the participant will not be able to participate in this research study.
Additional research procedures to be performed at the time of screening:
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Recurrent or metastatic cervical cancer of any histology
- •Measurable disease by RECIST 1.
- •Prior Therapy:
- •At least one prior chemotherapy regimen for management of cervical cancer. Radiation-sensitizing chemotherapy will not be counted as a systemic chemotherapy regimen
- •Patients can have received one additional regimen for treatment
- •No prior receipt of PI3K or RAS-ERK pathway inhibitors
- •Age ≥ 18 years
- •Life expectancy > 3 mos
- •ECOG performance status ≤ 2
- •Participants must have normal organ function as defined below:
- •Absolute Neutrophil Count (ANC)≥ 1,500/mcL
- •Platelets ≥ 100,000/mcL
- •Hemoglobin > 9.0/dL
- •AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN
- •Total Bilirubin within normal institutional limits
- •Albumin ≥ 2.5 g/dL
- •Creatinine ≤ upper limit of institutional normal or creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal or ≥ 50 mL/min 24-hour creatinine clearance
- •Normal LVEF
- •Normal fasting Blood Glucose
- •Availability of a formalin fixed paraffin embedded (FFPE) block of cancer tissue
- •Normal blood pressure (systolic < 140 mmHg and diastolic < 90 mmHg)
- •Women of childbearing potential must agree to use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- •Toxicities of prior therapy (excepting alopecia) should be resolved to ≤ grade 1
- •Ability to tolerate oral medications and no malabsorption
- •Ability to sign an informed consent
排除标准
- •No previous chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C,) or radiation therapy within 2 weeks prior to entering the study
- •No use of investigational agents nor have participated in an investigational trial within the past 4 weeks (or five half-lives whichever is shorter; with a minimum of 14 days from the last dose).
- •Presence of active GI disease that could affect GI absorption or predispose a subject to GI ulceration.
- •Evidence of mucosal of internal bleeding
- •Major surgery within the last 4 weeks
- •No Type 1 diabetes; however, patients with Type 2 diabetes are eligible if diagnosed ≥ 6 months prior to enrollment and if hemoglobin A1C (HbA1C) ≤ 8% at screening.
- •Symptomatic or unstable brain metastases or asymptomatic and untreated but > 1 cm in the longest dimension
- •Symptomatic or untreated leptomeningeal or spinal cord compression.
- •Individuals with a history of a different malignancy are ineligible except for the following circumstances: the following cancers are eligible if diagnosed and treated within the past 3 years: breast cancer in situ and basal cell or squamous cell carcinoma of the skin, stage I colon carcinoma confined to a polyp.
- •Any serious and/or unstable pre-existing medical disorders
- •Known infection with HIV, Hepatitis B Virus, or Hepatitis C Virus
- •Chronic use of drugs that are strong inhibitors or inducers of p450 CYP3A4
- •known immediate or delayed hypersensitivity reaction or idiosyncrasy to study drugs
- •History of interstitial lung disease or pneumonitis.
- •Presence of cardiac metastases
- •Subject with intra-cardiac defibrillators or pacemaker.
- •History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
- •History of RVO or CSR, or predisposing factors to RVO or CSR
- •Visible retinal pathology as assessed by ophthalmic exam
- •History or evidence of cardiovascular risk including any of the following
- •QTcF≥ 480 msec ( ≥ 500 msec for subject with bundle branch block)
- •History or evidence of current clinically significant uncontrolled arrhythmias. (Exception: controlled atrial fibrillation for >30 days prior to randomization)
- •History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months of study entry.
- •Class II or higher congestive heart failure.
研究组 & 干预措施
GSK1120212 (trametinib) and GSK2141795
GSK1120212 (trametinib) 1.5 mg QD + GSK2141795 50 mg QD in 28 day cycles
干预措施: GSK1120212 (trametinib) (Drug)
GSK1120212 (trametinib) and GSK2141795
GSK1120212 (trametinib) 1.5 mg QD + GSK2141795 50 mg QD in 28 day cycles
干预措施: GSK2141795 (Drug)
结局指标
主要结局
Response Rate for the Combination of GSK1120212 (Trametinib) and GSK2141795 in Patients With Recurrent or Persistent Cervical Cancer.
时间窗: 2 Years
Response rate will be assessed by RECIST version 1.1.
次要结局
- Mutation and Co-mutation Rates of Genes in the PI3K and RAS ERK Signaling Pathways in Recurrent Cervical Cancer Using High Throughput Targeted Mutational Analysis on Participant Tumor Samples.(2 Years)
- Duration of Progression-free (PFS)(2 Years)
- Toxicity of GSK1120212 (Trametinib) and GSK2141795 as Measured by the Number of Participants With Adverse Events(2 Years)
- Overall Survival(2 years)
研究者
Ursula A. Matulonis, MD
Principal Investigator
Dana-Farber Cancer Institute