NCT02293005已完成2 期
Phase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma
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
- 28
- 试验地点
- 1
- 主要终点
- Disease Control Rate at 4 Months
研究概览
简要总结
Objectives:
Objectives
The primary objective of this study is to:
To assess 4-month disease control rate (DCR) in pre-treated patients with unresectable malignant pleural mesothelioma (MPM) treated with alisertib
The secondary objectives of this study are to:
To assess the response rate (confirmed and unconfirmed complete + partial responses) To assess the progression-free survival. To assess overall survival. To evaluate the side effects and toxicities associated with this treatment regimen.
To collect archival tissue, blood, pleural effusion fluid and plasma for correlative studies.
Exploratory Objectives:
To collect archival or new tissue, blood and pleural effusion fluid for correlative studies. Tissue biomarkers to be evaluated include aurora kinase pathway and c-myc gene amplification.
Next generation sequencing (NGS) will be conducted on adequate tumor tissue specimens.
详细描述
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take alisertib tablets by mouth 2 times each day on Days 1-7 of each 21-day study cycle. You must take your doses of alisertib at least 6 hours apart with 1 cup (about 8 ounces) of water.
If you miss or vomit a dose of alisertib, do not retake that dose. Wait and take the next dose as scheduled.
Study Visits:
On Day 1 of Cycles 1-3 and then every odd-numbered cycle after that (Cycles 5, 7, 9 and so on):
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
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- •Female subject is either: post-menopausal for at least one year before the screening visit, or surgically sterilized, or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and at least 1 month after the last dose of alisertib.
- •Male subject, even if surgically sterilized (ie, status postvasectomy), agrees to use an acceptable barrier method for contraception (condom with a spermicidal agent), or completely abstain from heterosexual intercourse during the entire study treatment period through 4 months after the last dose of alisertib.
- •Absolute neutrophil count (ANC) > 1500/mm3, platelets > 100,000/mm3, Hgb > 9 g/dL.
- •Total bilirubin </= 1.5 x upper limit of normal (ULN), SGOT (AST) and SGPT (ALT)< 2.5 x ULN. AST and/or ALT may be up to 5X ULN if with known liver mets
- •Adequate renal function as defined by: Calculated creatinine clearance must be >/= 30 mL/minute
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Pathologic diagnosis of malignant mesothelioma (any primary site is acceptable)
- •Have unresectable malignant mesothelioma (any histology)
- •Received at least one prior pemetrexed-based chemotherapy for unresectable disease, unless within 3 months of receiving platinum-pemetrexed therapy for neoadjuvant or adjuvant treatment that has been unsuccessful.
- •Up to 4 prior lines of systemic therapy (biologic or chemotherapy) are allowed. Maintenance therapy after 4-6 cycles of front-line chemotherapy is still considered 1 line of therapy and is not considered 2 separate therapies.
- •Patients must have measurable disease by modified RECIST or RECIST. Examinations for assessment of measurable disease must have been completed within 28 days prior to registration.
- •Patient must be >/= 18 years of age
排除标准
- •Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
- •Prior allogeneic bone marrow or organ transplantation
- •Known GI disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib. Examples include, but are not limited to partial gastrectomy, history of small intestine surgery with significant removal of the small intestine, and celiac disease
- •Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease. Patients who use CPAP or BIPAP at night and have controlled sleep apnea syndrome are allowed.
- •Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed.
- •Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
- •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- •Female subject who is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum Beta-human chorionic gonadotropin (Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Patient has received other investigational drugs with 14 days before enrollment
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
- •Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- •Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of alisertib and during the study.
- •Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion. For guidance in defining active infection for hepatitis B, please refer to the WHO guidelines
- •Prior administration of an Aurora A kinase-targeted agent, including alisertib
- •Receipt of corticosteroids within 7 days prior to the first dose of study treatment, unless patient has been taking a continuous dose of no more than 15 mg/day of prednisone for at least 1 month prior to first dose of study treatment. Low dose steroid use for the control of nausea and vomiting will be allowed. Topical steroid use is permitted. Inhaled steroids are permitted.
- •Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to alisertib.
- •Administration of myeloid growth factors or platelet transfusion within 14 days prior to the first dose of study treatment.
- •Persons who are incarcerated at time of enrollment (e.g., prisoners) or likely to become incarcerated during the study.
研究组 & 干预措施
Alisertib
Experimental
Alisertib administered by mouth at 50 mg twice a day for 7 days in each treatment cycle, followed by a 14-day, treatment-free period.
干预措施: Alisertib (Drug)
结局指标
主要结局
Disease Control Rate at 4 Months
时间窗: 4 months from treatment started
Patients who are free of disease progression at 4 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Progression Free Survival (PFS)(From treatment start to death/progression or last follow-up, whichever come first assessed up to 25 months.)
- Overall Response Rate(From treatment start, every 6 weeks until progression, death, withdrawal of consent or study completion an average of 25 months)
- Overall Survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 35 months)
研究者
研究点 (1)
Loading locations...
相似试验
终止
1 期
Alisertib (MLN8237) in Combination With Weekly Paclitaxel in East Asian Patients With Advanced Solid TumorsAdvanced Solid TumorsOvarian CancerSmall Cell Lung CancerNCT02367352Millennium Pharmaceuticals, Inc.9
已完成
2 期
Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or LeukemiaPreviously Treated Childhood RhabdomyosarcomaRecurrent Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Myeloid LeukemiaRecurrent Childhood Kidney NeoplasmRecurrent Childhood Malignant Germ Cell TumorRecurrent Childhood RhabdomyosarcomaRecurrent Childhood Soft Tissue SarcomaRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal TumorRecurrent NeuroblastomaRecurrent OsteosarcomaHepatoblastomaNCT01154816Children's Oncology Group118
已完成
2 期
Study to Compare Alisertib With Paclitaxel vs. Paclitaxel Alone in Metastatic or Locally Recurrent Breast CancerBreast CarcinomaBreast TumorsMalignant Neoplasm of BreastBreast CancerNCT02187991US Oncology Research169
已完成
2 期
Alisertib With or Without Fulvestrant in Treating Patients With Locally Advanced or Metastatic, Endocrine-Resistant Breast CancerEstrogen Receptor StatusHER2/Neu NegativeInvasive Breast CarcinomaPostmenopausalStage III Breast CancerStage IIIA Breast CancerStage IIIB Breast CancerStage IIIC Breast CancerStage IV Breast CancerNCT02860000Mayo Clinic96
已完成
1 期
Alisertib, Abiraterone Acetate and Prednisone in Treating Patients With Hormone-Resistant Prostate CancerAdenocarcinoma of the ProstateHormone-resistant Prostate CancerRecurrent Prostate CancerStage IV Prostate CancerNCT01848067Sidney Kimmel Cancer Center at Thomas Jefferson University9