Phase 2 single-arm studies of Temozolomide in combination with Topotecan in refractory or relapsing Neuroblastoma and Other pediatric solid tumours. - ITCC 013 - TOTEM2

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 125

Inclusion Criteria

-Histologically or cytologically confirmed neuroblastoma, medulloblastoma, CNS tumor, or other non-CNS solid tumor (at diagnosis)
-Relapsed or refractory tumours 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
-Age at inclusion: 6 months to = 20 years
-Lansky play score ³ 70% or ECOG performance status = 1-Life expectancy ³ 3 months-Adequate organ function:Adequate hematological function: hemoglobin ³ 80 g/L, neutrophil count ³ 1.0 x 109/L, platelet count ³ 100 x 109/L; in case of bone marrow disease: neutrophils ³ 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/L1 – 15 years: = 65 µmol/L15 – 20 years: = 110 µmol/L
Adequate hepatic function: bilirubin £ 1.5 x ULN; AST and ALT £ 2.5 x ULN (AST, ALT = 5 x ULN 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 enrollment 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

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Concurrent administration of any other antitumor 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 Dacarbazin (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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the response rate of Temozolomide in combination with Topotecan in patients with relapsed or refractory neuroblastoma, medulloblastoma or other CNS tumors and to describe response in patients with relapsed or refractory other solid tumors;Secondary Objective: -To determine duration of response, time to progressive disease, time to treatment failure and overall survival<br>-To assess adverse events and toxicity profile of the combination.<br>-To evaluate MGMT expression on archive tumor material by Immuno histochemistry and correlate with response<br>;Primary end point(s): The primary endpoint is the percentage of patients achieving complete or partial response, after having received 2 cycles of Temozolomide - Topotecan (8 weeks)

Secondary Outcome Measures

Name	Time	Method

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