An Open-Label Randomized Phase II Trial Comparing Gemcitabine and Carboplatin With and Without P276-00 in Subjects With Metastatic Triple Negative Breast Cancer, With a Phase I Run-in of Escalating Dose of P276-00 Added to Gemcitabine and Carboplatin
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 4
- 主要终点
- Median Progression free survival
研究概览
简要总结
P276-00 is a novel, potent, small-molecule, flavone-derived Cdk 4 D1, Cdk1 B, and Cdk9 T inhibitor, with potent cytotoxic effects against chemosensitive and chemoresistant cancer cell lines.This study is planned to compare efficacy of the standard chemotherapy regimen of gemcitabine and carboplatin when administered with or without P276-00 in subjects with advanced triple negative breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Females of age ≥18 years.
- •Histologically documented metastatic triple negative breast cancer (any triple negative breast cancer for Phase I)
- •Two or fewer chemotherapy regimens for advanced disease (no limit of prior regimens for Phase I)
- •ECOG performance score of 1 or less
- •Presence of measurable disease by RECIST 1.1 criteria (not for the Phase I portion)
- •Ability to understand and the willingness to sign a written informed consent document (ICD)
- •Full recovery from all prior treatment toxicities to Common Terminology Criteria for Adverse Events (CTCAE V.4) Grade ≤ 1
排除标准
- •Prior chemotherapy or biologic/targeted anticancer agents within 4 weeks of study drug administration
- •Prior radiation therapy within 6 weeks of study drug administration
- •Subject with known active CNS metastases and/or carcinomatous meningitis. However, subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases (2) off steroids that are used to minimize surrounding brain edema.
- •Prior therapy with gemcitabine or a platinum agent (not for the Phase I part)
- •Prior therapy with a Cdk/cyclin inhibitor or any flavones derivative
- •QTc interval >450 msec (using Fridericia's formula)
- •Any acute illness including uncontrolled diabetes, symptomatic or otherwise uncontrolled cardiac disease (coronary artery disease, arrhythmias, congestive heart failure) or other illness that in the judgment of the investigator would introduce additional medical risks
- •Visceral crisis including extensive liver disease with>50% parenchymal involvement or lymphangitic pulmonary disease
- •History of other prior malignancies except for properly treated basal cell or squamous cell carcinoma of skin, in situ cervical cancer, or in situ breast cancer
- •Expected survival of less than 3 months
- •Hemoglobin <9.0 gm/dL
- •Absolute neutrophil count <1500/mm3
- •Platelet count <100,000/mm3
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >3 × institutional upper limit of normal (ULN)
- •Total bilirubin, >1.5 × institutional ULN
- •Serum creatinine >1.5 mg/dL
- •Subjects with known infection with human immunodeficiency virus (HIV), tuberculosis, Hepatitis C or Hepatitis B
- •Pregnant or lactating women
- •Women of childbearing potential not willing to use approved methods of contraception after signing the ICD, during the entire study and for at least 4 weeks after completion of study or following withdrawal from the study
研究组 & 干预措施
Gemcitabine and Carboplatin
Gemcitabine 1000 mg/m2/day on Days 1 & 8 and carboplatin at AUC 2 on Days 1 and 8 every 21 days.
干预措施: Gemcitabine and Carboplatin (Drug)
P276-00 along with Gemcitabine and carboplatin
P276-00 will be administered at starting dose of 100 mg/m2/day (and higher if tolerated) in 200 mL of 5% dextrose as an iv infusion over 30 minutes, on Days 1 to 5, along with gemcitabine 1000 mg/m2/day and carboplatin at AUC 2 on Days 1 & 8 every 21 days.In Phase 2 component, P276-00 will be administered at recommended phase II dose of P276-00 in combination with standard dose of gemcitabine and carboplatin.
干预措施: P276-00 along with Gemcitabine and carboplatin (Drug)
结局指标
主要结局
Median Progression free survival
时间窗: 1 year and above
The primary efficacy endpoint will be median progression-free survival (PFS), defined as the time from the beginning of study treatment to the occurrence of documented disease progression or recurrence, or death from any cause
次要结局
- Progression Free Survival at 6 months(at 6 months)
- Objective response rate(upto 3 years and above)
- Duration of response(upto 3 years and above)
- Overall survival (OS)(at 3 years)
- Overall survival at 6 months(at 6 months)