A Phase I Dose-Escalation Study of Erlotinib in Combination With Bortezomib in Subjects With Advanced Cancer. Companion Study to Umbrella Protocol 2007-0638.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of Tarceva (erlotinib hydrochloride) that can safely be given in combination with Velcade (bortezomib). The safety of this drug combination will also be studied.
详细描述
The Study Drugs:
Erlotinib hydrochloride and bortezomib are both designed to block proteins that are thought to cause cancer cells to grow. These drugs may help slow the growth of tumors.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of erlotinib hydrochloride and bortezomib based on when you join the study. Up to 4 dose levels of this study drug combination will be tested. There will be 3-6 participants enrolled at each dose level of the study drug combination.
The first group of participants will receive the lowest dose level of erlotinib hydrochloride (Group 1). If all of Group 1 tolerate that dose level, the next group (Group 2) will receive a higher dose. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen (Groups 2-4). This will continue until the highest tolerable dose of the study drug combination is found. However, if Group 1 did not tolerate the first dose level, the next group will receive a lower dose (called Dose Level -1). If that dose level is still intolerable, the third group will receive an even lower dose (called Dose Level -2).
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have had no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- •Measurable or non-measurable disease.
- •Patients must be >/= 6 wks beyond treatment with a nitrosourea or mitomycin-C, >/= 4 wks beyond other chemotherapy or external beam radiation therapy (XRT), and must have recovered to </= Grade 1 toxicity for any treatment-limiting toxicity resulting from prior therapy. (Exception: patients may have received palliative low dose XRT one week before treatment provided it is not given to the only targeted lesions).
- •(continued from above) Also, patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 wks, whichever is shorter, from the last day of treatment.
- •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 >/=50,000/mL; creatinine </= 2 X upper limit of normal (ULN); total bilirubin </= 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; 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 EGFR-sensitive mutation and have been previously treated with EGFR inhibitor therapy but have subsequently developed resistance, OR (II) Have an EGFR-resistant mutation, 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]).
排除标准
- •Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection; altered mental status or psychiatric illness/social situations that would limit compliance with study requirements and/or obscure study results.
- •Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg on medication).
- •Patients with clinically significant cardiovascular disease: history of cardiovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
- •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 unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.
- •Patients with major surgery within 30 days prior to entering the study.
研究组 & 干预措施
Erlotinib + Bortezomib
Up to 4 dose levels of study drug combination tested with 3-6 participants enrolled at each dose level. Erlotinib beginning dose of 150 mg taken by mouth daily for 21-day cycle. Bortezomib beginning dose of 1. mg/m^2 by vein over about 1-5 minutes on Days 1, 4, 8, and 11 of each 21-day cycle.
干预措施: Erlotinib Hydrochloride (Drug)
Erlotinib + Bortezomib
Up to 4 dose levels of study drug combination tested with 3-6 participants enrolled at each dose level. Erlotinib beginning dose of 150 mg taken by mouth daily for 21-day cycle. Bortezomib beginning dose of 1. mg/m^2 by vein over about 1-5 minutes on Days 1, 4, 8, and 11 of each 21-day cycle.
干预措施: Bortezomib (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 21 days
MTD defined as highest dose studied in which incidence of dose limiting toxicity (DLT) was less than 33%. DLT defined as any Grade 3 or 4 non-hematologic toxicity defined in the NCI CTC v3.0, even if expected and believed related to study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by the NCI-CTCAE), despite supportive care; any 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 the NCI-CTCAE that is attributable to the therapy.
Tumor Response
时间窗: Evaluation of response after two 21-day cycles of treatment
Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a \>/= 25% decrease in cancer antigen 125 (CA125) for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e. decrease in size by 10% or more, or a decrease in the tumor density, as measured in Hounsfield units (HU), by more than or equal to 15%.
次要结局
未报告次要终点