Tariquidar and Docetaxel to Treat Patients With Lung, Ovarian, Renal and Cervical Cancer - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00069160

Purpose

The purpose of this study is three-fold: 1) to examine the ability of the experimental drug tariquidar to improve chemotherapy results by blocking a protein (P-glycoprotein) on some cancer cells that acts to pump out cancer drugs; 2) examine how tariquidar interacts with the cancer drug docetaxel; and 3) evaluate the effectiveness of combination treatment with tariquidar and docetaxel in treating patients with lung, ovarian, or cervical cancer.

Patients 18 years of age and older with recurrent or metastatic (spreading) lung, cervical, or ovarian cancer who cannot benefit from any standard treatment may be eligible for this study. Candidates will be screened with a medical history and physical examination; review of pathology slides; blood and urine tests; imaging tests, including computed tomography (CT) or magnetic resonance imaging (MRI) scans; chest x-ray, and possibly a bone scan or other imaging tests needed to evaluate the cancer; electrocardiogram (EKG); and possibly echocardiogram.

Participants will undergo the following tests and procedures:

Tumor biopsy. Before starting chemotherapy, a small piece of tumor is removed to study the P-glycoprotein pump and to determine the tumor genetics.
Blood draw. Blood is drawn before treatment begins to establish baseline levels for future blood tests. Blood counts are done twice weekly after chemotherapy begins.
Central venous catheter placement. A plastic tube is put into a major vein in the chest. It is used to give the study drugs or other medications, including antibiotics and blood transfusions, if needed, and to withdraw blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room. It can stay in the body for months or be removed after each treatment is completed.
Chemotherapy. Treatment cycles are 21 days. Both drugs are given on day 1 of each cycle. First, tariquidar is given as a 30-minute infusion. One hour after the tariquidar infusion, docetaxel is infused over 1 hour. (For the first cycle only, docetaxel is given in divided doses one week apart. Patients will be hospitalized for several days during this cycle to gather research data.) The tariquidar dose remains the same throughout the study. Docetaxel may be increased or decreased from cycle to cycle, based on side effects. Treatment will continue for two cycles after all the cancer is gone, or until surgery is done to remove some or all of the remai...

Condition	Intervention	Phase
Lung Neoplasms Ovarian Neoplasms Cervix Neoplasms Renal Neoplasms	Drug: docetaxel Drug: tariquidar	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	A Clinical Trial of the P-Glycoprotein Antagonist, Tariquidar (XR9576), in Combination With Docetaxel in Patients With Lung, Ovarian, Renal and Cervical Cancer: Analysis of the Interaction Between Tariquidar and Docetaxel

Resource links provided by NLM:

MedlinePlus related topics: Cancer Cervical Cancer Kidney Cancer Lung Cancer Ovarian Cancer

Drug Information available for: Docetaxel Tariquidar

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Pharmacokinetics [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Clinical response [ Designated as safety issue: No ]
Impact of tariquidar on technietium Tc 99m sestamibi uptake [ Designated as safety issue: No ]

Enrollment:	48
Study Start Date:	September 2003
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I (course I) Patients receive docetaxel IV over 1 hour on days 1 and 8 and tariquidar IV over 30 minutes on days 8 and 22.	Drug: docetaxel Given IV Drug: tariquidar Given IV
Experimental: Arm II (course 1) Patients receive docetaxel IV over 1 hour on days 1 and 8 and tariquidar IV over 30 minutes on days 1 and 22.	Drug: docetaxel Given IV Drug: tariquidar Given IV

Detailed Description:

Intrinsic and acquired drug resistance remain major obstacles in the treatment of cancer. Accumulating evidence indicates that in some malignancies Pglycoprotein (Pgp) can confer resistance, and that its reversal can improve therapeutic outcome. Clinical trials investigating Pgp antagonists have been hampered by the occurrence of unpredictable pharmacokinetic interactions, which have required dose reductions of the chemotherapeutic agents to avert excessive toxicity. Tariquidar (XR9576) is a new Pgp antagonist that is more potent and has prolonged activity. Phase I trials with paclitaxel, vinorelbine, and doxorubicin have demonstrated that tariquidar (XR9576) has minimal pharmacokinetic interactions while surrogate studies have confirmed in vivo inhibition of Pgp-mediated drug transport. This study seeks to determine the pharmacokinetic interaction, if any, between docetaxel and tariquidar and to evaluate the potential for activity in lung, ovarian, primary peritoneal, fallopian tube and cervical cancers. Renal cell cancer has been added in a 3/1/06 amendment. The secondary goal is to evaluate the impact of tariquidar on uptake of (99m)Tc-sestamibi in recurrent or metastatic tumors of patients with lung, ovarian, renal or cervical cancer.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

Patients must fulfill all of the following criteria to be eligible for study admission:

Age greater than or equal to 18 years.
Histologic or cytologic confirmation of lung, cervical, or ovarian cancer, following at least one standard treatment regimen, and for which there is no known standard therapy capable of extending life expectancy. Female patients with primary papillary carcinoma of the peritoneum and fallopian tube cancers will be included in the latter group, as the disease entities are closely associated with epithelial ovarian carcinoma, can be difficult to distinguish, have a similar epithelial origin, and are treated in an identical manner.
Histologic or cytologic confirmation of renal cell carcinoma

(clear cell, type I and type II papillary chromophobe, collecting duct and medullary). Patients should have received either sunitinib or sorafenib, unless deemed ineligible for treatment with either agent. In addition, patient should either: (a) have received IL-2; (b) have been evaluated for therapy with IL-2 and deemed to be ineligible; or (c) have been evaluated for therapy with IL-2 and refused treatment.
Performance status: ECOG 0-2.
Life expectancy of 3 months or greater.
Suitable candidate for receiving planned therapy as evidenced by screening laboratory assessments hematologic, renal, hepatic, and metabolic functions: platelet count greater than or equal to 90,000/mL absolute granulocyte count (AGC) greater than or equal to 1,500/mL, serum creatinine less than or equal to 1.5 mg/dl (or if greater than 1.5, a measured 24 hour creatinine clearance greater than or equal to 50 mL/min), SGPT and SGOT less than or equal to 2.5 x NL, and bilirubin less than or equal to 1.5 x NL (in patients with clinical evidence of Gilbert's disease, less than or equal to 3 x NL).
Patients must be greater than or equal to 4 weeks from prior radiation or chemotherapy; greater than 2 weeks from hormonal therapy; greater than 4 weeks from prior experimental therapy; greater than 6 weeks from mitomycin C; and greater than 8 weeks from prior UCNO1 treatment.
No serious intercurrent medical illness.
Measurable disease by radiographic means or physical examination. For ovarian cancer, assessable disease by CA125 measurement is allowed.
Willingness to sign a written informed consent form, and to comply with the protocol.

EXCLUSION CRITERIA:

The following patient populations are not eligible for study:

Pregnant or nursing women are not eligible; women of childbearing age must agree to use an effective method of contraception. Pregnant women are not eligible because of teratogenic effects of chemotherapy.
The presence of a second malignancy that has not received primary treatment or would complicate the primary objective of the study.
Patients who are poor medical risk because of active, uncontrolled infection or other non-malignant systemic disease.
HIV seropositive patients. Patients infected with the HIV virus will be excluded from this trial because the effect of the combination of tariquidar and docetaxel on HIV replication and/or the immune system is unknown and potentially harmful.
Patients receiving agents which have major interactions with the CYP3A4 drug metabolizing system and which cannot be discontinued may not be included in the trial.
Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00069160

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Ling V, Thompson LH. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol. 1974 Feb;83(1):103-16. No abstract available.

Akiyama S, Fojo A, Hanover JA, Pastan I, Gottesman MM. Isolation and genetic characterization of human KB cell lines resistant to multiple drugs. Somat Cell Mol Genet. 1985 Mar;11(2):117-26.

Beck WT, Cirtain MC, Lefko JL. Energy-dependent reduced drug binding as a mechanism of Vinca alkaloid resistance in human leukemic lymphoblasts. Mol Pharmacol. 1983 Nov;24(3):485-92.

Responsible Party:	Susan E. Bates, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00069160 History of Changes
Obsolete Identifiers:	NCT00072202
Other Study ID Numbers:	030284, 03-C-0284
Study First Received:	September 15, 2003
Last Updated:	January 11, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Pharmacokinetics
Pharmacodynamics
Multidrug Resistance Reversal
Molecular Target
P-Glycoprotein Inhibition

Lung Cancer
Ovarian Cancer
Cervical Cancer
Renal Cancer

Additional relevant MeSH terms:

Neoplasms
Uterine Cervical Neoplasms
Kidney Neoplasms
Lung Neoplasms
Ovarian Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Urologic Neoplasms
Kidney Diseases

Urologic Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Endocrine System Diseases
Gonadal Disorders
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012