refractory or relapsing malignant pediatric solid tumors
Conditions
Interventions
Trade Name: Gemzar 200 mg
Product Name: Gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Gemcitabine
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Institut Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
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 = 20 years • Lansky play score ³ 70% or ECOG performance status = 1 • Life expectancy ³ 3 months• Adequate organ function:Adequate hematological function: neutrophil count ³ 1.0 x 109/L, platelet count ³ 100 x 109/L; in case of bone marrow disease: ³ 75 x 109/L; hemoglobin ³ 8 g/dLAdequate renal function: creatinine £ 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 m2Adequate hepatic function: bilirubin £ 1.5 x ULN; ASAT and ALAT £ 2.5 x ULN (ASAT, ALAT =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 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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.;Primary end point(s): >Efficacy: - CNS tumors (medulloblastoma and other CNS tumors): MRI. Optional: functional MRI, Thallium scintigraphy and Methionin PET. - Neuroblastoma: CT, MRI, MIBG scan. Recommended: bone marrow aspiration and biopsies. - Osteosarcoma: CT, MRI, technetium scintigraphy.PET imaging(CT PET preferably) is highly recommended to study its contribution in tumor response assessment. Histology is mandatory for patients with non measurable unique osseous lesion and is highly recommended for other patients. - Miscellaneous solid non-CNS tumors: CT, MRI. Optional: Scintigraphy, Bone Marrow aspirates and biopsies 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). Any CR and PR should be confirmed not less than 4 weeks later, except when an early surgery is performed or a second-line treatment is administered before confirmation at 4 weeks.For neuroblastoma patients, tumor response will be assessed using the modified International Neuroblastoma Response Criteria (Brodeur et al. 1993). Efficacy will be assessed separately in each of the cohorts. An external response review committee will review all the observations to validate responses and failures. Continuing response/stable disease should be confirmed every 4 cycles (2 months) until tumor progression or study discontinuation. Furthe | — |
Countries
Germany, Italy, Netherlands, United Kingdom
Outcome results
None listed