A Phase 1b Trial of LY2584702 in Combination With Erlotinib or Everolimus in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Recommended Dose for Phase 2 Studies
研究概览
简要总结
Study I3G-MC-JGCB (JGCB) is a multicenter, nonrandomized, open-label, dose-escalation Phase 1b study of LY2584702 in combination with either erlotinib or everolimus.
详细描述
Study JGCB will consist of the following parts:
Part 1 - Dose Escalation to maximum tolerated dose in each arm.
Arm A - LY2584702 + Erlotinib in participants with advanced or metastatic cancer.
Arm B - LY2584702 + Everolimus in participants with advanced or metastatic cancer.
Part 2 - Dose Confirmation of maximum tolerated dose from each arm in Part 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Dose Escalation portion (Part 1): have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease (including Non-Hodgkin's Lymphoma) for which no proven effective therapy exists.
- •Dose Confirmation portion (Part 2): have histological or cytological evidence of:
- •Arm A: advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.
- •Arm B: advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib, or advanced neuroendocrine tumors.
- •Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma.
- •Dose Escalation portion (Part 1): participants may have measurable or nonmeasurable disease.
- •Dose Confirmation portion (Part 2): participants must have measurable disease.
- •Have adequate organ function including:
- •Hematologic: absolute neutrophil count (ANC) greater than or equal to 1.5 x 10⁹/liters (L), platelets greater than or equal to 100 x 10⁹/L, and hemoglobin greater than or equal to 8 grams/deciliter (g/dL).
- •Hepatic: bilirubin less than or equal to 1.5 times upper limits of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling less than or equal to 5 times ULN are acceptable. Participants with bone metastases may enter with alkaline phosphatase values less than or equal to 5 times ULN, as long as other hepatic parameters meet inclusion criteria.
- •Renal: Serum creatinine less than or equal to 1.5 times ULN or calculated creatinine clearance >45 milliliter/minute (ml/mn).
- •Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- •Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 2 weeks (3 weeks for myelosuppressive agents) prior to study enrollment, and have recovered from the acute effects of therapy. At the discretion of the investigator, participants with prostate cancers progressing under luteinizing hormone-releasing hormone (LHRH) agonists therapy, and participants with adrenal carcinomas using mitotane, may have that treatment continued while receiving study drug.
排除标准
- •Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively.
- •Have serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study.
- •Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable and asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastasis is not required.
- •Concomitant treatment by strong cytochrome P450 (CYP) 3A4 inhibitors or CYP3A4 inducers.
- •Have an acute or chronic leukemia.
- •Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug. In addition, recipients of an allogeneic stem-cell transplant must have discontinued immunosuppressive therapy at least 24 hours before study drug administration with no more than Grade 1 acute graft-versus-host disease.
- •For Dose Confirmation portion (Part 2): have previously received erlotinib for Arm A or everolimus for Arm B.
研究组 & 干预措施
Arm A: LY2584702 + Erlotinib
Participants received 50 mg LY2584702 once daily (QD )+ 150 mg Erlotinib QD, 50 mg LY2584702 twice daily (BID) + 150 mg Erlotinib QD, 100 mg LY2584702 BID + 150 mg Erlotinib QD and 75 mg LY2584702 BID + 150 mg Erlotinib QD.
干预措施: LY2584702 (Drug)
Arm A: LY2584702 + Erlotinib
Participants received 50 mg LY2584702 once daily (QD )+ 150 mg Erlotinib QD, 50 mg LY2584702 twice daily (BID) + 150 mg Erlotinib QD, 100 mg LY2584702 BID + 150 mg Erlotinib QD and 75 mg LY2584702 BID + 150 mg Erlotinib QD.
干预措施: Erlotinib (Drug)
Arm B: LY2584702 + Everolimus
Participants received 50 mg LY2584702 QD + 10 mg Everolimus QD, 100 mg LY2584702 QD + 10 mg Everolimus QD and 50 mg LY2584702 BID + 10 mg Everolimus QD.
干预措施: LY2584702 (Drug)
Arm B: LY2584702 + Everolimus
Participants received 50 mg LY2584702 QD + 10 mg Everolimus QD, 100 mg LY2584702 QD + 10 mg Everolimus QD and 50 mg LY2584702 BID + 10 mg Everolimus QD.
干预措施: Everolimus (Drug)
结局指标
主要结局
Recommended Dose for Phase 2 Studies
时间窗: Baseline up to 6 cycles of 28 days
The recommended dose for the Phase 2 (Dose Confirmation Phase) study was determined by safety assessment. Doses were escalated following the assessment for toxicity based on Common Terminology Criteria for Adverse Events (CTCAE v4.0). Any adverse events (AE) that were possibly related to LY2584702 were considered toxicities. The Phase 2 dose of LY2584702 was not determined due to unacceptable toxicities of LY2584702 in combination with erlotinib or everolimus in Phase 1 of the study.
次要结局
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Response Rate (RR)](Baseline to disease progression or death or up to 6 cycles of 28 days)
- Pharmacokinetics, Maximum Observed Plasma Concentration (Cmax) of LY2584702(Cycle 1 Day 1 (C1 D1): predose, 0.5, 1, 2, 3, 5, 8 hours postdose and Cycle 1 Day 8 (C1 D8): predose, 0.5, 1, 2, 3, 5, and 8 hours postdose of 28-day cycle)
- Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Best Overall Response (BOR) (CR+PR+SD)](Baseline up to 112 Days)
- Clinically Significant Effects (Number of Participants With Adverse Events)(Baseline up to 7 months)
- Progression-Free Survival (PFS)(Baseline to disease progression or death or up to 166 days postbaseline)
- Pharmacokinetics, Area Under the Concentration Time Curve (AUC)(Cycle 1 Days 1 (C1 D1) and Cycle 1 Day 8 (C1 D8) of 28-day cycle)