E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory medulloblastoma and other CNS tumors, neuroblastoma, osteosarcoma and other pediatric miscellaneous solid tumors. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To assess the response rate of gemcitabine in combination with oxaliplatin in patients with relapsed or refractory medulloblastoma and other CNS tumors, neuroblastoma, osteosarcoma and in other pediatric miscellaneous solid tumors. |
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E.2.2 | Secondary objectives of the trial |
- To determine duration of response, time to progressive disease, time to treatment failure and overall survival - To assess adverse events and toxicity profile of the combination - To evaluate the contribution of PET imaging in response assessment in osteosarcoma. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Histologically or cytologically confirmed malignant solid tumor at diagnosis Relapsed or refractory tumors in which correct standard treatment approaches have failed Measurable primary and/or metastatic disease 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 . For patients with osteosarcoma, measurable lesions are lung metastases and osseous lesions with soft tissue tumor, in exclusion of completely calcified or necrosed lesion at study entry. A patient with an unique osseous lesion without soft tissue mass can be included in the study if the lesion is operable and thus accessible for histological response assessment No more than one salvage therapy for relapse Age at inclusion 6 months to 8804; 20 years Lansky play score 61619; 70 or ECOG performance status 8804; 1 Life expectancy 61619; 3 months Adequate organ function Adequate hematological function neutrophil count 61619; 1.0 x 109/L, platelet count 61619; 100 x 109/L; in case of bone marrow disease 61619; 75 x 109/L; hemoglobin 61619; 8 g/dL Adequate renal function creatinine 61603; 1.5 x ULN for age; If serum creatinine is 1.5 ULN of age, then creatinine clearance or radioisotope GFR must be 70 ml/min/1.73 m2 Adequate hepatic function bilirubin 61603; 1.5 x ULN; AST and ALT 61603; 2.5 x ULN AST, ALT 8804;5xULN in case of liver metastases . Wash out of 3 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas, 2 weeks in case of vincristine alone; 4 weeks in case of prior radiotherapy. Patients must have recovered from the acute toxic effects of all prior therapy before enrollment into the study. 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 with childbearing potential must have a negative pregnancy test within 7 days before study treatment. Written informed consent from patient, parents or legal guardian |
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E.4 | Principal exclusion criteria |
Concurrent administration of any other antitumor therapy. Have previously completed or withdrawn from this study or any other study investigating gemcitabine or oxaliplatin. Have a 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 Pre-existing sensory or motor neuropathy Grade 2 excluding neuropathy due to disease and/or surgery History of allergic reaction to platinum compounds Are pregnant or breast feeding Presence of symptomatic brain metastases in patients with solid non-CNS tumors |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for efficacy is the percentage of patients achieving complete or partial response according to WHO guidelines, after having received 4 cycles of gemcitabine-oxaliplatin 8 weeks .Continuing response/stable disease should be confirmed every 4 cycles 2 months until tumor progression or study discontinuation. Safety profile will be evaluated. Clinical and laboratory toxicities/symptomatology will be graded according to NCI-Common toxicity criteria AE v3.0. The adverse events which are not reported in the NCI-Common toxicity criteria will be graded as mild, moderate, severe, life-threatening. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |