A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology Of PI3-Kinase Inhibitor GDC-0941 In Combination With Either Paclitaxel And Carboplatin (With or Without Bevacizumab) or Pemetrexed, Cisplatin, And Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 主要终点
- Number of Participants with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) GDC-0941 administered with one of three planned regimens: Arm A: paclitaxel and carboplatin in bevacizumab-ineligible NSCLC patients, Arm B: paclitaxel, carboplatin, and bevacizumab in bevacizumab-eligible NSCLC patients and Arm C: pemetrexed, cisplatin, and bevacizumab in bevacizumab-eligible, non-squamous NSCLC patients.
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
- •Histologically or cytologically documented NSCLC with advanced disease (Stage IIIb not eligible for chemoradiotherapy or Stage IV or recurrent disease)
- •Adequate organ function as assessed by laboratory tests
- •Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)
排除标准
- •More than one anti-cancer regimen (chemotherapy or radiotherapy) for advanced NSCLC prior to initiation of study treatment
- •Any adjuvant or neoadjuvant anti-cancer therapy within a specified timeframe prior to first study treatment
- •History of Grade >= 3 fasting hyperglycemia or diabetes requiring regular medication
- •Active autoimmune disease, active infection requiring IV antibiotics, or other current uncontrolled illness
- •History of clinically significant cardiac or pulmonary dysfunction
- •History of malabsorption syndrome or other condition that would interfere with enteral absorption
- •Clinically significant history of liver disease
- •Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents
- •Known brain metastases that are untreated, symptomatic, or require therapy
- •Pregnancy, lactation, or breastfeeding
研究组 & 干预措施
GDC-0941+Paclitaxel+Carboplatin
Bevacizumab-ineligible non-small cell lung cancer (NSCLC) participants may receive up to 6 cycles (21-day cycle) of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941
干预措施: GDC-0941 (Drug)
GDC-0941+Paclitaxel+Carboplatin
Bevacizumab-ineligible non-small cell lung cancer (NSCLC) participants may receive up to 6 cycles (21-day cycle) of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941
干预措施: carboplatin (Drug)
GDC-0941+Paclitaxel+Carboplatin
Bevacizumab-ineligible non-small cell lung cancer (NSCLC) participants may receive up to 6 cycles (21-day cycle) of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941
干预措施: paclitaxel (Drug)
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab
Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
干预措施: GDC-0941 (Drug)
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab
Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
干预措施: bevacizumab (Drug)
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab
Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
干预措施: carboplatin (Drug)
GDC-0941+Paclitaxel+Carboplatin+Bevacizumab
Bevacizumab-eligible NSCLC particpants may receive up to 6 cycles of combination chemotherapy with paclitaxel and carboplatin along with GDC-0941 and bevacizumab.
干预措施: paclitaxel (Drug)
GDC-0941+Pemetrexed+Cisplatin
Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\n
干预措施: GDC-0941 (Drug)
GDC-0941+Pemetrexed+Cisplatin
Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\n
干预措施: bevacizumab (Drug)
GDC-0941+Pemetrexed+Cisplatin
Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\n
干预措施: cisplatin (Drug)
GDC-0941+Pemetrexed+Cisplatin
Bevacizumab-ineligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941.\n
干预措施: pemetrexed (Drug)
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab
Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\n
干预措施: GDC-0941 (Drug)
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab
Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\n
干预措施: bevacizumab (Drug)
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab
Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\n
干预措施: cisplatin (Drug)
GDC-0941+Pemetrexed+Cisplatin+Bevacizumab
Bevacizumab-eligible NSCLC participants may receive up to 6 cycles of combination chemotherapy with pemetrexed and cisplatin along with GDC-0941 and bevacizumab.\n
干预措施: pemetrexed (Drug)
结局指标
主要结局
Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Days 1 to 22 of Cycle 1
Percentage of Participants with Adverse Events (AEs)
时间窗: Up to approximately 5.5 years
次要结局
- Maximum Plasma Concentration of Paclitaxel(Cycle 1 Day 2: Pre-paclitaxel infusion, end of paclitaxel infusion, 0.5, 1 and 2 hours post-paclitaxel infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-paclitaxel Day 2 infusion)
- Maximum Plasma Concentration of Carboplatin(Cycle 1 Day 2: Pre-carboplatin infusion, end of Carboplatin infusion, 0.5, 1.5 hours post-carboplatin infusion\n\n)
- Maximum Plasma Concentration of Pemetrexed(Cycle 1 Day 2: Pre-pemetrexed infusion, end of pemetrexed infusion, 1, 3 hours post-pemetrexed infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-pemetrexed Day 2 infusion\n\nd be "Yes".)
- Maximum Plasma Concentration of Cisplatin(Cycle 1 Day 2: Pre-cisplatin infusion, end of cisplatin infusion, 3 hours post-cisplatin infusion; Cycle 1 Day 3: Pre-GDC-0941 dose, 24 hours post-pemetrexed Day 2 infusion\n\n)
- Percentage of Participants with Objective Response (Complete or Partial Response), as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)(Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)\n\n)
- Duration of Response, as Assessed Using RECIST\n\n\n(Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years))
- Progression-free Survival (PFS), as Assessed Using RECIST\n(Screening, Days 15 to 21 of Cycles 2, 4, 6, 9, and every 3 cycles thereafter (up to approximately 5.5 years)\n\n)
- Maximum Plasma Concentration of GDC-0941(Cycle 1 Days 1 and 2: Pre-GDC-0941 dose, 1, 2, 3 and 4 hours post-GDC-0941 dose; Cycle 1 Days 3 and 9: Pre-GDC-0941 dose; 30 days after last dose of study treatment (up to approximately 5.5 years))