Studies of Temozolomide in Combination With Topotecan in Refractory and Relapsed Paediatric Solid Tumours (TOTEM2)

Inclusion criteria:

• Histologically or cytologically confirmed neuroblastoma, brain tumor or other solid tumor (at diagnosis)
• Relapsed or refractory tumors in which correct standard treatment approaches have failed
• No more than 2 lines of prior chemotherapy
• Measurable primary and/or metastatic disease on CT/MRI at least one bi-dimensionally measurable lesion.

For patients with neuroblastoma, measurable disease will be defined by the modified International Neuroblastoma Staging System (Brodeur et al.1993) completed with MIBG scoring.

• Age at inclusion: 6 months to ≤ 20 years
• Lansky play score ≥ 70% or ECOG performance status ≤ 1
• Life expectancy ≥ 3 months
• Adequate organ function:

Adequate haematological function: haemoglobin ≥ 80 g/l, neutrophil count ≥ 1.0 x 109/L, platelet count ≥ 100 x 109/L; in case of bone marrow disease: neutrophils ≥ 0.5 x 109/l and platelets ≥ 75 x 109/l;

Adequate renal function: normal creatinine related to patient's age:

• 0 - 1 year: ≤ 40 µmol/L
• 1 - 15 years: ≤ 65 µmol/L

• 15 - 20 years: ≤ 110 µmol/L Adequate hepatic function: bilirubin ≤ 1.5 x ULN; AST and ALT ≤ 2.5 x ULN (AST, ALT ≤5xULN in case of liver metastases)

  • Wash-out of 4 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas, 2 weeks in case of vincristine alone; 6 weeks in case of prior radiotherapy (except palliative radiotherapy on non measurable lesions). Patients must have recovered from the acute toxic effects of all prior therapy before enrolment into the study.
  • Patients previously treated with only one of the 2 drugs are eligible.
  • Able to comply with scheduled follow-up and with management of toxicity.
  • All patients with reproductive potential must practice an effective method of birth control while on study. Female patients aged > 12 years must have a negative pregnancy test within 7 days before study treatment.
  • Written informed consent from patient, parents or legal guardian.

Exclusion Criteria:

• Concurrent administration of any other anti-tumour therapy.
• Serious concomitant systemic disorder (for example, active infection including HIV or cardiac disease) that in the opinion of the investigator, would compromise the patient's ability to complete the study.
• History of allergic reaction to the compounds or their solvents.
• History of allergic reaction to Dacarbazine (DITC).
• Galactosemia, Glucose-galactose malabsorption or lactase deficiency.
• Pregnant or breast feeding young women.
• Presence of symptomatic brain metastases in patients with solid non-CNS tumors.