A Pharmacodynamic Study of the P-glycoprotein (Pgp) Antagonist, CBT-1(Registered Trademark), Evaluating Pgp Inhibition in Tumors and Normal Tissues
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Percent Increase in Sestamibi Retention in the Liver as a Measure of P-glycoprotein Inhibition
研究概览
简要总结
Background:
- Some cancer cells have a large amount of a protein called P-glycoprotein, which can pump certain chemotherapy drugs out of their cells. This pump may be part of the reason why it is difficult to shrink some cancers with chemotherapy.
- In laboratory experiments, the drug CBT-1(Registered Trademark) blocked the P-glycoprotein pump, resulting in accumulation of higher amounts of chemotherapy inside the cancer cells, making the chemotherapy more effective.
- Paclitaxel is a cancer drug that has caused tumors to shrink in many types of cancers, including lung, ovarian, breast, renal, cervical and others.
Objectives:
- To determine whether CBT-1(Registered Trademark) can block the P-glycoprotein pump on cancer cells and whether it inhibits the action of the pump found in normal blood cells and liver tissue.
- To evaluate the effectiveness of combination therapy using CBT-1(Registered Trademark) and paclitaxel in treating solid tumors and to determine whether the two drugs together are more effective than paclitaxel alone.
Eligibility:
-Patients over 18 years of age who have a solid tumor that cannot be treated successfully with standard treatments.
Design:
-Patients receive CBT-1(Registered Trademark) and paclitaxel in 21-day cycles. Treatment continues for two cycles after all the cancer is gone, or until it is decided to surgically remove some or all of the remaining cancer, or until the cancer has grown to the point where it defined as progressive disease.
For each cycle, patients take CBT-1(Registered Trademark) by mouth in three divided doses daily for 7 days. On day 6, paclitaxel is given through a vein over 3 hours.
Blood tests are done before starting CBT-1(Registered Trademark) and repeated periodically throughout treatment.
Imaging studies computed tomography or magnetic resonance imaging (CT or MRI) are done every two cycles. In addition, for the first cycle only, patients undergo imaging of tumors and normal tissue with a 99mTc-sestamibi radionuclide scan before and after administration of CBT-1(Registered Trademark). This scan helps show how well the P-glycoprotein pump is being blocked by the treatment.
详细描述
Background:
This is a pharmacodynamic study aimed at evaluating the efficacy of CBT-1(Registered Trademark) as a modulator of Pgp-mediated drug efflux in patient tumors and normal tissues. The study will build on over a decade of experience with 99mTc-sestamibi imaging and rhodamine accumulation and efflux in normal circulating CD56 plus cells as surrogates for Pgp function. CBA Research, Inc., has carried out Phase I and II testing of CBT-1(Registered Trademark) as a drug resistance reversal agent, but has not yet confirmed that the inhibitor is able to block drug efflux.
Objectives:
Evaluate the impact of CBT-1(Registered Trademark) on the hepatic accumulation and retention of 99mTc-sestamibi in patients with relapsed or refractory solid tumor malignancies.
Evaluate the impact of CBT-1(Registered Trademark) on P-glycoprotein-mediated efflux from CD56 plus peripheral mononuclear cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Paclitaxel and CBT-1
干预措施: paclitaxel (Drug)
Paclitaxel and CBT-1
干预措施: CBT-1(Registered Trademark) (Drug)
Paclitaxel and CBT-1
干预措施: Tc 99m sestamibi (Radiation)
结局指标
主要结局
Percent Increase in Sestamibi Retention in the Liver as a Measure of P-glycoprotein Inhibition
时间窗: sestamibi scanning was performed on day 0 and day 6, allowing scans to be performed pre and post CBT-1 administration
An area under the concentration curve (AUC) was calculated for 99mTc counts over the liver, lungs, and heart. An equation was applied to determine the increase in sestamibi in the liver: \[(AUCpost - AUC baseline)/(AUC baseline)\] x 100.
Number of Participants With Adverse Events
时间窗: 18 months
Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
次要结局
- Percent Inhibition of Rhodamine Efflux From CD56+Cells Post Treatment(Rhodamine efflux was performed on blood drawn prior to CBT-1 ingestion and after 6 days of dosing.)
- Number of Participants Who Had an Overall Response(Baseline to progression)
研究者
Susan Bates
Dr. Susan Bates
National Cancer Institute (NCI)