Paclitaxel and CBT-1(Registered Trademark) to Treat Solid Tumors

NCT00972205 | Completed Results

• 2 other identifiers: 08003508-C-0035
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cervical; Ovarian; Lung; Breast; Renal

Keywords

Pgp; Solid Tumors; Drug Resistance; Sestamibi; Cancer; Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Percent Increase in Sestamibi Retention in the Liver as a Measure of P-glycoprotein Inhibition

  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.

  sestamibi scanning was performed on day 0 and day 6, allowing scans to be performed pre and post CBT-1 administration

• Number of Participants With Adverse Events

  Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

  18 months

Secondary Outcomes (2)

• 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

Study Arms (1)

Paclitaxel and CBT-1

EXPERIMENTAL

Drug: paclitaxel; Drug: CBT-1(Registered Trademark); Radiation: Tc 99m sestamibi

Interventions

paclitaxel DRUG

Paclitaxel 135 mg/m\^2 intravenously on day 6 over 180 minutes. Cycles are repeated every 21 days.

Also known as: Taxol, Onxal

Paclitaxel and CBT-1

CBT-1(Registered Trademark) DRUG

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.

Paclitaxel and CBT-1

Tc 99m sestamibi RADIATION

20 mCI baseline scan day 0; 20 mCI scan on 6th day of CBT-1 administered.

Paclitaxel and CBT-1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must fulfill all of the following criteria to be eligible for study admission:
• Age greater than 18 years.
• Histologic or cytologic confirmation at National Cancer Institute (NCI) Laboratory of Pathology, of recurrent or refractory, or advanced metastatic cancer of the gastrointestinal tract, breast, Taxol (Trademark) naive breast cancer, small cell lung, ovarian, prostate, head and neck, multiple myeloma, non-small cell lung cancer, Taxol (Trademark) naive non-small cell lung cancer.
• Performance status of Eastern Cooperative Oncology Group (ECOG) 0-2.
• Life expectancy of 3 months or greater.
• Patient must have adequate hematologic, renal, hepatic, and metabolic functions as defined: platelet count greater than 100,000 /mL, absolute granulocyte count (AGC) greater than 1500/mL, serum creatinine less than 2.0 mg/dl (or if greater than 2.0, a measured 24 hour creatinine clearance greater than 50 mL/min), serum glutamic oxaloacetic transaminase (SGOT) 4 times institutional upper limit of normal, bilirubin 2.0 mg/dl, prothrombin time (PT) less than 1.5 times institutional upper limit of normal, partial thromboplastin time (PTT) less than 1.5 times institutional upper limit of normal, calcium less than 5.3mEq/L, albumin greater than 2.0 g/dl.
• Electrocardiogram (EKG) showing, at most, minor abnormalities that in the judgment of the protocol chairman would not compromise the patient's ability to tolerate therapy.
• Patients must be greater than 4 weeks from prior radiation or chemotherapy; greater than 2 weeks from hormonal or immunotherapy; greater than 4 weeks from prior experimental therapy; greater than 6 weeks from mitomycin; and greater than 8 weeks from prior UCN01 treatment. Patients receiving dexamethasone as a pretreatment for anaphylactic reactions to Taxol (Trademark) or the cremophor vehicle will not be excluded from this study.
• No serious intercurrent medical illness or serious infection that requires parenteral antibiotics.
• Measurable disease by radiographic means or physical examination.
• Willingness to sign a written informed consent.
• Patients must agree to an effective method of contraception for the study (abstinence, hormonal or barrier method of birth control, or condom) for the study and 30 days after completion of protocol.

You may not qualify if:

• The following patient populations are not eligible for study:
• Women of childbearing potential and potentially fertile men will be excluded unless using an effective contraception (ie. a barrier intrauterine device (IUD), birth control pill, or condom), during the treatment. Women who are pregnant or nursing will also be excluded.
• Patients with significant intercurrent disease.
• Human Immunodeficiencey virus (HIV) seropositive patients. Note: There may be an impact of CBT-1 on the pharmacokinetics of the drugs used in the therapy of HIV.
• Ongoing serious infections that require parenteral antibiotics.
• Patients with significant central nervous system (CNS) disease, including a history of seizures within the last 3 months or psychiatric history which would impair the ability to give informed consent or prevent compliance with protocol requirements.
• Patients must not be eligible for surgery, or radiotherapy that is of known benefit to them, in terms of extension of survival. Patients with tumors sensitive to potentially curative chemotherapy must have failed such chemotherapy. Patients who have received radiation therapy may participate in this study one week after the conclusion of radiation therapy provided that the lesion being irradiated is not one that is being used to assess the efficacy of CBT-1 plus Taxol.
• History of significant coronary artery disease, cardiac arrhythmias requiring treatment, or history of other cardiac disease that in the judgment of the investigators, would compromise the patient's ability to tolerate the therapy.
• Patients with active bleeding due to peptic ulcer disease.
• History of anaphylactic reactions to paclitaxel or cremophor despite adequate premedication.
• Clinically significant bleeding disorders.
• Patients with solid organ allografts.
• Patients on daily gastric acid secretion inhibitors.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Kelly RJ, Robey RW, Chen CC, Draper D, Luchenko V, Barnett D, Oldham RK, Caluag Z, Frye AR, Steinberg SM, Fojo T, Bates SE. A pharmacodynamic study of the P-glycoprotein antagonist CBT-1(R) in combination with paclitaxel in solid tumors. Oncologist. 2012;17(4):512. doi: 10.1634/theoncologist.2012-0080. Epub 2012 Mar 13.

  PMID: 22416063 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page
• Medline Plus
• Drug Information
• US FDA Resources
• RECIST Criteria

MeSH Terms

Conditions

Neoplasms

Interventions

Paclitaxel; Technetium Tc 99m Sestamibi

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Nitriles; Organotechnetium Compounds; Organometallic Compounds

Results Point of Contact

• Title: Susan S. Bates, M.D.
• Organization: National Cancer Institute (NCI), National Institutes of Health (NIH)

Batess@mail.nih.gov

301-402-0984

Study Officials

• Susan S Bates, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Susan Bates

Study Record Dates

• First Submitted: September 3, 2009
• First Posted: September 4, 2009
• Study Start: December 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: July 19, 2012
• Results First Posted: February 6, 2012

Record last verified: 2012-07

Locations

US (1)