Phase Ib Study of Dovitinib in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Plus Carboplatin in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Recommended phase II dose of combination regimen
研究概览
简要总结
This is a phase Ib dose escalation study of dovitinib given in combination with either gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. Patients with advanced solid tumors, for whom treatment with gemcitabine plus cisplatin or carboplatin would otherwise be warranted, will be enrolled. The dose of dovitinib will be escalated in successive cohorts using standard "3+3" dose escalation rules. Patients will continue treatment, in the absence of prohibitive toxicity, until disease progression. The study will define the recommended phase II dose of these combination regimens.
详细描述
This is a phase Ib study of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. This study will utilize standard 3+3 dose escalation rules to define the recommended phase II dose. Dose escalation will proceed independently in the two cohorts (cisplatin cohort: gemcitabine + cisplatin + dovitinib; carboplatin cohort: gemcitabine + carboplatin + dovitinib). Patients will receive treatment for up to 6 cycles, in the absence of toxicity, until disease progression
Primary Objective:
To determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin.
Secondary Objectives:
- To determine the response rate to treatment as per Response Evaluation Criteria in Solid Tumors (RECIST)
- To determine the toxicity of treatment at per the Common Terminology for Adverse Events (CTCAE v4)
- To determine the pharmacokinetics of dovitinib in combination with gemcitabine plus cisplatin or carboplatin.
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
- •Written informed consent and HIPAA authorization for release of personal health information.
- •Age ≥ 18 years at the time of consent.
- •Karnofsky Performance Status of ≥ 70%.
- •Advanced/metastatic solid tumor for which treatment with gemcitabine plus carboplatin or gemcitabine plus cisplatin would otherwise be warranted.
- •Prior treatment with chemotherapy is permitted. Patients must not have received more than three prior chemotherapeutic regimens.
- •Adequate organ function as determined by the following laboratory values:
- •Hemoglobin (Hgb) ≥ 9 g/dL
- •Platelets ≥ 100 x 109/L
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •Creatinine of ≤ 1.5 OR Calculated creatinine clearance of ≥ 60 cc/min for the cisplatin cohort.
- •Calculated creatinine clearance of ≥ 30 cc/min for the carboplatin cohort.
- •Bilirubin ≤ 1.5 x ULN
- •Aspartate aminotransferase (AST, SGOT) ≤ 1.5 ULN
- •Alanine Aminotransferase (ALT, SGPT) < 1.5 ULN
- •INR ≤ 1.5 and a PTT within normal limits
- •LVEF assessed by 2-D echocardiogram (ECHO) > 50% or lower limit of normal or multiple gated acquisition scan (MUGA) > 45% or lower limit of normal
排除标准
- •Prior treatment with more than three prior chemotherapy regimens.
- •Has had major surgery within 30 days of starting the study treatment
- •Have active CNS metastases.
- •No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
- •Prior cancer treatment must be completed at least 30 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxic effects of the regimen.
- •Prior radiation therapy must be completed at least 30 days prior to being registered for protocol therapy.
- •Pregnant or breastfeeding.
- •Clinically significant infections as judged by the treating investigator.
- •Impaired cardiac function or clinically significant cardiac diseases
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- •Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin
- •Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception.
- •Fertile males not willing to use contraception
研究组 & 干预措施
Cisplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts.
干预措施: Cisplatin (Drug)
Carboplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Recommended phase II dose of combination regimen
时间窗: Within the first 21 days of treatment
The primary objectives of this study are to determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus carboplatin or cisplatin.
次要结局
- Antitumor activity(After every 2 cycles (42 days) of combination therapy up to 3 years)
研究者
Matthew Galsky
Principal Investigator
Icahn School of Medicine at Mount Sinai