A Phase I Trial of Regorafenib and Cetuximab in Patients With Advanced Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Treatment with Regorafenib and Cetuximab
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 regorafenib and cetuximab that can be given to patients with advanced solid tumors. The safety and effectiveness of this drug combination will also be studied.
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 the study drugs based on when you join the study.
Up to 5 dose level combinations of regorafenib and cetuximab will be tested. Up to 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level combination. Each new group will receive a higher dose of either regorafenib or cetuximab than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose combination of regorafenib and cetuximab are found.
Once the highest tolerable dose combination is found, up to 10 more participants may be enrolled. This group (called the Dose Expansion group) is enrolled to help researchers study the safety and effectiveness of this dose level combination.
Study Drug Administration:
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
- •Patient must be >= 12 years of age and > 40kgs.
- •Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- •Patients must have evaluable or measurable disease by RECIST criteria for solid tumors.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Patients must be >/= 4 weeks beyond treatment with any chemotherapy or radiotherapy, and must have recovered to </= grade 2 toxicity for any treatment-limiting toxicity of prior therapy. (Exception: patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, ribs, sternum, scapulae, vertebrae or skull were not included in the radiotherapy field). Also, patients who have received non-chemotherapeutic biologic agents will need to wait at least five half-lives or four weeks, whichever is shorter, from the last day of treatment. Exception: No washout of cetuximab or regorafenib is required for patients who have received prior cetuximab or regorafenib and have recovered from any treatment-related toxicities to Grade </=
- •ECOG performance status </= 2 (Karnofsky >/= 60%).
- •Patients must have: leukocytes >/= 3,000/mL; absolute neutrophil count >/= 1,000/mL; platelets >/=100,000/mL; creatinine </= 2 X ULN; total bilirubin </= 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; AST (SGOT) and ALT(SGPT) </= 5 X ULN. Patients should not have received any platelet transfusions in the last 4 weeks before screening date.
- •Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose.
排除标准
- •KRAS mutated colorectal cancer.
- •Major surgery within 28 days prior to the first dose of study medication.
- •Pregnant or lactating women.
- •Patients with hemoptysis within 28 days prior to entering the study.
- •Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- •Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day
- •Patients with clinically significant cardiovascular disease: 1). History of CVA within 6 months; 2). Myocardial infarction or unstable angina within 6 months; 3). Unstable angina pectoris; 4). New York Heart Association Class III or greater congestive heart failure.
- •Patients with untreated or progressing brain metastases.
- •Patients who had radiation to greater than 25% marrow in the past 5 years.
研究组 & 干预措施
Regorafenib + Cetuximab
Dose Escalation Group Starting Dose of Regorafenib: 80 mg by mouth once a day for 21 days (5 days on and 2 days off) in a 28 days cycle. Dose Expansion Group Starting Dose of Regorafenib : MTD from Dose Escalation Group.
Dose Escalation Group Starting Dose of Cetuximab: 200 mg/m2 initial dose, then 150 mg/m2 by vein over about 1-2 hours on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting Dose of Cetuximab: MTD from Dose Escalation Group.
Symptom questionnaire completed at each study visit.
干预措施: Regorafenib (Drug)
Regorafenib + Cetuximab
Dose Escalation Group Starting Dose of Regorafenib: 80 mg by mouth once a day for 21 days (5 days on and 2 days off) in a 28 days cycle. Dose Expansion Group Starting Dose of Regorafenib : MTD from Dose Escalation Group.
Dose Escalation Group Starting Dose of Cetuximab: 200 mg/m2 initial dose, then 150 mg/m2 by vein over about 1-2 hours on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting Dose of Cetuximab: MTD from Dose Escalation Group.
Symptom questionnaire completed at each study visit.
干预措施: Cetuximab (Drug)
Regorafenib + Cetuximab
Dose Escalation Group Starting Dose of Regorafenib: 80 mg by mouth once a day for 21 days (5 days on and 2 days off) in a 28 days cycle. Dose Expansion Group Starting Dose of Regorafenib : MTD from Dose Escalation Group.
Dose Escalation Group Starting Dose of Cetuximab: 200 mg/m2 initial dose, then 150 mg/m2 by vein over about 1-2 hours on Days 1, 8, 15, and 22 of each 28 day cycle. Dose Expansion Group Starting Dose of Cetuximab: MTD from Dose Escalation Group.
Symptom questionnaire completed at each study visit.
干预措施: Questionnaire (Behavioral)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Treatment with Regorafenib and Cetuximab
时间窗: 4 weeks
MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle (four weeks), determined as the highest dose studied in which the incidence of DLT is less than 33%. DLT defined as any grade 3 or 4 non-hematologic toxicity related to study medication(s) (except nausea and vomiting responsive to appropriate regimens, alopecia, or correctable electrolyte imbalances), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by NCI-CTCAE) despite supportive care; any Grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens; or any severe or life-threatening complication or abnormality not defined in NCI-CTCAE that is attributable to therapy.
次要结局
- Tumor Response of Treatment with Regorafenib and Cetuximab by RECIST Criteria(4 months)
- Tumor Response of Treatment with Regorafenib and Cetuximab by WHO Criteria(4 months)