NCT01349933已完成2 期
Multicenter Phase II Study of MK-2206 in Previously Treated Patients With Recurrent and Metastatic Nasopharyngeal 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
- 21
- 试验地点
- 8
- 主要终点
- Proportion of Patients Alive and Progression-free
研究概览
简要总结
This phase II trial is studying how well Akt inhibitor MK2206 works in treating patients with recurrent or metastatic head and neck cancer. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the proportion of patients alive and progression-free at 6 months along with the confirmed response rate as a dual primary endpoint..
SECONDARY OBJECTIVES:
I. To evaluate best response and duration of response for patients treated with MK2206 (Akt inhibitor MK2206).
II. To evaluate the overall survival and progression-free survival (PFS) of patients treated with MK2206.
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
- •Histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma that has recurred at locoregional and/or distant sites, and is not amenable to potentially curative radiotherapy or surgery
- •Measurable disease according to the RECIST criteria
- •Progressed =< 24 months of receiving one or two prior line(s) of chemotherapy for recurrent disease, of which at least one line must contain platinum drugs such as cisplatin, carboplatin or oxaliplatin
- •ECOG performance status 0, 1, or 2
- •Hemoglobin >= 9 g/dL
- •ANC >= 1,500/μL
- •Platelet count >= 100,000/μL
- •Total bilirubin =< 2.5 times upper limit of normal (ULN)
- •ALT =< 2.5 times ULN (=< 5 times ULN for patients with liver metastases)
- •Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73 m^2
- •Ability to understand and the willingness to sign a written informed consent document
- •Willingness to donate blood for mandatory correlative research studies
- •Negative (serum) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
排除标准
- •Any of the following
- •Chemotherapy =< 4 weeks prior to registration
- •Radiotherapy =< 4 weeks prior to registration
- •Nitrosoureas or Mitomycin C =< 4 weeks prior to registration
- •Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •NOTE: Prior palliative radiotherapy to bone metastases is allowed =< 4 weeks prior to registration
- •Prior investigational agents =< 4 weeks prior to registration
- •Symptomatic brain metastases; NOTE: primary nasopharyngeal cancers that directly invade the skull base and extend into the infratemporal fossa(e) are not regarded as brain metastases and are not excluded
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in the study
- •Prior potent and moderate inhibitors and inducers of CYP3A4 =< 2 weeks prior to registration:
- •Drugs that are forbidden, potent inducers of CYP3A4: phenytoin, phenobarbitone, carbamazepine, barbiturate, rifampicin, St John's Wort.
- •Drugs that significantly affect metabolizing activity by way of enzyme inhibition of CYP3A4: ketoconazole, itraconazole, fluconazole, indinavir, ritonavir, erythromycin, cimetidine, clarithromycin
- •Unwillingness to go off other inducers and inhibitors of CYP3A4 during the first 2 cycles of MK-2206; NOTE: avoiding these drugs is critical during the first 2 cycles of MK-2206when blood samples are being taken for the correlative study unless there is an urgent medical need and alternatives are not available
- •Poorly controlled diabetes mellitus or insulin controlled diabetes; NOTE: As a general guide, patients with a fasting glucose level > 150 mg/dL (HbA1c <8%, > 8.3 mmol/L), or a random glucose level of >180mg/dL (> 10 mmol/L) is considered to have inadequately controlled diabetes and are not eligible for this study; however, such patients can become eligible in the future if their fasting glucose levels improve with medical treatment
- •QTc prolongation (defined as a QTc interval > 450 msec for males and >470 msec for females) or other significant ECG abnormalities; NOTE: patients with clinically significant cardiac conduction abnormalities should be excluded, these include left bundle branch block (LBBB), 2nd or 3rd degree AV block, bifascicular block, sick sinus syndrome, Wolff-Parkinson-white syndrome, sinus bradycardia (< 50bpm); however, patients with asymptomatic right bundle branch block (RBBB) or 1st degree AV block, in the absence of known cardiac disease (e.g. coronary, valvular) are not excluded
- •Uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection,
- •Symptomatic congestive heart failure,
- •Unstable angina pectoris,
- •Uncontrolled symptomatic cardiac arrhythmia,
- •Psychiatric illness/social situations that would limit compliance with study requirements
- •Diagnosed to have any of the following condition(s), and/or have undergone any one of the following procedure(s) =< 3 months prior to registration:
- •Symptomatic thrombotic or hemorrhagic cerebral vascular accident
- •Coronary bypass graft
- •Angioplasty
- •Myocardial infarction
- •Patients having continuing >= grade 2 adverse events (excluding alopecia) due to agents (chemotherapy or radiotherapy) administered > 4 weeks prior to registration based on Common Terminology Criteria for Adverse Events (CTCAE version 4.0) =< grade 1
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •NOTE: because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MK-2206, breastfeeding should be discontinued if the mother is treated with MK-2206; women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- •HIV-positive patients on combination antiretroviral therapy; NOTE: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MK-2206; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
- •Recent major surgery =< 4 weeks prior to registration (excluding the placement of vascular access), or minor surgery =< 2 weeks prior to registration
- •Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption) that impairs patients ability to swallow MK-2206 tablets
研究组 & 干预措施
Treatment (Akt inhibitor MK2206)
Experimental
Patients receive 200 mg Akt inhibitor MK2206 PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Akt inhibitor MK2206 (Drug)
结局指标
主要结局
Proportion of Patients Alive and Progression-free
时间窗: 6 months
The primary endpoint of this trial is the proportion of patients alive and progression-free at 6 months. Progression status is evaluated using RECIST version 1.1. A Progression is defined as either: At least one new malignant lesion, which also includes any lymph node that was normal at baseline (less than 1.0 cm short axis) and increased to greater than or equal to 1 cm short axis during follow up. Or, at least a 20% increase in sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes.
Confirmed Response Rate Defined to be a CR or PR Noted as the Objective Status on 2 Consecutive Evaluations at Least 4 Weeks Apart
时间窗: 6 months
Evaluated using RECIST version 1.1. A Complete Response (CR) requires disappearance of all target lesions and each target lymph node must have reduction in short axis to \<1.0 cm. A Partial Response (PR) requires at least a 30% decrease in the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation. The confirmed response rate is reported as the number of participants with confirmed responses divided by the number of evaluated participants.
次要结局
- Adverse Events Associated With the Agent Graded Based on CTCAE Version 4.0(Up to 30 days after completion of study treatment)
- Overall Survival(From registration to death due to any cause, assessed up to 3 years)
- Progression-free Survival(From registration to the first of either death due to any cause or progression, assessed up to 3 years)
- Best Response (Complete Response vs Partial Response vs Stable Disease vs Progression)(Up to 3 years)
- Duration of Response(The date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed up to 3 years)
研究者
研究点 (8)
Loading locations...
相似试验
已完成
2 期
Study of Akt Inhibitor MK2206 in Patients With Relapsed LymphomaAdult Nasal Type Extranodal NK/T-cell LymphomaAngioimmunoblastic T-cell LymphomaB-cell Adult Acute Lymphoblastic LeukemiaB-cell Chronic Lymphocytic LeukemiaCutaneous B-cell Non-Hodgkin LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueHepatosplenic T-cell LymphomaIntraocular LymphomaNodal Marginal Zone B-cell LymphomaNoncutaneous Extranodal LymphomaPeripheral T-cell LymphomaRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Cutaneous T-cell Non-Hodgkin LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaRefractory Hairy Cell LeukemiaSmall Intestine LymphomaSplenic Marginal Zone LymphomaT-cell Adult Acute Lymphoblastic LeukemiaT-cell Large Granular Lymphocyte LeukemiaTesticular LymphomaWaldenström MacroglobulinemiaAnaplastic Large Cell LymphomaNCT01258998National Cancer Institute (NCI)60
已完成
2 期
Akt Inhibitor MK2206 in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell LymphomaDiffuse Large B Cell LymphomaNCT01481129National Cancer Institute (NCI)22
已完成
2 期
Akt Inhibitor MK2206 in Treating Patients With Advanced Gastric or Gastroesophageal Junction CancerAdenocarcinoma of the Gastroesophageal JunctionDiffuse Gastric AdenocarcinomaGastric Intestinal Type AdenocarcinomaGastric Mixed AdenocarcinomaRecurrent Gastric CarcinomaNCT01260701National Cancer Institute (NCI)75
已完成
2 期
Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst CarcinomaRecurrent Oral Cavity Adenoid Cystic CarcinomaRecurrent Salivary Gland CarcinomaSalivary Gland Adenoid Cystic CarcinomaStage IVA Major Salivary Gland Cancer AJCC v7Stage IVA Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7Stage IVB Major Salivary Gland Cancer AJCC v7Stage IVB Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7Stage IVC Major Salivary Gland Cancer AJCC v7Stage IVC Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7NCT01604772National Cancer Institute (NCI)16
已完成
2 期
MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by SurgeryAdvanced Adult Hepatocellular CarcinomaLocalized Non-Resectable Adult Liver CarcinomaRecurrent Adult Liver CarcinomaRecurrent Gallbladder CarcinomaStage IV Distal Bile Duct CancerStage IV Gallbladder CancerUnresectable Extrahepatic Bile Duct CarcinomaUnresectable Gallbladder CarcinomaNCT01425879National Cancer Institute (NCI)8