Phase I Trial of Cetuximab and Erlotinib (EGFR Inhibitors) and SIR-Spheres (Yttrium Microspheres) in Patients With Advanced Malignancies and Liver Metastases
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 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 the combination of selective internal radiation (SIR)-Spheres with yttrium-90 attached and cetuximab. Some participants will also take erlotinib with this combination.
Yttrium-90 microspheres are designed to treat cancer that has spread to the liver. SIR-Spheres are designed to deliver the radiation directly to the liver. This radiation may cause the tumor cells to die.
Cetuximab and erlotinib are drugs that are designed to block the epidermal growth factor receptor (EGFR). EGFR is a protein that helps cancer cells grow. Blocking the EGFR may stop tumors from growing.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, your doctor will decide which group you will be in based on your medical history.
- Group 1 will receive SIR-Spheres with yttrium-90 attached and cetuximab.
- Group 2 will receive SIR-Spheres with yttrium-90 attached, cetuximab, and erlotinib.
Once it is decided which combination you will receive, you will be assigned to a dose level of cetuximab based on when you join the study. Up to 3 dose levels of cetuximab will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable doses of the combinations are found.
All study participants will receive a dose level of the SIR-Spheres with yttrium-90 attached based on the results of the "break-through" scan (described below).
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
- •Patients with advanced or metastatic cancer in the liver, with measureable or evaluable disease, that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months
- •Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment providing radiation is not delivered to the only site of disease being treated under this protocol
- •ECOG performance status </=
- •Patients must have organ and marrow function defined as: • Absolute neutrophil count >/= 500/mL; • Platelets >/=50,000/mL; creatinine </= 2 X ULN; • Total bilirubin </= 2.0; ALT(SGPT) </= 5 X ULN
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence).
- •Patients must be able to understand and be willing to sign a written informed consent document.
排除标准
- •Pregnant or lactating women.
- •Patients who have had hepatic external beam radiotherapy.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres, cetuximab, or erlotinib.
- •Patients with colorectal cancer with known kRAS mutation
- •Hepatic arterial anatomy that would prevent catheterization and the administration of SIR-Spheres into the liver.
- •Greater than 20% arterio-venous shunting of SIR-Spheres to the lungs estimated from a Technetium-99m-macro-aggregated albumin (99mTc-MAA) nuclear medicine break-through scan
- •Contraindication to angiography and selective visceral catheterization: History of severe allergy or intolerance to any contract media, or atropine. Bleeding diathesis, not correctable by usual forms of therapy that would include medical coagulopathy but not limited to the administration of blood products.
- •Utilization of capecitabine for the 6 weeks preceding SIR-Spheres therapy and indefinitely following SIR-Spheres therapy as per manufacturer's recommendations due to the increased risk of radiation hepatitis.
- •Evidence of ascites, biopsy proven cirrhosis, or portal hypertension suggested by the presence of characteristic imaging features on cross-sectional imaging or esophageal varicosities, demonstrated on endoscopy or barium swallow. A diagnostic study to rule out the presence of portal hypertension will not be required unless the findings on cross sectional imaging are suggestive, but not confirmatory.
研究组 & 干预措施
Arm 1 SIR-Spheres + Cetuximab
Arm 1: SIR-Spheres with yttrium-90 attached and cetuximab. SIR-Spheres Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.
干预措施: SIR-Spheres (Device)
Arm 1 SIR-Spheres + Cetuximab
Arm 1: SIR-Spheres with yttrium-90 attached and cetuximab. SIR-Spheres Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.
干预措施: Cetuximab (Drug)
Arm 1 SIR-Spheres + Cetuximab
Arm 1: SIR-Spheres with yttrium-90 attached and cetuximab. SIR-Spheres Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.
干预措施: Break-Through Scan (Procedure)
Arm 2 SIR-Spheres + Cetuximab + Erlotinib.
Arm 2: SIR-Spheres with yttrium-90 attached, cetuximab, and erlotinib. Physicians will assign patients to Arm 1 or Arm 2 based on their discretion. SIR-Spheres on Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Erlotinib start 100 mg by mouth daily starting with Cycle 2. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.
干预措施: SIR-Spheres (Device)
Arm 2 SIR-Spheres + Cetuximab + Erlotinib.
Arm 2: SIR-Spheres with yttrium-90 attached, cetuximab, and erlotinib. Physicians will assign patients to Arm 1 or Arm 2 based on their discretion. SIR-Spheres on Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Erlotinib start 100 mg by mouth daily starting with Cycle 2. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.
干预措施: Cetuximab (Drug)
Arm 2 SIR-Spheres + Cetuximab + Erlotinib.
Arm 2: SIR-Spheres with yttrium-90 attached, cetuximab, and erlotinib. Physicians will assign patients to Arm 1 or Arm 2 based on their discretion. SIR-Spheres on Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Erlotinib start 100 mg by mouth daily starting with Cycle 2. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.
干预措施: Erlotinib (Drug)
Arm 2 SIR-Spheres + Cetuximab + Erlotinib.
Arm 2: SIR-Spheres with yttrium-90 attached, cetuximab, and erlotinib. Physicians will assign patients to Arm 1 or Arm 2 based on their discretion. SIR-Spheres on Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Erlotinib start 100 mg by mouth daily starting with Cycle 2. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.
干预措施: Break-Through Scan (Procedure)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 8 weeks
Maximum tolerated dose (MTD) is defined as the highest dose studied in which the incidence of dose limiting toxicities (DLT) was less than 33% of treated population.
次要结局
未报告次要终点