Tariquidar and Docetaxel to Treat Patients With Lung, Ovarian, Renal and Cervical Cancer
Condition: Lung Neoplasms; Ovarian Neoplasms; Cervix Neoplasms; Renal Neoplasms
MeSH terms: Neoplasms; Uterine Cervical Neoplasms; Lung Neoplasms; Ovarian Neoplasms; Kidney Neoplasms
Intervention: docetaxel; tariquidar; 99mTc-sestamibi imaging
Intervention description: Patients receive docetaxel intravenous (IV) over 1 hour on days 1 and 8.; Patients receive tariquidar intravenous (IV) over 30 minutes on days 8 and 22.; Bolus injection of 29 mCi of 99mTc-sestamibi intravenously for each imaging study.
Intervention MeSH terms: Docetaxel; Technetium Tc 99m Sestamibi
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pharmacokinetics; Pharmacodynamics; Multidrug Resistance Reversal; Molecular Target; P-Glycoprotein Inhibition; Lung Cancer; Ovarian Cancer; Cervical Cancer; Renal Cancer

Summary:

      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, electrocardiogram (EKG); and possibly
      echocardiogram.

      Participants will undergo the following tests and procedures:

      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 and tariquidar is administered on either day 1 or day 8. The order of
      tariquidar administration is randomized to generate optimal pharmacokinetic data. 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.
    

Eligibility 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 1 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 Interleukin-2 (IL- 2) and deemed to be ineligible; or (c)
             have been evaluated for therapy with IL2 and refused treatment.

          -  Performance status: Eastern Cooperative Oncology Group (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 greater than or equal to 1,500/mL, serum creatine
             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) and serum glutamic oxaloacetic
             transaminase (SGOT) less than or equal to 2.5 x normal limit (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 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 UCN01 treatment.

          -  No serious intercurrent medical illness.

          -  Measurable disease by radiographic means or physical examination. For ovarian cancer,
             assessable disease by cancer antigen 125 (CA125) measurement is allowed.

          -  Willingness to sign a written consent form, and to comply with the protocol.

        Exclusion Criteria:

          -  The following patient populations are not eligible for this 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 this study.

          -  Patients who are poor medical risk because of active, uncontrolled infection or other
             nonmalignant systemic disease.

          -  Human immunodeficiency virus (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 cytochrome P450 3A4
             (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.