An Umbrella Protocol for Histology-Independent, Phase I Modular Study Based on Epidermal Growth Factor Receptor (EGFR) Mutation Status: Using Erlotinib Alone or in Combination With Cetuximab, Bortezomib, or Dasatinib to Overcome Resistance
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) and toxicity profiles via a brief initial "run-in"/dose escalation.
研究概览
简要总结
The goal of this screening portion of this clinical research study is to learn if you are eligible to take part in a clinical research study using Tarceva (erlotinib hydrochloride) and either Erbitux (cetuximab), Velcade (bortezomib), or Sprycel (dasatinib).
If the results of the screening portion of this clinical research study show that you are eligible to take part in one of the studies described above, the study drug that you will be assigned to take will depend on the results of biomarker analysis performed as a part of the screening tests described below. Biomarkers are chemical "markers" in the blood/tissue that may be related to how your body might react to the study drug.
详细描述
Drug Administration and Study visits for Erlotinib hydrochloride:
If you will be taking Erlotinib hydrochloride in this study, you will take Erlotinib hydrochloride by mouth daily at least 1 hour before eating and 2 hours after eating. You will have study visits once a month. If you continue to be on study longer than 2 cycles, study visits may become less frequent.
At these visits, the following tests and procedures will be performed:
- Your performance status will be recorded.
- You will be asked to list any drugs you may be taking, including over-the-counter drugs.
- You will be asked about any symptoms you may have.
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 2 teaspoons) will be collected for routine tests
After the first 8 weeks on study, you will have a CT or MRI scan to check the status of the disease. You will have a CT or MRI scan every 8 to 12 weeks after that.
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
- 18 Years 至 —（Adult, Older Adult）
- 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.
- •Patients must have tumor tissue available, either from an archival specimen, or from a recent biopsy, to be analyzed for EGFR mutation. Patients must sign consent for the umbrella protocol prior testing for EGFR mutation. Patients will be eligible if they have an EGFR-sensitive mutation, OR if they have an EGFR-resistant mutation, OR if they 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]).
- •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.
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 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 who will be on treatment arm consisting of erlotinib and dasatinib should not be taking any drugs that are potent inhibitors or inducers of CYP34A
- •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 Hydrochloride
Those eligible for umbrella of studies and have not received Erlotinib hydrochloride in past, will first receive Erlotinib hydrochloride alone.
干预措施: Erlotinib Hydrochloride (Tarceva) (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) and toxicity profiles via a brief initial "run-in"/dose escalation.
时间窗: Continous reassessment during dose level/cycles (28 days)
MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle (induction phase). DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0, even if expected and believed related to the 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.
次要结局
未报告次要终点