Paclitaxel and CBT-1(Registered Trademark) to Treat Solid Tumors
|ClinicalTrials.gov Identifier: NCT00972205|
Recruitment Status : Completed
First Posted : September 4, 2009
Results First Posted : February 6, 2012
Last Update Posted : July 19, 2012
- 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.
- 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.
-Patients over 18 years of age who have a solid tumor that cannot be treated successfully with standard treatments.
-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.
|Condition or disease||Intervention/treatment||Phase|
|Cervical Ovarian Lung Breast Renal||Drug: paclitaxel Drug: CBT-1(Registered Trademark) Radiation: Tc 99m sestamibi||Not Applicable|
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.
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.
Patients over 18 years of age who have histologic confirmation of relapsed/refractory cancer, following at least once standard treatment regimen, for whom there is no known standard therapy option capable of extending life expectancy. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or better, and have hematologic, renal, hepatic, and metabolic parameters suggestive of adequate organ function.
Patients will be treated according to CBA Research Phase II trial of CBT-1 and Taxol. Patients will begin protocol treatment with orally administered CBT-1(Registered Trademark) in two or three divided doses daily for 7 days. On day 6, 135 mg/m^2 paclitaxel will be administered by intravenous infusion over 3 hours. Prior to the initiation of CBT-1(Registered Trademark), and on Day 6, patients will undergo blood sampling for the rhodamine assay in CD56 plus circulating mononuclear cells. In addition, patients will undergo imaging of tumors and normal tissue with the 99mTc-sestamibi radionuclide scan. These two assays have shown convincing inhibition of Pgp-mediated drug efflux in past studies with Pgp inhibitors such as tariquidar and valspodar. Twelve patients are planned for enrollment to this study, which is powered to determine a difference between the control scan and the post-treatment scan but not to compare CBT-1(Registered Trademark) with previous inhibitors tested in the intramural program.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pharmacodynamic Study of the P-glycoprotein (Pgp) Antagonist, CBT-1(Registered Trademark), Evaluating Pgp Inhibition in Tumors and Normal Tissues|
|Study Start Date :||December 2007|
|Actual Primary Completion Date :||June 2009|
|Actual Study Completion Date :||June 2009|
|Experimental: Paclitaxel and CBT-1||
Paclitaxel 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days.
Drug: CBT-1(Registered Trademark)
CBT-1 500 mg/m^2 oral dose daily for 7 days in divided doses 3 times a day. Cycle days 1-7, repeated every 21 days. no antacids, H2 blocker, or gastric acid inhibiting agents will be administered within 4 hours before or after each daily dose.
Radiation: Tc 99m sestamibi
20 mCI baseline scan day 0; 20 mCI scan on 6th day of CBT-1 administered.
- Percent Increase in Sestamibi Retention in the Liver as a Measure of P-glycoprotein Inhibition [ Time Frame: 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 [ Time Frame: 18 months ]Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
- Percent Inhibition of Rhodamine Efflux From CD56+Cells Post Treatment [ Time Frame: Rhodamine efflux was performed on blood drawn prior to CBT-1 ingestion and after 6 days of dosing. ]Rhodamine 123 was added to whole blood obtained before and after CBT-1. The blood was incubated, layered on lymphocyte separation medium and centrifuged. Peripheral blood mononuclear cells(PBMCs)were isolated, washed and incubated in rhodamine-free medium with or without valspodar. Cells were washed and incubated in phycoerythrin-labeled anti-CD56 antibody or negative control antibody. Rhodamine 123 fluorescence was assessed in CD56+cells with or without valspodar and a 60 min efflux period,continuing the cells without or with valspodar to generate Efflux and PSC/Efflux histograms.
- Number of Participants Who Had an Overall Response [ Time Frame: Baseline to progression ]
Response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Complete response (CR)-disappearance of all target lesions, Partial response (PR)-at least a 30% decrease in the sum of the longest diameter(LD)of target lesions, stable disease (SD) - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
See the Protocol Link module for further details about the RECIST Criteria.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00972205
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Susan S Bates, M.D.||National Cancer Institute, National Institutes of Health|