NCT02296476终止2 期
A Phase IIa Trial With Dose Optimization of OTX015, a Small Molecule Inhibitor of the Bromodomain and Extra-terminal (BET) Proteins, in Recurrent Glioblastoma Multiforme (GBM) Patients
Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)0 个研究点目标入组 12 人开始时间: 2014年10月29日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 主要终点
- Progression-free Survival (PFS) at 6 Months
研究概览
简要总结
A study of single-agent birabresib (MK-8628) (formerly known as OTX015) in recurrent GBM after standard front-line therapy failure.
The first phase of the study (dose escalation) will determine the maximum tolerated dose (MTD). MTD assessment will be based using dose-limiting toxicities (DLTs) observed during the first 28 days of treatment.
The second phase of the study (expansion cohort) will assess efficacy as measured by the progression-free survival rate at 6 months (PFS-6) as determined by an independent central review committee.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Has signed informed consent obtained prior to initiation of any study-specific procedures and treatment. Participants registered for this trial must be treated and followed at the participating centers
- •Has a histologically confirmed diagnosis of de novo glioblastoma multiforme (World Health Organization grade IV astrocytoma) with unequivocal tumor recurrence by magnetic resonance imaging (MRI) scan (performed on a stable steroid dosage received for at least 5 days) following front-line treatment with surgical resection, cranial radiotherapy and temozolomid. Participants who do not undergo surgical resection as part of front-line therapy due to anatomical location based on neurosurgeon's assessment will be permitted if a confirmatory tumor biopsy was performed
- •Has at least one measurable and/or non-measurable lesion as per Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al., 2010)
- •Is at least 18 years old
- •Has a life expectancy >3 months;
- •Has a Karnofsky performance status (KPS) ≥70%
- •Has adequate bone marrow reserve, renal and liver function as demonstrated by the following: absolute neutrophil count ≥1.5 x109/L; platelet count ≥150 x109/L; hemoglobin ≥10 g/dL; creatinine 2 x the upper limit of normal (ULN) or calculated creatinine clearance ≥30 mL/min (Cockroft and Gault formula or Modification of Diet in Renal Disease [MDRD] formula for participants aged >65 years); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN, and total bilirubin ≤ULN
- •Has an interval of ≥2 weeks since surgical resection, ≥4 weeks since chemotherapy (≥6 weeks for nitrosoureas), and ≥12 weeks since radiotherapy completion when starting study treatment. Participants with recent tumor resection must have an MRI within 48 hours post-surgery
- •Has archived tumor pathology specimen (paraffin-embedded or frozen block)
排除标准
- •Has had prior antineoplastic treatment for recurrent disease including vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors and cytotoxic agents
- •Is unable to undergo MRI because of non-compatible devices
- •Is unable to swallow oral medications or presence of a gastrointestinal disorder (e.g. malabsorption, resection) deemed to jeopardize intestinal absorption
- •Has persistent grade >1 clinically significant toxicities related to prior antineoplastic therapies
- •Has a history of prior or concomitant malignancies within 5 years of study entry (other than excised non-melanoma skin cancer or cured in situ cervical carcinoma). Male participants with concurrent controlled hormone dependent prostate cancer are allowed
- •Has other serious illness or medical conditions which in the investigator's opinion could hamper understanding of the study by the participant, the participant's compliance to study treatment, participant's safety, or interpretation of study results. These include (but are not restricted to) existence of significant neurologic or psychiatric disorders impairing the ability to obtain consent, uncontrolled infection and known HIV positivity
- •Is taking enzyme-inducing antiepileptic drug (EIAED)
- •Is taking strong CYP3A4 interacting drugs
- •Is participating in another clinical trial or treatment with any investigational drug within 4 weeks prior to first study treatment administration, or 5 half-lives of previously administered drugs, whichever is longer
- •Is pregnant or breast feeding
- •Is not using effective contraception while on study treatment if a participant of child-bearing potential
研究组 & 干预措施
Birabresib 80 mg
Experimental
Participants received 80 mg of oral birabresib administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles.
干预措施: Birabresib (Drug)
Birabresib 120 mg
Experimental
Participants received 120 mg of oral birabresib administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles.
干预措施: Birabresib (Drug)
Birabresib 160 mg
Experimental
Participants received 160 mg of oral birabresib administered once daily (in a fasted state) every day in a 28-day cycle for up to 6 cycles.
干预措施: Birabresib (Drug)
结局指标
主要结局
Progression-free Survival (PFS) at 6 Months
时间窗: Month 6
Progression-free survival was the time from the start of study treatment to the date of clinical or radiographic evidence of progressive disease according to Response Assessment in Neuro-Oncology (RANO) 2010 criteria or death. Progression, as assessed by RANO 2010, was defined as a ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. PFS at 6 months was measured as the percentage of participants who were alive and progression-free at Month 6. PFS at 6 months was calculated for all participants who were actively enrolled in the study at the 6-month time point.
次要结局
- Overall Survival (OS)(Up to 6 Months)
- Progression-free Survival(Up to 6 Months)
- Objective Response Rate (ORR)(Up to 6 Months)
- Number of Participants Who Experienced at Least One Adverse Event (AE)(Up to 6 Months)
- Duration of Response (DOR)(Up to 6 Months)
- Number of Participants Who Experienced at Least One Toxicity Grade 3-5 AE(Up to 6 Months)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to 6 Months)
- Observed Maximum Concentration (Cmax) of MK-8628(Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours postdose)
- Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1(Up to Cycle 1 (Up to 28 days))
- Apparent Total Body Clearance (Cl/F) of MK-8628(Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours)
- Time to Maximum Concentration (Tmax) of MK-8628(Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours postdose)
- Observed Minimum Concentration (Cmin) of MK-8628(Predose on Days 29 and 57)
- Apparent Terminal Half-Life (t1/2) of MK-8628(Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours)
- Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628(Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours)
- Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞)(Day 1: Predose and 0.25, 1, 2, 3, 7, and 8 hours)
研究者
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