NCT01473901已完成1 期
A Phase I, Two-stage, Multi-center, Open Label, Dose-escalation Study of BKM120 in Combination With Adjuvant Temozolomide and With Concomitant Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 4
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
This clinical study will assess the doses of BKM120 appropriate for patients with newly diagnosed glioblastoma when given in combination with radiotherapy and temozolomide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patient is ≥ 18 years of age on the day of consent signature
- •Patient with histologically demonstrated, previously untreated glioblastoma
- •Patient may have received initial treatment for GBM as follows:
- •For patients enrolled into Stage I, they must have received at least 75% of planned radiotherapy (60 Gy) with temozolomide treatment during the concomitant phase have documentation that the patient's absolute neutrophil count (ANC) is ≥ 1.5 x 109/L, platelet count is ≥ 100 x 109/L, and there was no CTC grade 2 or above nonhematological toxicity (except for alopecia, nausea, vomiting) during the concomitant phase treatment be within ≥ 4 weeks but ≤ 6 weeks following the completion of temozolomide in the concomitant phase
- •For patients enrolled into Stage II, they must be within ≥ 2 weeks but ≤ 6 weeks after primary GBM resection/biopsy The patient must have recovered from the definitive surgical procedure for GBM
- •Patient is able to be assessed by periodic dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scan
- •Patient has Karnofsky performance status >= 60
- •Patient has adequate bone marrow and organ function
排除标准
- •Patient has received previous treatment with PI3K and/or mTOR inhibitors for GBM or for pre-existing neoplasm transformed to GBM. Patient has received any prior anti-neoplastic therapy for BKM, except for the treatment allowed in inclusion criteria
- •Patient has any tumor progression after definitive GBM resection/ biopsy, except for the transformation from previous low grade glioma. Patient with a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer)
- •Patient who had not recovered to grade 1 or better from any adverse events (except alopecia, nausea, vomiting) related to previous antineoplastic therapy before screening procedures are initiated, as allowed in inclusion criteria
- •Patient has any of the following baseline mood disorders (not attributable to GBM) as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 12 in the PHQ- 9 or a cut-off of ≥ 15 in the GAD-7 mood scale for reasons not attributable to GBM; or selects a positive response of '1, 2, 3' to question number 9 regarding potential for suicidal thoughts or ideation in the PHQ-9 (independent of the total score of the PHQ-9)
- •Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
- •Active severe personality disorders (defined according to DSM-IV). Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
- •≥ CTCAE grade 3 anxiety
- •Patient who is concurrently using any other approved or investigational anti-neoplastic agent
- •Patient who has undergone the following invasive procedures: Major surgical procedure, open biopsy or significant traumatic injury < 14 days prior to starting study drug or has not recovered from side effects of such therapy, anticipation of need for invasive surgical procedure during the course of the study, biopsy within 7 days prior to starting study drug
- •Patient has poorly controlled diabetes mellitus (HbA1c > 8%)
- •Patient is currently receiving increasing or chronic treatment with corticosteroids or another immunosuppressive agent
- •Patient is currently receiving an enzyme inducing anti-epileptic drug. The patient must have discontinued EIAED therapy for at least two weeks prior to starting study drug. Non-enzyme inducing anti-epileptic medication is allowed, except those listed in the protocol
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
BKM120 + Temozolomide (Concomitant Phase)
Experimental
Cranial radiation: Days 1 - 5 every 7 days for 42 days60 Gy in 30 fractions; Temozolomide: 75 mg/m2 Daily, orally; BKM120: 0, or 40, or 60, or 80 mg/d Daily, orally or Days 1-5 every 7 days, orally
干预措施: BKM120 + temozolomide (Drug)
BKM120 + temozolomide with/without radiotherapy
Experimental
Adjuvant phase cycle 1:
Temozolomide 150 mg/m2 - Days 1 - 5 every 28 days Daily; BKM120 60, or 80, or 100 mg/d;
Adjuvant phase cycle 2+:
Temozolomide 200* mg/m2 - Day 1 ~ 5 every 28 days Daily BKM120 0, or 40, or 60, or 80 or 100 mg/d
干预措施: BKM120 +temozolomide with/without radiotherapy (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: Concomitant phase (42 days), adjuvant phase cycle 1 (28-day cycle), adjuvant phase cycles 2 (28-day cycle)
Per DLT criteria as defined in protocol
次要结局
- No of participants with Adverse events based on abnormal laboratory results, abnormal electrocardiogram (ECG) findings(Baseline, 30 days post the last BKM120 treatment)
- Objective response rate (ORR)(Baseline, 18 months after first BKM120 treatment)
- Progression free survival (PFS)(at 12 months and at 18 months)
- Overall survival (OS)(Until death or consent withdrawal)
- Plasma concentration-time profiles and basic pharmacokinetic parameters of BKM120 and temozolomide (Cmax, tmas, AUC, half-life)(baseline, Day 1, 8, 15, 28 in concomitant phase, Cycle 1 Day 1, 5 and Cycle 2 Day1, 5 at adjuvant phase (28-day per cycle))
研究者
研究点 (4)
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