MATCH Treatment Subprotocol M: Phase II Study of MLN0128 (Tak-228) in Patients With Tumors With TSC1 or TSC2 Mutations
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 49
- 试验地点
- 2
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This phase II MATCH treatment trial tests how well MLN0128 (TAK-228) works in treating patients with cancer that has certain genetic changes called TSC1 or TSC2 mutations. MLN0128 (TAK-228) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
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
- •Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
- •Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
- •Patients must have a TSC1 or TSC2 mutation as determined via the MATCH Master Protocol
- •Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must NOT have any of the following cardiac criteria:
- •Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block, corrected QT interval (QTc) interval > 480 milliseconds)
- •Uncontrolled hypertension (i.e. systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg) are not eligible. Use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed
- •Known pulmonary hypertension
- •Patients must not have known hypersensitivity to MLN0128 (TAK-228) or compounds of similar chemical or biologic composition
- •Patients must not have known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection, but may have had previously treated and successfully eradicated hepatitis C virus (HCV)
- •Patients must have none of the following within six months of receiving the first dose of MLN0128 (TAK-228): ischemic, myocardial or cerebrovascular event, class III or IV heart failure, placement of pacemaker, or pulmonary embolism
- •Patients must have no manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228)
- •Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
- •Brain metastases which have been treated
- •No evidence of disease progression for >= 1 months before the first dose of study drug
- •No hemorrhage after treatment
- •Off-treatment with dexamethasone for 4 weeks before administration of the first dose of MLN0128 (TAK-228)
- •No ongoing requirement for dexamethasone or anti-epileptic drugs
- •Patients meeting the following criteria for concomitant medications prior to starting MLN0128 (TAK-228) are not eligible for the study:
- •Patients who use a proton pump inhibitor (PPI) within 7 days before receiving the first dose of study drug
- •Patients who would require treatment with PPIs throughout the trial
- •Patients who would need to take H2 receptor antagonists within 24 hours of the first dose of study drug NOTE Strong CYP1A2 inhibitors and CYP inducers should be administered with caution, at the discretion of the investigator. Alternative treatments, if available, should be considered.
- •Patients must not have known treatment with systemic corticosteroid within one week prior to the first administration of study drug
- •Patients must not have uncontrolled diabetes mellitus. Controlled diabetes is defined as: Glycosylated hemoglobin (HbA1c) < 7.0%, or fasting serum glucose (=< 130 mg/dL)
- •Patients must not have fasting triglycerides >= 300 mg/dL
- •Patients must not have had prior treatment with other known TORC1/2 inhibitors, including:
- •GSK2126458
- •DS3078(a)
- •PF-05212384
- •Palomid-529
- •GDC0980 (apitolisib)
- •LY30223414
- •MLN0128 (TAK-228)
- •Patients must not have other clinically significant co-morbidities that, in the opinion of the investigator, would limit compliance with study requirements
- •Fertility and developmental studies with MLN0128 (TAK-228) have not been conducted. On the basis of potential hazard of other mTOR inhibitors (i.e., rapamycin and other rapalogs) on the developing fetus, women of childbearing age should avoid becoming pregnant while taking MLN0128 (TAK-228). For this reason, women of child-bearing potential and men must agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 120 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Men must agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug
- •Patients who are known to be HIV-positive are not eligible for this study
排除标准
- 未提供
研究组 & 干预措施
Treatment (sapanisertib [MLN0128 (TAK-228)])
Patients receive sapanisertib (MLN0128 [TAK-228]) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.
干预措施: Biopsy Procedure (Procedure)
Treatment (sapanisertib [MLN0128 (TAK-228)])
Patients receive sapanisertib (MLN0128 [TAK-228]) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.
干预措施: Biospecimen Collection (Procedure)
Treatment (sapanisertib [MLN0128 (TAK-228)])
Patients receive sapanisertib (MLN0128 [TAK-228]) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.
干预措施: Computed Tomography (Procedure)
Treatment (sapanisertib [MLN0128 (TAK-228)])
Patients receive sapanisertib (MLN0128 [TAK-228]) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (sapanisertib [MLN0128 (TAK-228)])
Patients receive sapanisertib (MLN0128 [TAK-228]) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.
干预措施: Sapanisertib (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to 3 years
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response: * For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks) * For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks) * For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)
次要结局
- Overall survival (OS)(From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years)
- 6-month progression free survival (PFS)(From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months)
- Progression free survival(From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years)