AT9283 in Children and Adolescents With Relapsed and Refractory Solid Tumors

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor meeting 1 of the following criteria:

  • Refractory to conventional treatment
  • Disease for which no conventional therapy exists
• Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for ≥ 1 week before study entry

PATIENT CHARACTERISTICS:

• WHO performance status (PS) 0-2 OR Lansky Play PS 70-100% (> 50% is acceptable if it is due to a stable neurological deficit or CNS tumor)
• Life expectancy ≥ 12 weeks
• ANC ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Serum bilirubin < 1.5 times upper limit of normal (ULN)
• Creatinine kinase normal
• ALT or AST < 2.5 times ULN (≤ 5 times ULN if due to tumor)
• Creatinine clearance/EDTA-measured GFR ≥ 60 mL/min
• Sufficient blood volume to undergo the blood-sampling regimen specified by the protocol that, in the opinion of the investigator, will not jeopardize patient's safety
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 methods of effective contraception 4 weeks before, during, and for 6 months after completion of study therapy
• Not at high medical risk because of non-malignant systemic disease, including active uncontrolled infection
• Not known to be serologically positive for hepatitis B or C or HIV
• Fractional shortening of > 29% on echocardiogram
• LVEF ≥ 50%
• No history of allergy or auto-immune disease
• No congenital heart disease
• No other condition that, in the investigator's opinion, would not make the patient a good candidate for the clinical trial

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• More than 4 weeks since prior radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, or chemotherapy (6 weeks for investigational medicinal products, 2 weeks for vincristine)
• More than 3 months since prior autologous stem cell transplantation
• No prior allogenic bone marrow transplantation
• No prior extensive radiotherapy to > 25% of bone marrow
• No prior Aurora kinase inhibitor
• No prior major thoracic or abdominal surgery from which the patient has not yet recovered

• No prior or concurrent participation in another interventional clinical trial

  • Participation in an observational study allowed
• No other concurrent anticancer therapy or investigational drugs