E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Neuroblastoma or Miscellaneous Solid Non-CNS Tumors |
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MedDRA Classification |
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 |
The primary objective is to assess the antitumor activity, as measured by objective response rate, of the gemcitabine plus oxaliplatin combination in pediatric patients with neuroblastoma. The antitumor activity of the miscellaneous solid non-CNS tumor cohort will be assessed by describing the responses seen in each tumor type. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are as follows: • to characterize the safety and adverse event profile of the combination (including evaluating adverse events by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE], Version 3) • to assess the following time-to-event endpoints: o duration of response o time to treatment failure o time to progressive disease o overall survival.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients are eligible to be included in the study only if they meet all of the following criteria: [1] Histologically proven malignancy (at diagnosis): either neuroblastoma or other non-CNS solid tumors (excluding osteosarcoma). [2] Measurable primary and/or metastatic disease: For neuroblastoma measurable disease will be defined by the modified International Neuroblastoma Staging System and International Neuroblastoma Response Criteria (Brodeur et al. 1993). For miscellaneous solid non-CNS tumors measurable disease will be defined by RECIST (Therasse et al. 2000). [3] Relapsed or refractory tumors in which standard approaches to treatment have failed. [4] No more than one salvage therapy for relapsed or refractory disease. [5] 6 months to <18 years of age. [6] Lansky play score 70%, or Eastern Cooperative Oncology Group (ECOG) performance status 1 (where more appropriate). [7] Life expectancy 3 months. [8] Adequate organ function including the following:
Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) 1.0 109/L, platelets 100 109/L (in case of bone marrow disease: 75 109/L), and hemoglobin 8.0g/dL.
Hepatic: bilirubin 1.5 times the upper limit of normal ( ULN), aspartate transaminase (AST) and alanine transaminase (ALT) 2.5 ULN (AST, and ALT 5 ULN is acceptable if liver has tumor involvement).
Renal: serum creatinine 1.5 ULN for age, according to local lab value. If serum creatinine >1.5 ULN for age, then creatinine clearance (or radioisotope GFR) must be >70 ml/min/1.73 m2. [9] Must have had their last dose of chemotherapy at least 3 weeks prior to study enrollment (first dose of study treatment); 2 weeks if the prior chemotherapy was single-agent vincristine; 6 weeks if the prior chemotherapy contained nitrosoureas.
Must have had their last dose of radiotherapy at least 4 weeks prior to study enrollment (first dose of study treatment);
Patients must have recovered from the acute toxic effects of all prior therapy before enrollment into the study.
[10] Able to comply with scheduled follow up and with management of toxicity. [11] 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. [12] Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations.
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: [13] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [14] Concurrent administration of any other antitumor therapy. [15] Have previously completed or withdrawn from this study or any other study investigating gemcitabine or oxaliplatin. [16] 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. [17] Have symptomatic brain metastases. [18] re-existing sensory or motor neuropathy >Grade 2 (excluding neuropathy due to disease). [19] History of allergic reaction to platinum compounds. [20] Are pregnant or breastfeeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
objective response rate of the gemcitabine plus oxaliplatin combination in pediatric patients with relapsed or refractory neuroblastoma AND descriptive analysis of responses in the miscellaneous solid non-CNS cohort
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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 | No |
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 | No |
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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |