NCT01240941撤回2 期
Phase II Trial of MK-2206 (an AKT Inhibitor) in Combination With Endocrine Therapy in Patients With Hormone Receptor Positive Breast Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Efficacy endpoint: Antitumor activity of MK-2206 when combined with exemestane +/- goserelin in pre- and post-menopausal patients with hormone receptor positive metastatic breast cancer, measured by clinical benefit rate.
研究概览
简要总结
This is a phase II Trial of MK-2206 in combination with Endocrine Therapy in patients with Hormone Receptor Breast Cancer. After the maximum tolerated dose is determined in the phase 1b trial (under a separate NCT number), efficacy will be evaluated among 17 patients.
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
- 未提供
排除标准
- •Patient who has had chemotherapy, radiotherapy, or biological therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day
- •If the patient has residual toxicity from prior treatment,toxicity must be less than or equal to Grade
- •Patients must be at least 4 weeks post major surgical procedure, and all surgical wounds must be fully healed.
- •Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day
- •Patient has known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2)off steroids that are used to minimize surrounding brain edema.
- •Patient has a primary central nervous system tumor.
- •Patient has known hypersensitivity to the components of study drug or its analogs.
- •Patient has a history or current evidence of clinically significant heart disease including:
- •Clinically significant congestive heart failure, unstable angina pectoris,
- •Clinically significant cardiac arrhythmia, history or current evidence of a myocardial infarction during the last 6 months,and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator.
- •Baseline QTc prolongation greater than 450 msec (Bazett's Formula). Medications included in Arizona CERT Lists 1 and 2 (Appendix D) must be excluded. The concomitant use of drugs that are associated with increased risk for QT prolongation should be avoided in patients with congenital long QT syndrome (Appendix D, Arizona CERT List 3). Similarly, the concomitant use of drugs that are weakly associated with QT prolongation should be generally avoided (Appendix D, Arizona CERT List 4). Arizona CERT List 3 and 4 drugs should be used at the discretion of the Investigator and restricted where applicable. Any therapy given with these drugs should be used with caution, and patients receiving these medications should be carefully monitored.
- •Patient with evidence of clinically significant bradycardia (heart rate less than 50 ), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2), or patients taking beta blockers, non-dihydropyridine calcium channel blockers, or digoxin.
- •Patient with uncontrolled hypertension (i.e., 160/90 mHg SiBP). Patients who are controlled on antihypertensive medication will be allowed to enter the study.
- •Patient at significant risk for hypokalemia (e.g., patients on high dose diuretics, or with recurrent diarrhea).
- •Patient with poorly controlled diabetes defined as HbA1C greater than 8%.
- •Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
- •Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- •Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
- •Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
- •Patient is known to be Human Immunodeficiency Virus (HIV)-positive
- •Patient has known history of Hepatitis B or C or active Hepatitis A.
- •Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
- •Patient is receiving treatment with oral corticosteroids (note: inhaled corticosteroids are permitted).
研究组 & 干预措施
MK-2206
Experimental
MK-2206 maximum tolerated dose found from Phase Ib trial (under a separate NCT number) taken orally on a weekly basis
干预措施: MK-2206 (Drug)
MK-2206
Experimental
MK-2206 maximum tolerated dose found from Phase Ib trial (under a separate NCT number) taken orally on a weekly basis
干预措施: Exemestane (Drug)
MK-2206
Experimental
MK-2206 maximum tolerated dose found from Phase Ib trial (under a separate NCT number) taken orally on a weekly basis
干预措施: Goserelin (Drug)
结局指标
主要结局
Efficacy endpoint: Antitumor activity of MK-2206 when combined with exemestane +/- goserelin in pre- and post-menopausal patients with hormone receptor positive metastatic breast cancer, measured by clinical benefit rate.
时间窗: 24 weeks (6 cycles)
Clinical benefit rate is defined as complete response + partial response + stable disease for at least 24 weeks following initiation of treatment.
次要结局
- The safety and tolerability of MK-2206 given in combination with exemestane +/- goserelin in pre- and post-menopausal patients with hormone receptor positive metastatic breast cancer.(every four weeks (1 cycle))
- Characterize the effect of MK-2206 in combination with exemestane +/- goserelin based on PI3K, AKT, and PTEN mutations(tumor blocks to be obtained prior to beginning the trial)
研究者
Vandana Abramson
Assistant Professor of Medicine, Medical Oncologist
Vanderbilt-Ingram Cancer Center
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