Dettagli per singolo studio

DEC-NET Serial number FR380

Published online	01/04/2005 14.22.00
Last updated	09/09/2005 15.57.54

Other protocol ID number
Current trial status	Complete(closed to recruitment of participants: follow-up complete)
Major Disease (ICD9 class)	MALIGNANT NEOPLASM OF ADRENAL GLAND
Experimental drug
Temozolomide Treatment regimen (dosage and duration) Children on study will receive oral temozolomide 200 mg/m2 once daily for 5 consecutive days, in each 28 day cycle. Patients who have received a stem cell transplant, or in whom there is bone marrow involvement, will receive a reduced dose of 150 mg/m2/day for 5 days in the first cycle.
Gender	Both
Age (range)	> 12 months et < 20 years
Eligibility criteria
Inclusion criteria
1/Patient: -Age at inclusion in trial > 1 year and < 16 years -Lansky score > 30 (Appendix 5) -Life expectancy > 2 months -Organ toxicity < Grade 2 (according to NCI-CTC version 2: Appendix 5) -Platelets > 100 x 109/L (or > 50 x 109/L after stem cell transplant or if there is marrow involvement) -Neutrophil count > 0.5x 109/L -Bilirubin < 1.5 x normal -AST (SGOT) and ALT (SGPT)< 2.5 x normal -Informed, written consent obtained from parent, guardian and/or patient as appropriate -National and Local Ethical Committee approval for protocol 2/Disease: -Histologically proven neuroblastoma -High risk relapsed or refractory disease ie metastatic neuroblastoma or localised MYC-N amplifed neuroblastoma or 2nd relapse of localised non MYC-N amplified neuroblastoma(MYC-N status should have been determined on a sample sent to one of the National Reference Laboratories). -Measurable primary or metastatic disease on cross-sectional imaging or MIBG 3/Treatment: -Last chemotherapy treatment > 21 days preceding the start of temozolomide (13-cis retinoic acid is counted as chemotherapy for this purpose) -Last radiotherapy treatment (if given) > 30 days preceding the start of temozolomide (local palliative treatment for the purpose of pain control is allowed within 30 days). -Child has received no more than 2 previous strategies of treatment for neuroblastoma. Inclusion criteria to be met within 14 days preceding the start of treatment.
Exclusion criteria
-Failure to meet inclusion criteria -Known HIV positive patient (testing only required prior to study entry if high index of suspicion). -Pregnant or lactating females -Any other invalidating pathology -Other concomitant investigative treatment for neuroblastoma
Trial design/methodology
Phase	2
Kind of study	Efficacy Safety
Design
Purpose of study
1/ Primary: -To determine the anti-tumour activity of temozolomide in high risk relapsed or refractory neuroblastoma 2/ Secondary: -To determine the duration of response to temozolomide -To evaluate the tolerability of the drug in this patient population -To evaluate the tumoural expression of the cellular repair mechanisms which repair DNA damage induced by temozolomide (MGMT and mismatch repair (MMR) systems) and to correlate with outcome of temozolomide treatment. -To show whether MGMT and MMR expression/activity changes in tumour between initial presentation and relapse/progression and following temozolomide treatment. -To quantify the activity of MGMT in bone marrow taken at relapse and correlate with haematological toxicity.




Summary of study design, objectives, and ongoing research findings
Children with high risk relapsed or refractory neuroblastoma receive oral temozolomide daily for 5 days per 28 day cycle. After two courses of temozolomide, response to treatment will be assessed. The main aim of this study is to determine the response rate to temozolomide after 2 courses of treatment. Secondary aims are to evaluate duration of response, the tolerability of the drug in this population, to determine the phenotype of tumour resistance to temozolomide and to relate O6alkyl-guanine transferase (Alk-transferase or MGMT) activity in bone marrow to haematological toxicity. Phase II trial, determining the antitumor efficacy of temozolomide in high risk relapsed or refractory neuroblastoma in patients of more than 1 year. The temozolide is managed by oral way with the amount of 200 mg/m2/j during 5 days consecutive every 28 days. The effectiveness and the toxicity of the treatment are evaluated after 2 cures.