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P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors Clinical Trials Data presented on Clinical Trials Search isn't meant to be a substitute for qualified health advice, calls or treatment using a genuine doctor. We are not docs. Always consult your dr. on P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors conditions. Clinical Trials Search.org is a site dedicated to listing clinical research studies in human subjects. P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors Clinical research trials and P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors healthcare trials occur in a lot of of places throughout the United States. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials generally assess the potency of new drugs. The intent of the studies / undertakings is to figure out certain human medical questions. Clinical trials are a popular means for mDs, government agencies, and private sector corporations to locate remedies for all kinds of circumstances, including P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors. P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors Clinical Trials and other clinical trials allow volunteers to obtain health treatment alternatives before they are available to the masses. Many times the participants undergo treatment for free, and sometimes they are paid for their time. Occasionally there is a cost for a P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors clinical trial. Participants typically obtain the most effective healthcare available for their P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors condition. Dangers are a reality, nonetheless, and can include extra or frequent mD trips, medical hazards (potentially life-endangering), and/or the treatment being uneffective. Trials are federally regulated with rigid guidelines to protect clinical trials patients.
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Home > "P" Clinical Trials Conditions > P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors  P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors
P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors
For Condition: Ewing's Sarcoma,Brain Tumor,Rhabdomyosarcoma,Neuroblastoma
Status: Recruiting
Sponsor(s): National Cancer Institute (NCI) ,
Synopsis: This study will examine the safety and side effects of tariquidar in children and adolescents with cancer and test whether it can improve current anticancer drug treatments. Tumor resistance to chemotherapy is a major problem in cancer treatment. Studies have found that a protein (P-glycoprotein) on some cancer cells pumps anticancer drugs out of the cells, reducing treatment effectiveness. In laboratory tests, an experimental drug called tariquidar has blocked pumping by this protein. It is being used in this study to try to increase amounts of the anticancer drugs vinorelbine (Navelbinea), doxorubicin (Adriamycin) or docetaxel (Taxotere) in cancer cells. Patients between 2 and 18 years of age with solid tumors-including rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, liver tumors, germ cell tumors, and primary brain tumors-who have relapsed or who do not respond to frontline therapy and have no other treatment options may be eligible for this study. Candidates will be screened with a medical history, physical and neurological examinations, blood and urine tests, electrocardiogram, MUGA (nuclear medicine scan of the heart) and radiologic studies to evaluate the extent of disease. Participants will receive tariquidar plus either doxorubicin, vinorelbine or docetaxel, depending on the type of cancer, previous treatments, and side effects of prior treatment. Patients taking doxorubicin will also receive GCSF, a drug that helps boost the immune system, and dexrazoxane, a medicine to lessen the harmful effects of doxorubicin on the heart. Patients taking docetaxel will also receive GCSF, plus medicines to prevent an allergic reaction to the docetaxel. Treatment will be given in 21-day cycles for no more than eight cycles. The first treatment cycle for each regimen begins with a baseline Sestamibi scan-an imaging procedure that uses the radioactive drug Tc-99m Sestamibi. This drug accumulates in tumor cells and is eliminated from them in much the same way that some cancer drugs are eliminated from cells. The drug is injected into a vein and a series of pictures taken with a camera that detects radioactivity shows where the radioactive Sestamibi distributes in the body, including in the cancer, liver and heart. This procedure can monitor for effects of tariquidar on resistance to therapy. The day after the Sestamibi scan, tariquidar is given intravenously (through a vein), followed by another Sestamibi scan. On the third day, tariquidar is given, followed by the treatment drug (doxorubicin, vinorelbine or docetaxel). Patients taking vinorelbine will repeat the tariquidar and vinorelbine doses 1 week after the first. Sestamibi scans are done during the first treatment cycle only for each drug regimen. In addition, for the first treatment cycle only, 17 blood samples of less than one-half teaspoon each are drawn to study the pharmacology of tariquidar (i.e., how the drug works in the body), and another 17 samples are taken to study the pharmacology of the chemotherapy drug. A device, such as a heparin lock, is put in place to avoid having multiple needlesticks for these blood draws. Routine blood tests are done twice a week and various tests, such as X-rays, CT and MRI scans are done periodically to follow the progress of the cancer throughout the treatment period. Patients taking doxorubicin will also have an echocardiogram or MUGA to evaluate heart function. Patients are examined by a doctor at least once a week.
Details: Pgp is a 170 kDa plasma membrane glycoprotein that functions as a non-specific energy-dependent drug efflux pump. Pgp is expressed in a variety of normal human tissues, such as renal proximal tubules, capillary endothelial cells that comprise the blood-brain barrier, epithelial cells lining the bile canaliculi, bone marrow stem cells, and peripheral blood mononuclear cells. Pgp over-expression in tumor cells results in a multidrug resistance phenotype by preventing the intracellular accumulation of a variety of chemotherapeutic agents, including anthracyclines, taxanes, vinca alkaloids, and epipodophyllotoxins. Inhibition of Pgp may partially reverse multidrug resistance by increasing intracellular drug accumulation in tumor cells. Non-specific Pgp reversal agents, such as cyclosporine and verapamil, have limited clinical efficacy, because of unacceptable side effects at doses that were suboptimal for maximum Pgp inhibition and because they substantially altered the pharmacokinetics of anticancer drugs that are Pgp substrates. Tariquidar (XR9576) is a specific Pgp inhibitor that blocks Pgp function for up to 24 hours after a single dose without significant toxicity in animals and humans. In adults tariquidar in combination with doxorubicin, paclitaxel, or vinorelbine is well tolerated, and only minor alterations in the clearance and drug exposure (area under the concentration time curve, AUC) of the anticancer drugs have been observed. A phase I trial and pharmacokinetic study of intravenous tariquidar in children with refractory solid tumors including brain tumors will be conducted. Tariquidar will be administered in combination with doxorubicin, vinorelbine, or docetaxel. The spectrum of toxicity at three dose levels of tariquidar will be defined in pediatric patients and alterations in the pharmacokinetics and toxicity of doxorubicin, vinorelbine or docetaxel will be monitored. Additionally, we will evaluate the pharmacodynamics of tariquidar ex vivo using rhodamine assay in peripheral blood mononuclear cells and in vivo using functional imaging with 99mTc sestamibi.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA: Age: Patients must be greater than or equal to 2 and less than or equal to 18 years of age. Diagnosis: Histologically confirmed solid tumors which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors, and primary brain tumors. In patients with brain stem or optic gliomas the requirement for histological confirmation may be waived. Measurable/Evaluable Disease: Patients must have measurable or evaluable tumors. Prior Therapy: The patient's cancer must have relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities. Patients must have had their last dose of radiation therapy at least four weeks prior to study entry, their last dose of chemotherapy at least 21 days prior to study entry (28 days for nitrosoureas), and their last dose of any investigational cancer therapy at least 30 days prior to study entry. Patients must have recovered from the toxic effects of all prior therapy before entry onto this trial. Patients with brain tumors must be on a stable or tapering dose of corticosteriods for 7 days prior to the baseline scan performed for the purpose of assessing response to therapy on this study. Patients should be off colony stimulating factors such as G-CSF, GM-CSF, erythropoietin, and IL-11 for at least 72 hours prior to study entry. Lifetime cumulative dose of anthracycline: Restrictions on the prior cumulative dose anthracylines only apply to patients who will receive doxorubicin in combination with tariquidar. The lifetime cumulative dose of anthracycline must be less than or equal to 300 mg/m(2) in patients who will receive doxorubicin in combination with tariquidar, if the anthracycline was administered as a bolus injection without a cardioprotectant (e.g., dexrazoxane) OR if the patient had mediastinal radiation. The lifetime cumulative dose of anthracycline must be less than or equal to 400 mg/m(2), if the anthracycline was administered by continuous infusion or with a cardioprotectant and the patient has not had mediastinal radiation. Performance Status: Patients should have an ECOG performance status of 0,1, or 2. Patients who unable to walk because of paralysis or weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score. Hematologic Function: Patients must have adequate bone marrow function, defined as a peripheral absolute granulocyte count of greater than or equal to 1,500/microL, hemoglobin greater than or equal to 8 gm/dL, and a platelet count greater than or equal to 100,000/microL. Hepatic Function: Patients must have adequate liver function, defined as bilirubin within normal limits, SGPT (ALT) less than 2x the upper limit of normal. Renal Function: Patients must have an age-adjusted normal serum creatinine OR a creatinine clearance greater than or equal to 60 mL/min/1.73 m(2). Cardiac Function: Patients who will receive doxorubicin must have normal cardiac ejection fraction by echocardiogram. An echocardiogram does not need to be performed in patients who will receive docetaxel or vinorelbine. Informed Consent: All patients or their legal guardians (if the patient is less than 18 years old) must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed. (This does not include routine laboratory tests or imaging studies required to establish eligibility). Durable Power of Attorney (DPA): Patients who have brain tumors and who are greater than or equal to 18 years of age will be offered the opportunity to assign a DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired. EXCLUSION CRITERIA: Clinically significant unrelated systemic illness, such as serious infections, hepatic, renal or other organ dysfunction, which in the judgement of the Principle or Associate Investigator would compromise the patient's ability to tolerate and of the agents in this trial or are likely to interfere with the study procedures or results. Patients with a history of bone marrow transplantation within the previous 4 months or extensive radiotherapy (craniospinal radiation, total body radiation, or radiation to more than half of the pelvis) within the previous 4 months. Pregnant or breast feeding females are excluded because tariquidar in combination with a cytotoxic drug may be harmful to the developing fetus or nursing child.
Total Enrollment: 36
Location and Contact Information:
National Cancer Institute (NCI) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 010091; 01-C-0091
Study Start Date: February 15, 2001
Record last reviewed: February 1, 2004
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00011414
Other Rhabdomyosarcoma Studies:
1. Temozolomide and O6-Benzylguanine for Treating Childhood Cancers
2. Comparison of Filgrastim and Filgrastim SD/01in Boosting White Cell Counts after Intensive Chemotherapy
3. A Pilot Study of Tumor-Specific Peptide Vaccination and IL-2 with or without Autologous T Cell Transplantation in Recurrent Pediatric Sarcomas
4. Phase I Trial and Pharmacokinetic Study of TLC D-99 in Pediatric Patients with Refractory Solid Tumors
5. A Pilot Study of Autologous T-Cell Transplantation with Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas
Related Studies:
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Other Maryland Clinical Trials
Other Bethesda Clinical Trials
P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors
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