A Phase I Dose-Escalation Study of Erlotinib in Combination With Pralatrexate in Subjects With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Erlotinib with Pralatrexate
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the combination of erlotinib and pralatrexate that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.
Pralatrexate is designed to block the body's ability to make folic acid, a protein that may help cancer tissue to develop and spread.
Erlotinib hydrochloride is designed to block proteins that are thought to cause cancer cells to grow. Erlotinib may help slow the growth of tumors.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of erlotinib and pralatrexate based on when you join this study.
Dose Escalation:
Several dose levels of erlotinib and pralatrexate will be tested. Three (3) to 6 participants will start at the lowest planned doses of erlotinib and pralatrexate. Each new group of 3-6 participants will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of erlotinib in combination with pralatrexate is found.
Dose Expansion:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Measurable or non-measurable disease.
- •Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months.
- •Patients must be at least 3 weeks after cytotoxic therapy and at least 5 half lives after their previous treatment or 3 weeks, whichever shorter, after biologic therapy. Patients may receive palliative radiotherapy immediately before or during treatment provided that not all target lesions are radiated.
- •Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%).
- •Patients must have normal organ and marrow function defined as: absolute neutrophil count >/=1,000/mL; platelets >/=100,000/mL; creatinine < 2.0; total bilirubin < 2.0; ALT(SGPT) </=3 X upper limit of normal (ULN); Exception for patients with liver metastasis: ALT(SGPT) </= 5 X ULN.
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
- •Ability to understand and the willingness to sign a written informed consent document.
- •For the MTD expansion cohort, patients will be eligible if they meet one of the following criteria: I. Have an epidermal growth factor receptor (EGFR)-sensitive mutation (as G719C in exon 18, E746-A750 in exon 90, L858R in exon 21) and have been previously treated with EGFR inhibitor therapy but have subsequently developed resistance, OR II. Have an EGFR-resistant mutation (as T790M in exon 20), OR III. Do not have an EGFR mutation, but have benefited from EGFR inhibitor therapy (including either >/=4 months of stable disease [SD] OR a >/= partial response [PR]).
- •Age >/= 12 years
排除标准
- •Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection requiring hospitalization; psychiatric illness/social situations that would limit compliance with study requirements.
- •Exclusion of patients with creatinine >2.0 and bilirubin > 2.
- •Patients with colorectal carcinoma with tumors that demonstrate a Kirsten rat sarcoma (KRAS) mutation.
- •Pregnant or lactating women.
- •Patients with a history of bone marrow transplant within the previous two years.
- •Patients with a known hypersensitivity to any of the components of the drug products.
- •Patients with major surgery within 30 days prior to entering the study.
研究组 & 干预措施
Erlotinib + Pralatrexate
Dose escalation group starting dose: Erlotinib 75 mg by mouth daily for a 28 day cycle. Starting dose of Pralatrexate 15 mg/m2 by vein on days 1, 8, and 15 of a 28 day cycle.
Dose expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.
干预措施: Erlotinib (Drug)
Erlotinib + Pralatrexate
Dose escalation group starting dose: Erlotinib 75 mg by mouth daily for a 28 day cycle. Starting dose of Pralatrexate 15 mg/m2 by vein on days 1, 8, and 15 of a 28 day cycle.
Dose expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.
干预措施: Pralatrexate (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Erlotinib with Pralatrexate
时间窗: 8 weeks
MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0. Grade 4 hematologic toxicity lasting 2 weeks or longer despite supportive care. Grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in NCI-CTCAE as attributable to therapy.
次要结局
- Tumor Response(8 weeks)