A Phase 1b/2a Three-Part Open-Label Multicenter Study to Evaluate the Safety and Efficacy of LY2880070 as Monotherapy and in Combination With Gemcitabine in Patients With Advanced or Metastatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 229
- 试验地点
- 16
- 主要终点
- Maximum Tolerated Dose(s)
研究概览
简要总结
The main purpose of this 3-part study is to evaluate the safety and efficacy of the study drug known as LY2880070 in participants with advanced or metastatic solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have an estimated life expectancy of greater than or equal to (≥)12 weeks
- •Have adequate organ function
- •Have received 1-4 prior systemic therapies for locally advanced or metastatic disease
- •Agree to use medically approved contraceptives during the study and for 3 months following the last study treatment
- •All females must have a negative serum pregnancy test result, and females of child-bearing potential must have a negative urine pregnancy test result, prior to the first study treatment
- •Have tumor lesions considered measurable by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Must be, in the judgment of the investigator, an appropriate candidate for experimental therapy, and no standard therapy would confer clinical benefit
- •Must have evidence of cancer (solid tumors, excluding glioblastoma and primary brain tumor) that is advanced or metastatic
- •For the Metabolism Phenotype Arm in Part A, participants must have a Cytochrome P450 (CYP2D6) poor metabolizer phenotype
- •Have advanced or metastatic colorectal cancer, triple negative breast cancer (per American Society of Clinical Oncology-College of American Pathology guidelines), epithelial ovarian cancer, endometrial, soft tissue sarcoma, pancreatic cancer
- •For TNBC:
- •Recurrent/refractory Triple Negative Breast Cancer (TNBC) defined as any beast cancer that expresses <1% estrogen receptor (ER) and <1% progesterone receptor (PR) and is Her2 negative
- •For Colorectal (CRC):
- •Must have histologically confirmed advanced or metastatic colorectal cancer
- •For Ovarian Cancer:
- •Must have histologically confirmed advanced or metastatic epithelial ovarian cancer
- •Must be eligible to receive Gemzar (GEM) and not refractory to GEM/carboplatin
- •Must have the ability to tolerate GEM
- •May have received GEM as previous therapy
- •For Endometrial cancer:
- •Must have histologically confirmed endometrial cancer that is metastatic or locally advanced
- •Must have failed at least 1 prior chemotherapy
- •Must have histologically confirmed STS that is metastatic or locally advanced
- •Patients with gastrointestinal stromal tumors (GIST) must have failed a KIT inhibitor
- •Must have failed at least 1 prior chemotherapy
- •For Pancreatic Cancer:
- •Must have histologically confirmed pancreatic cancer that is metastatic or locally advanced
- •Must have failed at least 1 prior chemotherapy regimen
- •For Part C
- •Participants with high grade serous ovarian cancer (HGSOC) will be screened for specific genetic signatures
排除标准
- •Have received treatment with an investigational drug which has not received regulatory approval within 21 days of first study treatment
- •Have symptomatic central nervous system (CNS) metastasis
- •Females who are pregnant or nursing
- •Have known positive test results of human immunodeficiency virus, or have chronic active hepatitis A, B or C
- •Have a corrected QT interval (QTcB) greater than (>) 470 milliseconds (msec) (female) or >450 msec (male), or a history of congenital long QT syndrome
- •Have had a bone marrow transplant
- •Have participated in this study, or are currently enrolled in another clinical study of an investigational medicinal product
- •Have had radiation therapy to >25% of bone marrow
- •For Part B
- •Have a history of another active cancer within the past year, except cervical cancer in situ, in situ carcinoma of the bladder, basal cell carcinoma of the skin, or another in situ carcinoma that is considered cured
研究组 & 干预措施
Part A: LY2880070
Multiple oral doses of LY2880070 during 21-day cycles
干预措施: LY2880070 (Drug)
Part A: LY2880070 with Gemcitabine
Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles
干预措施: LY2880070 (Drug)
Part A: LY2880070 with Gemcitabine
Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles
干预措施: Gemcitabine (Drug)
Part A: LY2880070 (Metabolism Phenotype)
Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers
干预措施: LY2880070 (Drug)
Part B: LY2880070 and Gemcitabine (Breast)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: LY2880070 (Drug)
Part B: LY2880070 and Gemcitabine (Breast)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: Gemcitabine (Drug)
Part B: LY2880070 and Gemcitabine (Colorectal)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: LY2880070 (Drug)
Part B: LY2880070 and Gemcitabine (Colorectal)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: Gemcitabine (Drug)
Part B:LY2880070 and Gemcitabine (Ovarian)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: LY2880070 (Drug)
Part B:LY2880070 and Gemcitabine (Ovarian)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: Gemcitabine (Drug)
Part B: LY2880070 and Gemcitabine (Endometrial)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: LY2880070 (Drug)
Part B: LY2880070 and Gemcitabine (Endometrial)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: Gemcitabine (Drug)
Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS))
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: LY2880070 (Drug)
Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS))
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: Gemcitabine (Drug)
Part B: LY2880070 and Gemcitabine (Pancreatic)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: LY2880070 (Drug)
Part B: LY2880070 and Gemcitabine (Pancreatic)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: Gemcitabine (Drug)
Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: LY2880070 (Drug)
Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)
Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Maximum Tolerated Dose(s)
时间窗: Baseline through Cycle 1 (Estimated up to 21 days)
次要结局
- Number of dose limiting toxicities (DLTs)(Baseline through Cycle 1 (Estimated up to 21 days))
- Change from baseline in white blood cell count(Baseline to 24 hours post dose (up to Day 20 in Cycle 1))
- Change from baseline in neutrophil count(Baseline to 24 hours post dose (up to Day 20 in Cycle 1))
- Duration of objective response(Baseline to study completion (estimated up to 4 years))
- Area under the plasma concentration versus time curve from time zero to 24 hours post-dose (AUC0-24)(Baseline to 24-hours post dose (up to Day 20 in Cycle 1))
- Peak plasma concentration (Cmax)(Baseline to 24 hours post-dose (up to Day 20 in Cycle 1))
- Time to reach maximum plasma concentration (tmax)(Baseline to 24 hours post dose (up to Day 20 in Cycle 1))
- Overall survival(Baseline up to 1 year)
- Number of participants with tumor response (objective response rate) as measured by the Response Evaluable Criteria in Solid Tumors (RECIST v.1.1)(Baseline to study completion (estimated up to 4 years))
- Best response(Baseline to study completion (estimated up to 4 years))
- Progression free survival(Baseline to study completion (estimated up to 4 years))
- Change from baseline in lymphocyte count(Baseline to 24 hours post dose (up to Day 20 in Cycle 1))