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
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...
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.
- INCLUSION CRITERIA:
Patients must fulfill all of the following criteria to be eligible for study admission:
1. Age greater than or equal to 18 years.
2. 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.
3. 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
4. Performance status: ECOG 0-2.
5. Life expectancy of 3 months or greater.
6. 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).
7. 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.
8. No serious intercurrent medical illness.
9. Measurable disease by radiographic means or physical examination. For ovarian
cancer, assessable disease by CA125 measurement is allowed.
10. Willingness to sign a written informed consent form, and to comply with the protocol.
The following patient populations are not eligible for study:
1. 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.
2. The presence of a second malignancy that has not received primary treatment or would
complicate the primary objective of the study.
3. Patients who are poor medical risk because of active, uncontrolled infection or other
non-malignant systemic disease.
4. 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.
5. Patients receiving agents which have major interactions with the CYP3A4 drug
metabolizing system and which cannot be discontinued may not be included in the
6. 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.