Protocol Number: 01-C-0091

Title:

Phase I Trial and Pharmacokinetic Study of Tariquidar (XR9576), a P-Glycoprotein Inhibitor, in Combination with Doxorubicin, Vinorelbine or Docetaxel in Pediatric Patients with Refractory Solid Tumors Including Brain Tumors

Number:

01-C-0091

Summary:

This study will evaluate the tolerance and effects of tariquidar, given in combination with one of three anticancer drugs, for treating solid tumors. Tariquidar works by blocking a pump on a cancer cell. The pump on a cell that prevents anticancer drugs from accumulating is called Pgp (P-glycoprotein). Researchers hope to see whether cancer-fighting drugs can stay in the cells longer.

Patients ages 2 to 18 who have solid tumors may be eligible for this study. Tariquidar is infused intravenously (IV) over 30 minutes, given every 21 to 28 days, with one drug that kills cancer cells. Patients are examined by a doctor at least once weekly during treatment and will have routine blood tests twice weekly. They will receive one of the following drugs with tariquidar: doxorubicin (Adriamycin™ (Trademark)), vinorelbine (Navelbine™ (Trademark)), or docetaxel (Taxotere™ (Trademark)). At the first treatment cycle only, there is a baseline Sestamibi scan before treatment and a second one immediately after drug administration. If patients receive tariquidar with doxorubicin, tariquidar is given alone. Then 48 to 72 hours later, the second dose is given, followed by doxorubicin by IV over 15 minutes. Dexrazoxane, which decreases damaging effects of doxorubicin on the heart, is also given by IV over 15 minutes. Granulocyte colony stimulating factor (G-CSF) is injected daily 48 hours after doxorubicin, to alleviate doxorubicin's effect on white blood cells. If patients receive tariquidar with vinorelbine, tariquidar is given alone. Then 48 to 72 hours later, the second dose is given, immediately followed by vinorelbine by IV over 10 minutes; then 1 week later, tariquidar is again given, immediately followed by vinorelbine by IV for 10 minutes. G-CSF is given daily. If patients receive tariquidar with docetaxel, tariquidar is given alone. Then 48 to 72 hours later, the second dose is given, followed by docetaxel by IV over 60 minutes. Drugs to prevent allergic reactions are given before and after each docetaxel dose. G-CSF is given daily.

Tariquidar may affect blood pressure during infusion, and there can be reduction of normal blood cells, gastrointestinal problems, and allergic reactions. The radioactive Sestamibi can cause headache, chest pain, and nausea. Radiation used in this study has been approved as involving a slightly greater than minimal risk for adults and an acceptable risk for children. This radiation is considered necessary to obtain information desired. One possible effect is a slight increase in the risk of cancer.

This study may or may not have a direct benefit for participants. However, knowledge gained may benefit people with cancer in the future.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Multidrug Resistance

Childhood Cancer

SESTAMIBI

Rhodamine

Drug Interaction

Recruitment Keyword(s):

Childhood Cancer

Brain Tumor

Drug Resistance

Chemotherapy

Condition(s):

Brain Tumor

Ewing's Sarcoma

Neuroblastoma

Rhabdomyosarcoma

Investigational Drug(s):

Tariquidar (XR9576)

Investigational Device(s):

None

Interventions:

Drug: Tariquidar (XR9576)

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Clinical significance of P-glycoprotein in multidrug resistance malignancies

Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance

P-glycoprotein and multidrug resistance in cancer chemotherapy

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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