RATIONALE: Drugs used in chemotherapy, such as docetaxel, doxorubicin, and vinorelbine, work in different ways to stop tumor cells from dividing so they stop growing or die. Tariquidar may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drug.

PURPOSE: This phase I trial is studying the effectiveness of tariquidar plus chemotherapy in treating children who have relapsed or refractory solid tumors.

OBJECTIVES:

• Determine the toxic effects and tolerability of tariquidar combined with docetaxel, doxorubicin, or vinorelbine in children with relapsed or refractory solid tumors.
• Determine the maximum tolerated dose of tariquidar in this patient population.
• Determine the pharmacokinetics of tariquidar alone and in combination with docetaxel, doxorubicin, or vinorelbine in this patient population.

OUTLINE: This is a dose-escalation study of tariquidar.

Patients receive tariquidar IV over 30 minutes on days -1 and 1 of course 1 and on day 1 of all subsequent courses. Patients also receive one of the following: doxorubicin IV over 15 minutes on day 1; vinorelbine IV over 10 minutes on days 1 and 8; or docetaxel IV over 60 minutes on day 1. Patients receiving doxorubicin or docetaxel also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 3 and continuing until blood counts recover. Patients receiving vinorelbine also receive G-CSF SC beginning on day 10 and continuing until blood counts recover. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tariquidar until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. An additional 18 patients (at least 3 under age 12 and at least 3 who are age 12 and older) are treated at the MTD. Intrapatient dose escalation may take place for patients in cohorts 1 and 2 after 2 courses of treatment.

Patients undergo blood collection periodically for pharmacokinetic and pharmacodynamic studies.

Patients are followed every 6 weeks for 1 year and then every 12 weeks during study treatment.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

• Brain and Central Nervous System Tumors
• Childhood Germ Cell Tumor
• Extragonadal Germ Cell Tumor
• Kidney Cancer
• Liver Cancer
• Neuroblastoma
• Ovarian Cancer
• Sarcoma
• Unspecified Childhood Solid Tumor, Protocol Specific

• Biological: filgrastim
• Drug: docetaxel
• Drug: doxorubicin hydrochloride
• Drug: tariquidar
• Drug: vinorelbine ditartrate
• Other: pharmacological study

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor, including, but not limited to the following tumor types:

  • Rhabdomyosarcoma and other soft tissue sarcomas
  • Ewing's sarcoma family of tumors
  • Osteosarcoma
  • Neuroblastoma
  • Wilm's tumor
  • Hepatic tumors
  • Germ cell tumors
  • Primary brain tumors (histological confirmation may be waived for brain stem or optic gliomas)
• Relapsed or refractory disease after prior front-line therapy
• No other potentially curative therapy exists
• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

• 2 to 18

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Hemoglobin at least 8 g/dL
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal
• SGPT less than 2 times upper limit of normal
• No hepatic dysfunction that would preclude study therapy

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min
• No renal dysfunction that would preclude study therapy

Cardiovascular:

• Normal cardiac ejection fraction by echocardiogram if receiving doxorubicin on study

Other:

• No serious systemic infection that would preclude study participation
• No other significant systemic illness that would preclude study participation
• No other organ dysfunction that would preclude study therapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 72 hours since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], epoetin alfa, or interleukin-11)
• More than 4 months since prior bone marrow transplantation
• No concurrent immunotherapy

Chemotherapy:

• All patients:

  • At least 21 days since prior chemotherapy (28 days for nitrosoureas)
  • No other concurrent chemotherapy

• Patients receiving doxorubicin on study must meet 1 of the following criteria:

  • No more than 300 mg/m^2 prior cumulative dose of anthracycline if administered as a bolus injection without cardioprotectant (e.g., dexrazoxane) OR if mediastinal radiotherapy was received
  • No more than 400 mg/m^2 prior cumulative dose of anthracycline if administered as a continuous infusion or with cardioprotectant AND no mediastinal radiotherapy was received

Endocrine therapy:

• Concurrent corticosteroids allowed for brain tumors if dose is stable or tapering for at least 7 days prior to study entry

Radiotherapy:

• See Chemotherapy
• At least 4 weeks since prior radiotherapy for patients receiving doxorubicin
• At least 4 weeks since prior craniospinal radiotherapy, total body radiotherapy, or radiotherapy to more than half of the pelvis for patients receiving docetaxel or vinorelbine
• At least 2 weeks since prior limited-field radiotherapy (local) for patients receiving docetaxel or vinorelbine
• No concurrent radiotherapy

Other:

• Recovered from all prior therapy
• At least 30 days since prior investigational cancer therapy
• No other concurrent investigational agents