Paclitaxel and CBT-1(Registered Trademark) to Treat Solid Tumors
Condition: Cervical; Ovarian; Lung; Breast; Renal
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.

      Eligibility:

      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.

      Design:

      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.
    

Intervention name(s): paclitaxel; CBT-1(Registered Trademark); Tc 99m sestamibi
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): Paclitaxel 135 mg/m^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days.; 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.; 20 mCI baseline scan day 0; 20 mCI scan on 6th day of CBT-1 administered.
Other intervention name(s): Taxol; Onxal
Intervention MeSH terms: Paclitaxel; Technetium Tc 99m Sestamibi
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pgp; Solid Tumors; Drug Resistance; Sestamibi; Cancer; Solid Tumor